su rongsheng made in china

1.Su Rongsheng, Wang Rongmei, Cao Huabin, Tang Zhaoxin et al. High copper levels promotes broiler hepatoctye mitochondrial permeability transition in vivo and in vitro. Biologcial Trace Element Research, 2011, 12 (144): 636-646.

2. Su Rongsheng, Wang Rongmei, Cao Huabin, Tang Zhaoxin et al. In vitro effect of copper chloride exposure on reactive oxygen species generation and respiratory chain complexes activities of mitochondria isolated from broile liver. Biological Trace Element Research, 2011, 12 (144): 668-677.

3.Su Rongsheng, Cao Huabin, Li Heping, Tang Zhaoxin, et al. Effect of copper on membrane permeability and respiration of mitochondria from broiler hepatocyte. Veterinary Science in China, 2007, 37 (04): 342-345. ( in Chinese)

4.Su Rongsheng, Cao Huabin, Li Heping, Tang Zhaoxin, et al. Effect of copper on hydrogen peroxide generation of mitochondria from broiler hepatocyte. Chinese Journal of Veterinary Science, 2009, 1(29): 92-96. ( in Chinese)

5.Cao Huabin, Su Rongsheng, Li Heping, Tang Zhaoxin, et al. Effect of high-copper diet on activities of respiratory chain compiexes in liver mitochondria of broilers. Chinese Veterinary Science, 2009, 1(29): 155-159. ( in Chinese)

6. Su Rongsheng, Liu Haopeng, Hu Jingjing, Tang Zhaoxin, et al. Effect of copper stress on respiration function of mitochondria from broiler hepatocyte in vitro. Chinese Journal of Veterinary Science, 2011, 10(31): 1496-1499. ( in Chinese)

7. Su Rongsheng, Yan Wenlong, Pan Jiaqiang, Tang Zhaoxin, et al. Protective Effect of glutathione on copper exposure to liver mitochondria of broilers. Chinese Journal of Veterinary Science, 2012, 32(4): 602-605. ( in Chinese)

HONG KONG (Reuters) - Jiangsu Rongsheng Heavy Industries Co Ltd has appointed Morgan Stanleyand JP Morganto finalize plans for its long-awaited IPO in Hong Kong, aiming to raise up to $1.5 billion in the fourth quarter, sources told Reuters on Tuesday.

This is Rongsheng’s latest bid to go public after it failed to raise more than $2 billion from a planned IPO in Hong Kong in 2008, mainly as a result of the global financial crisis.

Rongsheng"s early main shareholders included an Asia investment arm of Goldman Sachs, U.S. hedge fund D.E. Shaw and New Horizon, a China fund founded by the son of Chinese Premier Wen Jiabao.

The three investors sold off their stakes in Rongsheng for a profit early this year, said the sources familiar with the situation. Representatives for the banks, funds and Rongsheng all declined to comment.

Rongsheng’s revived IPO plan comes at a challenging time. Smaller domestic rival, New Century Shipbuilding, slashed its Singapore IPO in half last week, planning to raise up to $560 million from the originally planned $1.24 billion due to weak market conditions.

Given uncertainty in the global shipbuilding business environment as well as growing concerns over a huge flow of fund-raising events in Hong Kong, investment bankers suggest the potential size for Rongsheng could be $1 billion to $1.5 billion, according to the sources.

Rongsheng is seeking to tap capital markets to fund fast growth and aims to catch up with bigger state-owned rivals such as Guangzhou Shipyard International Co Ltd.

Rongsheng won a $484 million deal to build four ships for Oman Shipping Co last year. The vessels would carry exports from an iron ore pellet plant in northern Oman which is expected to begin production in the second half of 2010.

SINGAPORE, Oct 14 (Reuters) - Rongsheng Petrochemical, the trading arm of Chinese private refiner Zhejiang Petrochemical, has bought at least 5 million barrels of crude for delivery in December and January next year in preparation for starting a new crude unit by year-end, five trade sources said on Wednesday.

Rongsheng bought at least 3.5 million barrels of Upper Zakum crude from the United Arab Emirates and 1.5 million barrels of al-Shaheen crude from Qatar via a tender that closed on Tuesday, the sources said.

Rongsheng’s purchase helped absorbed some of the unsold supplies from last month as the company did not purchase any spot crude in past two months, the sources said.

Privately owned unaffiliated refineries, known as “teapots,”[3] mainly clustered in Shandong province, have been at the center of Beijing’s longtime struggle to rein in surplus refining capacity and, more recently, to cut carbon emissions. A year ago, Beijing launched its latest attempt to shutter outdated and inefficient teapots — an effort that coincides with the emergence of a new generation of independent players that are building and operating fully integrated mega-petrochemical complexes.[4]

The changing roles played by China’s independent refineries are reflected in their relations with Middle East suppliers. In the battle to ensure their profitability and very survival, smaller Chinese teapots have adopted various measures, including sopping up steeply discounted oil from Iran. Meanwhile, Middle East suppliers, notably Saudi Aramco, are seeking to lock in Chinese crude demand while pursuing new opportunities for further investments in integrated downstream projects led by both private and state-owned companies.

China’s “teapot” refineries[5] play a significant role in refining oil and account for a fifth of Chinese crude imports.[6] Historically, teapots conducted most of their business with China’s major state-owned companies, buying crude oil from and selling much of their output to them after processing it into gasoline and diesel. Though operating in the shadows of China’s giant national oil companies (NOCs),[7] teapots served as valuable swing producers — their surplus capacity called on in times of tight markets.

Yet, the Chinese government has spent the better part of two decades trying to consolidate the country’s sprawling independent refining sector by starving private operators of access to imported crude oil and targeting the smallest, least efficient plants for closure.[8] In 2011, China’s National Development and Reform Commission (NDRC) issued guidelines to eliminate small refineries to achieve economies of scale and improve efficiencies. Nevertheless, policies meant to discourage activity had the opposite effect, as most of the units that were earmarked for suspension expanded to stay open.[9]

2021 marked the start of the central government’s latest effort to consolidate and tighten supervision over the refining sector and to cap China’s overall refining capacity.[14] Besides imposing a hefty tax on imports of blending fuels, Beijing has instituted stricter tax and environmental enforcement[15] measures including: performing refinery audits and inspections;[16] conducting investigations of alleged irregular activities such as tax evasion and illegal resale of crude oil imports;[17] and imposing tighter quotas for oil product exports as China’s decarbonization efforts advance.[18]

The politics surrounding this new class of greenfield mega-refineries is important, as is their geographical distribution. Beijing’s reform strategy is focused on reducing the country’s petrochemical imports and growing its high value-added chemical business while capping crude processing capacity. The push by Beijing in this direction has been conducive to the development of privately-led mega refining and petrochemical projects, which local officials have welcomed and staunchly supported.[20]

Yet, of the three most recent major additions to China’s greenfield refinery landscape, none are in Shandong province, home to a little over half the country’s independent refining capacity. Hengli’s Changxing integrated petrochemical complex is situated in Liaoning, Zhejiang’s (ZPC) Zhoushan facility in Zhejiang, and Shenghong’s Lianyungang plant in Jiangsu.[21]

As China’s independent oil refining hub, Shandong is the bellwether for the rationalization of the country’s refinery sector. Over the years, Shandong’s teapots benefited from favorable policies such as access to cheap land and support from a local government that grew reliant on the industry for jobs and contributions to economic growth.[22] For this reason, Shandong officials had resisted strictly implementing Beijing’s directives to cull teapot refiners and turned a blind eye to practices that ensured their survival.

But with the start-up of advanced liquids-to-chemicals complexes in neighboring provinces, Shandong’s competitiveness has diminished.[23] And with pressure mounting to find new drivers for the provincial economy, Shandong officials have put in play a plan aimed at shuttering smaller capacity plants and thus clearing the way for a large-scale private sector-led refining and petrochemical complex on Yulong Island, whose construction is well underway.[24] They have also been developing compensation and worker relocation packages to cushion the impact of planned plant closures, while obtaining letters of guarantee from independent refiners pledging that they will neither resell their crude import quotas nor try to purchase such allocations.[25]

To be sure, the number of Shandong’s independent refiners is shrinking and their composition within the province and across the country is changing — with some smaller-scale units facing closure and others (e.g., Shandong Haike Group, Shandong Shouguang Luqing Petrochemical Corp, and Shandong Chambroad Group) pursuing efforts to diversify their sources of revenue by moving up the value chain. But make no mistake: China’s teapots still account for a third of China’s total refining capacity and a fifth of the country’s crude oil imports. They continue to employ creative defensive measures in the face of government and market pressures, have partnered with state-owned companies, and are deeply integrated with crucial industries downstream.[26] They are consummate survivors in a key sector that continues to evolve — and they remain too important to be driven out of the domestic market or allowed to fail.

In 2016, during the period of frenzied post-licensing crude oil importing by Chinese independents, Saudi Arabia began targeting teapots on the spot market, as did Kuwait. Iran also joined the fray, with the National Iranian Oil Company (NIOC) operating through an independent trader Trafigura to sell cargoes to Chinese independents.[27] Since then, the coming online of major new greenfield refineries such as Rongsheng ZPC and Hengli Changxing, and Shenghong, which are designed to operate using medium-sour crude, have led Middle East producers to pursue long-term supply contracts with private Chinese refiners. In 2021, the combined share of crude shipments from Saudi Arabia, UAE, Oman, and Kuwait to China’s independent refiners accounted for 32.5%, an increase of more than 8% over the previous year.[28] This is a trend that Beijing seems intent on supporting, as some bigger, more sophisticated private refiners whose business strategy aligns with President Xi’s vision have started to receive tax benefits or permissions to import larger volumes of crude directly from major producers such as Saudi Arabia.[29]

The shift in Saudi Aramco’s market strategy to focus on customer diversification has paid off in the form of valuable supply relationships with Chinese independents. And Aramco’s efforts to expand its presence in the Chinese refining market and lock in demand have dovetailed neatly with the development of China’s new greenfield refineries.[30] Over the past several years, Aramco has collaborated with both state-owned and independent refiners to develop integrated liquids-to-chemicals complexes in China. In 2018, following on the heels of an oil supply agreement, Aramco purchased a 9% stake in ZPC’s Zhoushan integrated refinery. In March of this year, Saudi Aramco and its joint venture partners, NORINCO Group and Panjin Sincen, made a final investment decision (FID) to develop a major liquids-to-chemicals facility in northeast China.[31] Also in March, Aramco and state-owned Sinopec agreed to conduct a feasibility study aimed at assessing capacity expansion of the Fujian Refining and Petrochemical Co. Ltd.’s integrated refining and chemical production complex.[32]

Commenting on the rationale for these undertakings, Mohammed Al Qahtani, Aramco’s Senior Vice-President of Downstream, stated: “China is a cornerstone of our downstream expansion strategy in Asia and an increasingly significant driver of global chemical demand.”[33] But what Al Qahtani did notsay is that the ties forged between Aramco and Chinese leading teapots (e.g., Shandong Chambroad Petrochemicals) and new liquids-to-chemicals complexes have been instrumental in Saudi Arabia regaining its position as China’s top crude oil supplier in the battle for market share with Russia.[34] Just a few short years ago, independents’ crude purchases had helped Russia gain market share at the expense of Saudi Arabia, accelerating the two exporters’ diverging fortunes in China. In fact, between 2010 and 2015, independent refiners’ imports of Eastern Siberia Pacific Ocean (ESPO) blend accounted for 92% of the growth in Russian crude deliveries to China.[35] But since then, China’s new generation of independents have played a significant role in Saudi Arabia clawing back market share and, with Beijing’s assent, have fortified their supply relationship with the Kingdom.

Smaller Chinese independents have been less fortunate, hit hard not just by tougher domestic regulation but by soaring crude oil prices.[36] US-led sanctions flowing from the war in Ukraine have compounded the pressure on teapots, which prior to the conflict had sourced about a fifth of their crude oil from Russia. Soaring oil tanker freight rates and the refusal of Chinese banks to issue letters of credit for Russian crude have choked off much of this supply, though some private refiners have compensated by using cash transfers to pay for Russian ESPO blend crude.[37]

Meanwhile, though, enticed by discounted prices Chinese independents in Shandong province have continued to scoop up sanctioned Iranian oil, especially as their domestic refining margins have thinned due to tight regulatory scrutiny. In fact, throughout the period in which Iran has been under nuclear-related sanctions, Chinese teapots have been a key outlet for Iranian oil, which they reportedly unload from reflagged vessels representing themselves as selling oil from Oman and Malaysia.[38] China Concord Petroleum Company (CCPC), a Chinese logistics firm, remained a pivotal player in the supply of sanctioned oil from Iran, even after it was blacklisted by Washington in 2019.[39] Although Chinese state refiners shun Iranian oil, at least publicly, because of US sanctions, private refiners have never stopped buying Iranian crude.[40] And in recent months, teapots have been at the forefront of the Chinese surge in crude oil imports from Iran.[41]

China’s small-scale, inefficient “first generation” teapot refiners have come under mounting market pressure, as well as closer government scrutiny and tightened regulation. Though some have already been shuttered and others face imminent closure, dozens of China’s teapots, concentrated mainly in Shandong province, continue to operate thanks to the creative defensive measures they have employed and the important role they play in local economies.

Vertical integration along the value chain has become a global trend in the petrochemical industry, specifically in refining and chemical operations. China’s drive to self-sufficiency in chemicals is a key factor powering this worldwide trend.[42] And it is the emergent “second generation” of independent refiners that it is helping make China the frontrunner in developing massive liquids-to-chemicals complexes. Following Beijing’s lead, Shandong officials appear determined to follow this trend rather than risk being left in its wake.

As Chinese private refiners’ number, size, and level of sophistication has changed, so too have their roles not just in the domestic petroleum market but in their relations with Middle East suppliers. Beijing’s import licensing and quota policies have enabled some teapot refiners to maintain profitability and others to thrive by sourcing crude oil from the Middle East. For their part, Gulf producers have found Chinese teapots to be valuable customers in the spot market in the battle for market share and, especially in the case of Aramco, in the effort to capture the growth of the Chinese domestic petrochemicals market as it expands.

Su Yu (Chinese: 粟裕; pinyin: Sù Yù; August 10, 1907 – February 5, 1984), Courtesy name Yu (裕) was a Chinese military commander, a general of the People"s Liberation Army.Mao Zedong to be among the best commanders of the PLA, only next to Peng Dehuai, Lin Biao and Liu Bocheng.Second Sino-Japanese War and in the Chinese Civil War. He commanded the East China Field Army (renamed 3rd Field Army in 1949) during the Chinese Civil War. One of his most notable accomplishments was the capture of Shanghai.

Su Yu was born in Huitong County, Hunan province on August 10, 1907 to an ethnic Dong family.Hunan Provincial 2nd Normal School at Changde for his post-secondary education.

After the breakout of the Second Sino-Japanese War in 1937, Su Yu was appointed Deputy Commander of the 2nd Detachment, and then in April 1938 commander of the Advanced Detachment of the New Fourth Army.

During the war, Su won the Cheqiao Campaign against the Japanese Army, where his troops won a victory in the first battle against the Japanese troops at Weigang. After this, he had some other campaigns in Central Jiangsu against the Japanese aggressors in Nanjing, Wuhu and Lishui.

During the Civil War, Su Yu started as the second in command of the Communists" East China Field Army, eventually becoming second in command of the Third Field Army by the end of the war.

The successes of the battle persuaded Mao Zedong to change his military strategy of the Chinese Civil War, from traditional guerrilla style warfare to a more mobile and conventional approach. In July 1946, he led 30,000 Communist troops which triumphed over 120,000 American-armed Nationalist troops in seven different engagements, captured and killed 53,000 Kuomintang soldiers and stunned the country. The Central Jiangsu Campaign was the first of many of the brilliant campaigns that defined his legacy. He was also the commander of the PLA in the famous and much propagandized Menglianggu Campaign. In this campaign, the elite Nationalist Seventy-Fourth Division was completely destroyed after Su Yu succeeded in encircling the unit.

He was the major commander during the Huaihai Campaign (November 1948 to January 1949). It was at his suggestion on January 22, 1948 that the two armies of Liu and Su followed a sudden-concentrate, sudden-disperse strategy that led to this decisive victory in late 1948, with the destruction of five Nationalist armies and the killing or capture of 550,000 Nationalist soldiers. Su"s army alone destroyed four Nationalist armies, and was the decisive force in destroying the fifth.

When the Korean War broke out in 1950, it was rumored that Su Yu was the commander that Mao wanted to lead the Chinese People"s Volunteer Army into Korea, because of his experience of commanding a large number of troops. However, because of his illness (caused by shell fragments in the 1930s), neither Su nor Lin Biao (also rumored to be sick) was able to command the CVA. In the end, Peng Dehuai was selected.

He was made a People"s Liberation Army General Staff Department in the 1950s. In his later years, he published The Memoirs of Su Yu (粟裕回忆录). He died in Beijing on February 5, 1984 at the age of 77. According to his last wish, his body was cremated and scattered to places he had fought.

Su Yu married Chu Qing (楚青) in February 1941. They had three children, all of whom joined the PLA. The eldest son Su Rongsheng (粟戎生) was born in 1942, followed by the second son Su Hansheng (粟寒生), and the youngest, a daughter Su Huining (粟惠宁), who married Chen Xiaolu (陈小鲁) in August 1975. Chen Xiaolu was the youngest son of Chen Yi who was Su Yu"s direct superior during wartime. According to Su Rongsheng, Su Yu was an extremely strict father. When Su Rongsheng was only three years old, Su Yu forced him to learn how to swim by giving him only a piece of bamboo as a float, and pushed him into the water in front of his mother, and prohibited anyone from attempting to save Su Rongsheng. Su Yu"s wife, Chu Qing was outraged and asked Su Yu angrily whether he was not worried about Su Rongsheng being drowned. But Su Yu answered that Su Rongsheng would have never learned how to swim any other way and besides, he was not being drowned. At age of 20, Su Rongsheng joined the PLA and remained in service for 45 years, rising from an ordinary soldier to a lieutenant general when he retired as the deputy commander-in-chief of Beijing Military District at age 65.

The chemical industry is central to modern China"s economy. It uses special methods to alter the structure, composition or synthesis of substances to produce new products, such as steel, plastic, and ethyl. Chemical industry provides building materials for China"s infrastructure, including subway, high-speed train, and highway.

Tu Youyou is a pharmaceutical chemist of China. She discovered qinghaosu (artemisinin) and applied to cure malaria. Qinghaosu saves millions of lives in South China, South America, Southeast Asia, and Africa. It is an important breakthrough in the medicine area last century, and Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine and Lasker Award in Clinical Medicine for her work. She is the first Chinese female to receive a Nobel Prize in Physiology or Medicine.

According to statistics, by 1984, there were actually about 9 million chemical substances in the world, of which about 43% were materials. Although the number of materials is large, if classified according to chemical composition, it can be summarized into three categories: metal materials, inorganic non-metal materials and composite materials.

The composite material is new structural material. It is characterized by a combination of volumetric strength, volumetric stiffness and corrosion resistance over metallic materials. It is composed of a matrix material such as synthetic resin, metal or ceramic, and a reinforcing material composed of inorganic or organic synthetic fibres. There are a variety of substrates and reinforcing materials so that a selective fit can be made to produce various composites with satisfactory performance, which has a broader prospect for chemical materials.

Sinochem and Shanghai Chemical Industry Institute have set up a laboratory for composite materials. The two sides will jointly develop technology, transform the results and apply in the industry of carbon fiber and its curing resins, in order to promote the technologies and products of high-performance composite materials and facilitate its industrialization and marketization. At present, this laboratory has launched a project to research and develop the spray-free carbon fiber composite material. At first, this material will be applied to new energy cars, which can not only reduce the weight of the cars but also reduce the cost of applying composite materials while improving production efficiency significantly.

Chinese companies plan to go into the specialties side of the market, and some of them already become one of the players in the market, such as Zhejiang NHU, a vitamin maker; Yantai Wanhua, an isocyanates maker; and Bairun, the leader in the Chinese flavors-and-fragrances market.

China government set up policy goals to solve the unemployment issue and boost the economy, in order to against the increasing population. The government"s policies and goals have progressed as the economy was opened up in 1978. It can be divided into three periods:

China"s chemical industry has developed over the past 40 years, from an economic backwater to the largest chemicals manufacturing economy, that consumes raw materials and energy. This change has helped hundreds of millions of Chinese out of poverty but polluted China"s air and water at the same time.

Chemical industries in China are starting to research and develop green technologies by the recommendation of the government such as the use of alternative fuels to produce chemical products. Some industries are using carbon dioxide and others naturally available to produce industrial products, fuels and other substances. For example, a specialty chemicals company called Elevance Renewable Sciences produces highly concentrated detergents by using green technology metathesis, which significantly lowers the energy consumption and minimizes pollution.

GUID: F3731A0F-5907-49F5-9B6F-5EC21F716A9BThe original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

Results: A total of 3195 patients with RA received IM (n = 1379, 43.2%) or WM (n = 1816, 56.8%). Following 1:1 propensity score matching, 1,331 eligible patients prescribed IM were compared to 1,331 matched patients prescribed WM. The GEE analysis with PSM showed that the IM was more beneficial to significantly decrease the levels of VAS, PGA and PhGA (VAS: odds ratio (OR), 0.76; 95% CI, 0.63–0.92; p = 0.004; PGA: OR, 0.76; 95% CI, 0.64–0.92; p = 0.007; and PhGA: OR, 0.77; 95% CI, 0.64, 0.93; p = 0.004), and reduce DAS28 (OR, 0.84; 95% CI, 0.73–0.98; p = 0.030) in the per-protocol population.

Conclusion: This study suggests that compare to WM, IM has advantages in improving RA-related outcomes. However, the statistical significance might not reveal significant clinical difference. Further studies should be focused on specific treatment strategies and/or disease stages.

Management of rheumatoid arthritis (RA) symptoms using Integrative medicine (IM), such as a combination of Chinese medicine (CM) and Western medicine (WM), has been widely adopted among Chinese populations (Zhao et al., 2013). With growing needs in the public and interests among investigators, number of clinical studies, including trials and reviews, have been trending up in recent decades.

Eligible patients aged 18 years or older with RA for at least 3 months who fulfilled the 1987 American College of Rheumatology (ACR) or 2010 European Alliance of Associations for Rheumatology (EULAR) diagnostic criteria diagnosed by physicians (Britsemmer et al., 2011; Kay and Upchurch, 2012). Patients were excluded if they had little or were lack of ability for self-care; confusion in diagnosis caused by acute and chronic infections; been diagnosed with severe, progressive, or uncontrolled diseases on heart, liver, kidney, gastroenterology, endocrinology, hematology, or cancer; history of joint surgery; medical history of neurological diseases or psychiatric disorders; been currently participating in clinical trials. All the participants gave written informed consent. Patients included in the study received either 1) IM or 2) WM during the treatment based on clinical considerations of physicians. The IM is defined as combined treatment of WM and CM. WM consists of pharmacotherapy for RA including steroids, NSAIDs, and DMARDs. On the other hand, CM involved Chinese herbal decoctions, or tablets/capsules composed solely of Chinese herbs and their extracts. The types of medications used by patients with RA at baseline and during follow-up were shown in Table 1. All participants were then followed up 1 year with 3-month intervals: at 3 months, 6 months, 9 months, and 12 months from the baseline visit. Since there were cases with a discrepancy between the medication at each follow-up, we defined study populations as follows to delineate the genuine effect of IM or WM treatment; intention-to-treat (ITT) and per-protocol (PP) populations. The ITT population was defined by patients who received medication at baseline. The PP population was restricted to the population who received the same medication at baseline and at follow-up.

The primary outcome was change in disease activity score 28 (DAS28) during 4 follow-up visits. The secondary outcomes included change in tender joint count (TJC), swollen joint count (SJC), morning stiffness (MS), visual analog scale (VAS), patient’s and physician’s global assessment of disease activity based on visual analogue scale (PGA, PhGA), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (Anti-CCP), simplified disease activity index (SDAI), clinical disease activity index (CDAI), health assessment questionnaire (HAQ) during 4 follow-up visits.

Continuous variables were expressed as mean (standard deviation) or medians (interquartile range, IQR), depending on the data distribution pattern. Categorical variables were described using frequencies and percentages. The Multiple Imputation (MI) by chained equations method was used to interpolate the missing data. Baseline characteristics before and after PSM were compared between IM and WM groups using the variance analysis Kruskal–Wallis rank-sum test for continuous variables and Chi-square test for categorical variables. Generalized estimating equation (GEE) models that controlled for variables were used to investigate a time trend and assess group differences in the primary outcome and secondary outcomes after PSM. This was done using a GEE autoregressive time-lag model that correlates the IM or WM on RA related clinical outcomes 1 year later. The IM or WM was used as an independent variable, each RA related clinical outcomes at baseline was used as control variable, and the corresponding continuous clinical outcomes were used as dependent variables. Significance levels were set at a 2-tailed p < 0.05. Statistical analyses were performed using R (Version 4.1.0).

A total of 3195 patients with RA received IM (n = 1379, 43.2%) or WM (n = 1816, 56.8%) and were included in the ITT population (Figure 1). During the 1-year observational period, 996 patients lost to follow up, and a comparison of baseline characteristics between the lost and follow-up groups was shown in Supplementary Table S1. 1619 (50.7%) patients continued the same medication until 12 months and were considered as the PP population. During the 1-year follow-up, a total of 1576 ITT patients changed the type of medication from WM to IM or vis versa. The comparison of baseline characteristics between the unchanged medication group and the medication changed group was shown in Supplementary Table S2. The frequency of missing baseline information of the unchanged medication patients was 38 (1.19%) cells (Supplementary Table S3). Throughout the study, we recorded abnormal values from the patients based on their laboratory test results. However, we are not able to judge whether the abnormalities were caused by the disease or/and the treatments. In the study, no serious adverse event was observed. There was no direct evidence showing a significant difference in the rate of self-reporting adverse events in the PP population between the two groups (p = 0.713), which was 1.35% and 1.72% in the WM and IM groups, respectively.

In the unmatched groups (1,816 patients treated by WM compared to 1,379 patients treated by IM), the IM group was older (mean age 62.02 versus 60.34 years, p < 0.001) and had a higher level of BMI (22.09 versus 21.89 kg/m2, p = 0.036) compared to the WM group in the ITT population (Supplementary Table S4). Compared to the WM group, the IM group had similar proportion of males, family history and operation history of RI-related. The IM group had higher rates of smoking and drinking. 256 (18.6%) patients reported at least one comorbidity in the IM group which was slightly higher than the WM group (p = 0.044). However, the prevalence of hypertension and diabetes was similar in both groups. The median duration of RA of both groups was about 6 years.

Following 1:1 propensity score matching, 1,331 eligible patients prescribed IM were compared to 1,331 matched patients prescribed WM. After matching, the demographic and clinical characteristics of both groups were well balanced (Supplementary Table S4).

Comparisons of treatment groups in the PP population before PSM showed that the IM group were older than the WM group (mean age 64.66 versus 60.96 years, p < 0.001). The proportions of male patients were about 19% in both groups. 56 (5.4%) patients in the WM group had family history of RI-related which was higher than the IM group (p = 0.018). Patients in the WM group had higher smoking rates (2.4% versus 1.0%, p = 0.050). 553 eligible patients prescribed IM were compared to 553 matched patients prescribed WM after PSM. No statistically significant differences were found in baseline variables after matching between groups (Table 2).

Changes in clinical manifestations measures of RA in the ITT and PP population from baseline to 4 follow-up visits were shown in Supplementary Table S5 and Table 3, respectively. The comparison in different rheumatoid arthritis clinical manifestations between baseline and visit 4 in medication changed group was shown in Supplementary Table S6. In the ITT population, the time × group interaction for all outcomes was not significant (p > 0.05). Figure 2 shows the changes of outcomes in six domains related to RA, including joint, morning stiffness, and pain, between baseline and the fourth follow-up, and overall decreased in both IM and WM group in PP population. The results indicated a significant time × group interaction for MS (p = 0.049), PGA (p = 0.049), and PhGA (p = 0.047), indicating that the scores for these three domains in the 2 groups had different trends over the 5 time points. Compared with the WM, the IM significantly decreased the levels of VAS, PGA and PhGA in the PP analysis (VAS: odds ratio (OR), 0.76; 95%CI, 0.63–0.92; p = 0.004; PGA: OR, 0.76; 95% CI, 0.64–0.92; p = 0.007; and PhGA: OR, 0.77; 95% CI, 0.64, 0.93; p = 0.004).

PP, per-protocol; IM, integrative medicine; WM, western medicine; IQR, interquartile range; TJC, tender joint court; SJC, swollen joint count; MS, morning stiffness; VAS, visual analog scale; PGA, patient’s global assessment of disease activity; PhGA, physician’s global assessment of disease activity; ESR, erythrocyte sedimentation rate; CRP, c-reaction protein; RF, rheumatoid factor; Anti-CCP, anti-cyclic citrullinated peptide; DAS28, disease activity score 28; SDAI, simplified disease activity index; CDAI, clinical disease activity index; HAQ, health assessment questionnaire.

Box plots of changes in joint, morning stiffness, and pain outcomes during the first year of follow-up in PP population. IM: Integrative medicine, WM: Western medicine, PGA, PhGA, patient’s and doctor’s global assessment of disease activity based on visual analogue scale.

The variation patterns of laboratory outcomes in the IM and WM groups in PP population at baseline and follow-up were shown in Figure 3. The average level of RA related laboratory indicators in each domain in both two groups gradually decreased over time (Table 3). The result indicated a significant time × group interaction for ESR (p = 0.032). The ESR level of patients in the IM and WM groups decreased gradually from baseline 28 mm/h to 21 and 22 mm/h, respectively. However, the level of CRP, RF and CCP reduced by IM was not significantly higher than that of WM (p > 0.05).

Box plots of changes in laboratory outcomes during the first year of follow-up in PP population. IM: Integrative medicine, WM: Western medicine, PGA, PhGA, patient’s and doctor’s global assessment of disease activity based on visual analogue scale.

Box plots of changes in Composite outcomes during the first year of follow-up in PP population. IM: Integrative medicine, WM: Western medicine, PGA, PhGA, patient’s and doctor’s global assessment of disease activity based on visual analogue scale.

Biologically, the involvement of Chinese herbal medicine induces multiple treatment pathways and mechanisms especially single herb can contain various kinds of active ingredients targeting RA-related receptors and biomarkers (Chen et al., 2004; van der Greef et al., 2010; Seca and Franconi, 2018). With human clinical trials and animal studies suggested the efficacy and safety of IM with Chinese herbal medicine and their extractions (Liu et al., 2018; Wang et al., 2019), IM approaches are expected to motivate improvements in RA treatments strategies and outcomes. Moreover, as biological agents for rheumatoid arthritis are gradually under consideration for national health insurance coverage, we look forward to investigating the role of biological agents in IM treatment strategies in future studies.

Prevalence of RA is estimated to be 0.2–0.3% in China with approximately 3-million patients (Zeng et al., 2008). Data provided by this perspective cohort will play a key role in reflection of the health service in China by revealing the medical treatments given to the RA patients. In recent years, IM approaches have been receiving attention globally not only among the patients, but also among physicians, researchers, and decision-makers. However, in many diseases, the benefits brought by IM over WM are still unclear. As a result, we hope our analysis could facilitate other teams/nations to carry out further IM-related research for RA in particular through clinical trials with investigation of underlying treatment mechanisms, and eventually, facilitate development of corresponding IM clinical practice guidelines.

This study suggests that compare to WM, IM has advantages in improving RA-related outcomes. However, the statistical significance might not reveal significant clinical difference. Further studies should be focused on specific treatment strategies and/or disease stages.

We thank all the patients participated for data contribution and our colleagues for their dedicated work on the cohort. We would also like to thank Shu Yang, School of Intelligent Medicine, Chengdu University of Traditional Chinese Medicine, for the support in statistical analysis.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

This work was supported by following funding programs: Leading Talents in Shanghai; Shanghai Municipal Health Commission, and East China Region based Chinese and Western Medicine Joint Disease Specialist Alliance [ZY (2021-2023)-0302]; The 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab), [No: 2020B1212030006]; and Science and Technology Commission of Shanghai Municipality [STCSM Q12 19401934600].

RA, Rheumatoid arthritis; IM, Integrative medicine; CM, Chinese medicine; WM, Western medicine; NSAIDs, non-steroidal anti-inflammatory drugs; DMARDs, disease-modifying antirheumatic drugs; ACR, American College of Rheumatology; EULAR, European Alliance of Associations for Rheumatology; ITT, intention-to-treat; PP, per-protocol; BMI, body mass index; RI, rheumatic immunity; PSM, propensity score matching; DAS28, disease activity score 28; TJC, tender joint count; SJC, swollen joint count; MS, morning stiffness; VAS, visual analog scale; PGA, patient’s global assessment of disease activity; PhGA, physician’s global assessment of disease activity; ESR, erythrocyte sedimentation rate; CRP, c-reactive protein; RF, rheumatoid factor; Anti-CCP, anti-cyclic citrullinated peptide; SDAI, simplified disease activity index; CDAI, clinical disease activity index; HAQ, health assessment questionnaire; MI, multiple imputation.

Britsemmer K., Ursum J., Gerritsen M., van Tuyl L. H., van Schaardenburg D., van Schaardenburg D. (2011). Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: Slight improvement over the 1987 ACR criteria. Ann. Rheum. Dis.

Liu W., Zhang Y., Zhu W., Ma C., Ruan J., Long H., et al. (2018). Sinomenine inhibits the progression of rheumatoid arthritis by regulating the secretion of inflammatory cytokines and monocyte/macrophage subsets. Front. Immunol.

Zhang C., Jiang M., He X. J., Lu A. P. (2015). Clinical trials of integrative medicine for rheumatoid arthritis: Issues and recommendations. Chin. J. Integr. Med.

Zhao J., Zha Q., Jiang M., Cao H., Lu A. (2013). Expert consensus on the treatment of rheumatoid arthritis with Chinese patent medicines. J. Altern. Complement. Med.

(31 March 2015, Hong Kong) - China Rongsheng Heavy Industries Group Holdings Limited ("China Rongsheng Heavy Industries", the "Company" or "We", and together with its subsidiaries, the "Group"; stock code: 01101.HK) announced its audited annual results for the twelve months ended 31 December 2014 (the "Period").

Launched a fresh start, China Rongsheng Heavy Industries implemented its strategy of business transformation in 2014 and completed the acquisition of oilfield project in Kyrgyzstan in September. We are proactively transforming into an oil and natural gas exploitation and production operator.

Meanwhile, we demonstrated the strong production capacity of our shipbuilding facilities and outstanding technical expertise of the Group. Our shipbuilding segment has delivered 11 vessels, with a total volume of 2,059,660 DWT, successfully in 2014. More proactively sorting and optimising our order book, we decisively reduced the number of vessels under construction and cancelled some shipbuilding orders. We believe this action not only was in alignment with the Group"s strategic plan to optimize the production and operation of its shipbuilding business during the Period, but also effectively reduced our burden on working capital and the credit risk of our order book, in spite of the fact that we have recorded a relatively larger amount of comprehensive net loss for the Period and a reversal of revenue of RMB4,530.7 solely resulted from the cancellation of shipbuilding contracts.

non-cash provisions and impairments, supporting us to strive for a strategic transformation towards energy sector and being well-equipped for future challenges.

In 2014, we sorted and optimised our order book by reducing the number of vessels under construction and cancelling some shipbuilding orders. We negotiated proactively with ship owners and reached agreement with them on certain orders on hand, resulting in the cancellation, revision and variation of a number of shipbuilding contracts. We believe that this action will reduce our burden on working capital and effectively reduce the credit risk of our order book. Thus, the shipbuilding segment of the Company recorded a negative revenue of RMB3,891.4 million which is mainly attribute to the reversal of revenue from cancellation of shipbuilding contracts for the Period.

As at 31 December 2014, our total orders on hand consisted of 35 vessels, representing a total volume of approximately 4,203,700 DWT with a total contract value of approximately USD1,668.4 million. They included 18 Panamax bulk carriers, 1 very large ore carrier, 1 Panamax crude oil tanker, 12 Suezmax crude oil tankers, 1 very large crude oil carrier, and 2 7,000-TEU containerships.

We utilised existing facilities and technical expertise to construct the No. 28 and No. 29 steel caisson projects of the Shanghai Yangtze River Bridge and successfully delivered them during the Period, demonstrating our ability in building non-vessel steel structures and securing new sources of revenue. The No. 29 steel caisson, weighing approximately 15,000 tons, is the largest steel caisson of its kind in the world.

On 11 September 2014, we completed the acquisition of 60% interest in the project (the "Kyrgyzstan Project") involving four oilfields located in the Fergana Valley of the Republic of Kyrgyzstan, which marked our breakthrough in the energy exploration and development sector. The Kyrgyzstan Project comprises of five oilfield zones namely, Maili-Su IV, Eastern Izbaskent, Izbaskent, Changyrtash and Chigirchik. The first three oilfield zones are located at the northeastern part of the Fergana Valley while the latter two are located at the Southeastern part of Fergana Valley. The total area covered by these five fields is approximately 545 square kilometres. The remaining recoverable reserves is estimated to be around 638 million barrels (MMbbl) of oil. Under the agreements entered into with the national oil company of Kyrgyzstan, Kbprb3>KepHeq:nera3 ("Kyrgyzjer Neftegaz" Limited Liability Company*), our indirect wholly-owned subsidiary was granted rights to cooperate with the national oil company of Kyrgyzstan in the operation of the five oilfields zones.

From 11 September 2014 to 31 December 2014, we have made satisfactory progress in the project. As at 31 December 2014, we had successfully completed drilling of 10 wells and had produced 16,260 barrels (bbl) of light crude oil, our daily production rate being about 252 bbl of light crude oil, even though only part of the oil wells were in operation. After initial drilling and production, we further understood and acknowledgedt the geological condition of the project. We will continue the process of perforating, testing and fracturing of the new wells to ramp up production. Since the project is still at the initial development stage, the sales of oil has not been reflected as revenue for the Period under relevant accounting treatment.

We have taken certain measures to mitigate the liquidity pressure and to improve financial position. In 2014, we completed issue of convertible bonds amounted to a total net proceeds of HKD3,985 million to strategic investors. In October, we has signed debt optimization framework agreements with a syndicate of domestic banks in Hefei of

Anhui Province. Plus, the debt optimization framework agreement we have entered into with a syndicate formed by more than ten banks in Jiangsu Province, including Bank of China, The Export-Import Bank of China and China Minsheng Bank, such measures effectively mitigated liquidity pressure of the Company.

Global economic recovery will remain a challenging course in 2015. Freight fees will remain at lower levels as any fundamental improvements to the situation of surplus capacity in the shipping market will be unlikely. It is well within expectations that the China"s shipbuilding industry will generally enter into a stage of structural realignment and rebuilding of strengths.

In September 2014, we obtained the rights to co-operate with the national oil company of Kyrgyzstan in respect of five oilfield zones in Kyrgyzstan by way of the allotment of shares as consideration. Central Asia is a region subject mainly to the influence of Russia, whose export oil prices have not plunged in tandem with international oil prices and have remained apart from the international price level. Local domestic oil prices of Kyrgyzstan have not changed significantly despite the dramatic decline in international oil prices. In view of the low costs and stable local oil prices, we are of the view that, under the current adverse market conditions of the shipbuilding industry, exposure to the energy sector will enable us to diversify our operations and broaden our source of revenue, as well as drive our active transformation from a manufacturer to a supplier in the energy service sector, thereby enhancing contributions to the overall interests of our shareholders.

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The intestine is the main organ for nutrient digestion and absorption and colonizes trillions of microorganisms (Yang et al., 2018). According to statistics, the human intestine inhabits over 1014 microorganisms, about 10 times the total amount of human cells (Koboziev et al., 2014). Mounting evidence indicated that gut microbiota played essential roles in immunity, intestinal homeostasis, and epithelium differentiation (Liu et al., 2020; Xiang et al., 2020). Moreover, numerous investigations also revealed the positive regulation roles of gut microbiota in intestinal barrier function, metabolism, and host health (Cani and Delzenne, 2009; Dong et al., 2020). Some bacteria have the ability to restrict the proliferation of pathogenic and opportunistic pathogens in the intestine by producing beneficial metabolites, which was considered a vital barrier against pathogen infection (Wang et al., 2018a). Although intestinal microorganisms reside in the intestine, they may cause systemic effects. Numerous studies provided supporting evidence that gut microbiota was a central or driving factor of many diseases, injuring both near and far organ systems (Acharya and Bajaj, 2021). Gut microbial alterations may extend their detrimental influences beyond the intestine and impair liver and brain (Albhaisi et al., 2020). However, gut microbial homeostasis is easily affected by many factors, such as stress, antibiotics, heavy metal, and pesticide (Kakade et al., 2020). Early studies revealed that gut microbial alternations were associated with many diseases, including diarrhea, diabetes, obesity, and even colorectal cancer (Frazier et al., 2011; Wang et al., 2018b).

Thiram (tetramethyl thiuram disulfide), a broad-spectrum antibacterial pesticide, is widely used in field crops, such as wheat, corn, cotton, and multiple vegetables (Zhang et al., 2018). However, thiram has been demonstrated to be toxic to many animals, including chickens, goats, mice, and fish (Oruc, 2010; Huang et al., 2018). Previous research has indicated that thiram significantly could stimulate the respiratory tract, skin, and gastrointestinal mucosa and inhibit the formation of white blood cells (Walia et al., 2009). Moreover, long-term thiram exposure also caused dysfunction of the central nervous system, internal organs, and endocrine system (Oruc, 2010). Recent studies on thiram toxicity demonstrated that thiram exposure could decrease the quality of the chicken and induce lipid metabolism disorder (Kong et al., 2020). Additionally, other studies indicated that exposure to thiram significantly altered the biochemical indices of liver function and induced bone disease by inhibiting the development of chondrocytes (Mehmood et al., 2019). However, the relationship between thiram exposure and gut microbiota of chickens remains scarce. Herein, we dissected the shifts of gut microbiota in thiram-induced chickens.

The collected intestinal and liver tissues were fixed immediately in 4% paraformaldehyde for subsequently preparing histological sections. The specific methods and details of hematoxylin and eosin (H&E) stains were conducted according to previous research (Mehmood et al., 2019).

Total RNA of liver was extracted using TRIzol reagent as per the efficient RNA extraction method. Subsequently, the isolated RNA was reverse-transcribed into cDNA based on the manufacturer"s guidelines. The RT-qPCR was conducted in Step One-PlusTM Real-Time PCR System (Applied Biosystems). The reaction condition and mixture specification were determined as described previously (Mehmood et al., 2019). The relative expression of each gene was calculated with 2−ΔΔCT method and normalized to GAPDH expression. Related primers used in this experiment, such as Atg5, Bak1, Bax, Bcl2, Beclin1, Casp3, Lc3b, and P53, are shown in Supplementary Table S1.

The collected liver was homogenized and centrifuged at 12,000 rpm for 10 min to obtain the supernatant for evaluating total protein concentration. The total protein concentration was assessed by the Coomassie Brilliant Blue g-250 method. Western blot analysis was performed based on the method of previous studies. The main antibodies used in this study were Atg5, Bax, Cytc, Beclin1, Lc3b, and P62. Data were indicated as the protein normalized to GAPDH expression.

All frozen intestinal samples were thawed on ice and homogenized, and the homogenized samples (approximately 200 mg) of each intestinal segment were applied to total genomic DNA extraction based on the manufacturer"s protocol. Subsequently, the quality evaluation (integrality, purity, and concentration) of extracted DNA was performed. The specific primers (338F: ACTCCTACGGGAGGCAGCA and 806R: GGACTACHVGGGTWTCTAAT) with adaptors synthesized as per the 16S rRNA conserved regions were used to amplify the V3/V4 hypervariable regions. PCR amplification procedure was performed in triplicates, and reaction conditions and volume were based on previous studies. Afterward, the obtained amplified products were subjected to quality evaluation, recycle target fragment, fluorescent quantitation, and purification. The final libraries were subjected to sequencing following the standard protocols.

The obtained raw reads were subjected to filter, identify, and remove primer sequences by Trimmomatic (v0.33) and Cutadapt software (1.9.1) to obtain clean reads that do not contain primer sequences. The clean reads of each intestinal sample were performed double-ended sequence splicing using Usearch software (v10), and then the spliced data were filtered by length based on the length range of different areas. The final effective reads were obtained after identifying and removing the chimera sequence using UCHIME software (v4.2). The obtained effective reads were clustered as operational taxonomic units (OTUs) as per 97% similarity. Multiple diversity indices were generated according to the abundance distribution of OTUs in different samples to evaluate the gut microbial diversity. PCoA was employed to visualize the gut microbial difference between control and thiram-exposure groups. Differentially represented microbial taxa between both groups were analyzed utilizing the LEfSe and Metastats analysis. GraphPad Prism (v8.0) was used for performing statistical analysis. Probability values (means ± SD) <0.05 were considered statistically significant.

The histopathological alterations in the intestine and liver are shown in Figure 1. HE staining indicated that the intestinal structures in controls were integrated with clear borders, whereas those in thiram-treated chickens were arranged loosely, irregularly, and disorderly (Figures 1A1,A2,B1,B2). Additionally, the liver tissues in the control chickens were displayed as regular and normal structures. However, thiram exposure caused a decrease in glycogen vacuoles of hepatocytes (Figures 1C1,C2,D1,D2).

Figure 1. Thiram exposure caused intestinal and liver injury. (A1,A2,B1,B2) Histopathological observation in intestinal tissues of the control group and thiram-treated group. (C1,C2,D1,D2) Histopathological observation in liver tissues of the control group and thiram-treated group. (E) Changes in gene expression related to liver apoptosis and autophagy. (F) Changes in protein expression related to liver apoptosis and autophagy.

To investigate the effect of thiram on liver autophagy and apoptosis, we detected the expression of genes related to autophagy and apoptosis in the liver by RT-qPCR analysis. Results indicated that thiram exposure significantly affected autophagy and apoptosis-related gene expression. As shown in Figure 1E, apoptosis-related gene expressions including Bax and Bcl2 were dramatically increased in the thiram-treated group as compared to the control group, whereas no significant differences in P53, Casp3, and Bak1 levels were found between both groups. Moreover, the mRNA levels of apoptosis-related genes, such as Beclin1 in the thiram-treated group, were significantly increased via comparing the control group, but no obvious differences in Atg5 and Lc3b levels were observed between both groups. Similarly, the results of western blot also indicated that the expression of Bax was significantly improved in the thiram-treated group in comparison with the control group (Figure 1F).

In this microbiome investigation, six ileal samples were conducted amplicon sequencing and 480,338 (CI = 239,765, TI = 240,573) raw sequences were collected (Table 1). After quality evaluation and data optimization, we totally acquired 458,546 (CI = 228,428, TI = 230,118) effective reads, with a median read count of 76,424 (ranging from 75,852 to 77,136) per sample. Both rarefaction and rank abundance curves of each sample supported the adequacy of the sampling efforts (Figures 2A–C). In addition, a total quantity of 333 OTUs was recognized and 199 OTUs were shared by both groups, which together made up 59.76% of the overall OTUs (Figure 2D). Moreover, 77 and 57 OTUs were uniquely recognized in CI and TI, respectively (Figures 2E,F).

Figure 2. Thiram exposure changed the gut microbial composition and diversity of chickens. (A,B) Rarefaction curves. (C) Rank abundance curve. (D–F) Venn diagrams. (G–I) Chao1, ACE, and Simpson indices were employed to evaluate gut microbial alpha diversity. (J) PCoA map based on the unweighted UniFrac distance. (K) Clustering analysis. (L,M) Relative proportion of preponderant bacteria at the phylum and genus levels.

To further dissect the gut microbial alternations during thiram exposure, we calculated the alpha and beta diversity in the microbial community. There were statistically significant differences in the Chao1 (224.95 ± 9.63 vs. 166.64 ± 1.14, p = 0.0039) and ACE (225.6421 ± 5.8365 vs. 162.4799 ± 1.0765, p = 0.0004) indices, whereas the Simpson index (0.392 ± 0.05 vs. 0.4916 ± 0.0791, p = 0.3469) was not dramatically different between the CI and TI (Figures 2G–I). Statistical analysis of alpha diversity showed that thiram exposure significantly decreased the gut microbial richness of chickens but had no effect on the microbial diversity. Moreover, the beta diversity reflecting the differences between intergroup and intra-group individuals was evaluated using PCoA and UPGMA tree. PCoA plots revealed aggregation of intra-group samples, but a separation of samples in different groups, which was consistent with the UPGMA tree, implying that the gut microbial principal component was strongly affected by the thiram exposure (Figures 2J,K).

The relative proportions of preponderant taxa at different levels were assessed by microbial taxon assignment, and significant variations in the gut microbial community of CI and TI were observed. There were nine phyla identified in six samples, varying from seven to nine phyla per sample. The phyla Proteobacteria (76.94, 71.60%), Firmicutes (22.52, 25.30%), and Actinobacteria (0.37, 1.74%) were the three most preponderant phyla in the CI and TI regardless of health status, which accounted for over 98% of all bacterial taxa (Figure 2L). Other bacterial phyla including Gemmatimonadetes (0.0018, 0.088%), Fusobacteria (0.0063, 0.069%), and Epsilonbacteraeota (0.00090, 0.021%) in CI and TI were indicated with lower abundances. To further dissect the influence of thiram exposure on taxonomic compositions, 168 genera were totally identified in the bacterial populations. Among them, Escherichia–Shigella (76.57%) was the most prevalent genus in the CI, followed by Candidatus Arthromitus (11.25%) and Enterococcus (3.15%) (Figure 2M). Moreover, Escherichia–Shigella (41.99%), Acinetobacter (26.63%), and Candidatus Arthromitus (11.07%) were abundantly present in the TI, which together made up approximately 80% of the bacterial composition. The heatmap reflecting the genus-level cluster analysis displayed the bacterial distribution in different samples and revealed the alternations in bacterial compositions during thiram exposure (Figure 3).

To further determine the shifts in microbial compositions of chickens during thiram exposure, Metastats analysis was conducted to characterize the differences in the gut microbiota of both groups. At the phylum level, the abundances of Actinobacteria (P < 0.01) and Acidobacteria (P < 0.05) in the TI group were dramatically dominant than in the CI group (Figure 4). At the genus level, 18 genera were totally detected to be significantly different between CI and TI groups. Among them, the relative richness of eight genera (Lachnospiraceae_FCS020_group, Oribacterium, Tyzzerella_4, Lachnospiraceae_UCG-008, Marvinbryantia, Ruminiclostridium, Lachnospiraceae_UCG-004, and Ruminococcus_2) dramatically reduced, whereas the relative abundances of 10 genera (Prevotella_7, Pseudochrobactrum, Aerococcus, uncultured bacterium_f_Beggiatoaceae, Arthrobacter, Pseudomonas, Rummeliibacillus, Lysobacter, Sphingomonas, and uncultured_bacterium_f_Xanthobacteraceae) significantly increased during thiram exposure. Among decreased bacterial genera, seven genera (Lachnospiraceae_FCS020_group, Oribacterium, Tyzzerella_4, Lachnospiraceae_UCG-008, Marvinbryantia, Lachnospiraceae_UCG-004, and Ruminococcus_2) even cannot be found in the gut microbiota of thiram-induced chicken. Given this discriminant analysis could not distinguish the dominant taxon, LEfSe was employed for generating a cladogram to identify the specific bacteria related to thiram exposure (Figure 5). We also found that Anaerofilum, Macrococcus, and Faecalibacterium were the most preponderant bacteria in the CI group, whereas Lactobacillus, Klebsiella, and Bradyrhizobium were observably overrepresented in the TI group.

Figure 4. Significant shifts in the gut microbial compositions during thiram exposure. Metastats analysis displayed microbial changes between both groups. All data were represented as mean ± SD. *p < 0.05, **p < 0.01.

Figure 5. Cladogram showing the phylogenetic distribution of gut microbial community related to the control and thiram-exposure groups (A). LDA scores > 2 were considered statistically significant (B).

Pesticides have been extensively used in agricultural production, but they may be accumulated and enriched in multiple ecosystems, posing a great threat to food safety and public health (Fu et al., 2018; Xu et al., 2020). Early investigations revealed that thiram exposure could cause decreased growth performance, liver toxicity, oxidative damage, and even osteogenesis disorders in chickens, but its potential influence on gut microbiota, apoptosis, and autophagy in chickens remains uncertain (Mehmood et al., 2019; Zhang et al., 2019). Here, the thiram poisoning model was constructed to investigate its influence on gut microbiota, apoptos