Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Objective:To assess the application value of one-hour post-load glucose (1hPG) for detecting prediabetes among individuals with high risk of type 2 diabetes mellitus (T2DM).Methods:The study was conducted between August 2023 and January 2024, and individuals with a high risk of T2DM were invited to receive an oral glucose tolerance test (OGTT), structural questionnaires, physical measurements, and other biochemical examinations. The fasting, one-, and two-hour glucose and insulin were tested. According to the 1hPG cut point on hyperglycemia suggested by International Diabetes Federation (IDF), normal glucose tolerance (NGT) and prediabetes were further divided into two subgroups, respectively, i.e., NGT with 1hPG<8.6 mmol/L (NGT-1hPG-normal), NGT with 1hPG≥8.6 mmol/L (NGT-1hPG-high), prediabetes with 1hPG<8.6 mmol/L (PDM-1hPG-normal), and prediabetes with 1hPG≥8.6 mmol/L (PDM-1hPG-high). The insulin release curve was drawn by the groups as above. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), and β-cell secretory function was evaluated by homeostasis model assessment for β cell function (HOMA-β)/HOMA-IR. Spearman rank correlation analysis was used to calculate the correlation coefficients among 1hPG, 2hPG and HOMA indices, and Steiger′s Z test was used to compare the difference between two correlation coefficients. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to assess the accuracy of 1hPG for detecting prediabetes. Results:A total of 2 469 subjects consisting of 1 485 men (60.1%) and 984 (39.9%) women, with a mean age of (45.76±6.20) years, of which 1 844 (74.7%) had 1hPG≥8.6 mmol/L. The prevalence of 1hPG≥8.6 mmol/L was 46.8%, 93.0% and 99.8% in individuals with NGT, prediabetes and newly diagnosed T2DM, respectively ( χ 2=763.78, P<0.001). The insulin release curve showed that insulin secretion increased rapidly in subjects with NGT-1hPG-high, and peaked at one hour, then decreased rapidly, with a significantly higher level of one- and two-hour insulin than those with NGT-1hPG-normal ( P<0.001). Compared to individuals with NGT-1hPG-normal, the counterparts with NGT-1hPG-high exhibited higher HOMA-IR and lower adjusted HOMA-β ( P<0.001). Spearman rank correlation analysis showed that the correlation coefficient of 1hPG with HOMA-IR was similar to the correlation coefficient of 2hPG with HOMA-IR (0.493 vs. 0.480, P=0.550), while the correlation of 1hPG with adjusted HOMA-β was significantly stronger than that of 2hPG (-0.692 vs. -0.587, P<0.001). Excluding patients with T2DM, according to the cut point recommended by IDF, the AUC of 1hPG≥8.6 mmol/L for detecting prediabetes was 0.731 (95% CI: 0.714-0.748), and the sensitivity and specificity were 0.930 and 0.532, respectively, with the kappa value of 0.45. Conclusion:1hPG is closely related to insulin resistance and islet function, and there′s substantial value for individuals with a high risk of T2DM to detect prediabetes by using the 1hPG cut points recommended by IDF.

ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure （CHF）. MethodsThe CHF rat model was prepared by aortic arch constriction （TAC）. Of the 72 SD rats， 8 were randomly selected as the sham operation group， where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group， the Shengxiantang low-， medium-， and high-dose groups （5.1， 10.2， 20.4 g·kg^-1）， and the trimetazidine group （6.3 mg·kg^-1）， with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage， while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of nitric oxide （NO）， endothelin （ET-1）， vascular endothelial growth factor （VEGF）， and von Willebrand factor （vWF）. Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit （ATP5D） and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin， claudin， vascular endothelial cadherin （VE-Cadherin）， and zonula occludens-1 （ZO-1）. Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group， the ejection fraction （EF） and left ventricular shortening fraction （FS） in the model group were significantly decreased （P<0.01）， while the left ventricular diastolic diameter （LVIDd）， left ventricular systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs） were significantly increased （P<0.01）. The levels of NO and VEGF were significantly decreased （P<0.01）， while the levels of ET-1 and vWF were significantly increased （P<0.01）. Under electron microscopy， the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin were significantly decreased （P<0.05， P<0.01）， and the relative density of microvessels was significantly reduced （P<0.05， P<0.01）. After intervention with Shengxiantang， the EF and FS of CHF rats significantly increased （P<0.01）， while the LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs significantly decreased （P<0.01）. The levels of NO and VEGF significantly increased （P<0.01）， while the levels of ET-1 and vWF significantly decreased （P<0.01）. Under electron microscopy， the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin significantly increased （P<0.05， P<0.01）， and the relative density of microvessels significantly increased （P<0.01）. ConclusionShengxiantang can effectively improve the cardiac function of CHF rats， reduce microvascular endothelial injury， strengthen the connection between endothelial cells， and increase microvessel density， thereby protecting myocardial microvascular injury.

ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure （CHF）. MethodsThe CHF rat model was prepared by aortic arch constriction （TAC）. Of the 72 SD rats， 8 were randomly selected as the sham operation group， where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group， the Shengxiantang low-， medium-， and high-dose groups （5.1， 10.2， 20.4 g·kg^-1）， and the trimetazidine group （6.3 mg·kg^-1）， with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage， while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of nitric oxide （NO）， endothelin （ET-1）， vascular endothelial growth factor （VEGF）， and von Willebrand factor （vWF）. Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit （ATP5D） and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin， claudin， vascular endothelial cadherin （VE-Cadherin）， and zonula occludens-1 （ZO-1）. Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group， the ejection fraction （EF） and left ventricular shortening fraction （FS） in the model group were significantly decreased （P<0.01）， while the left ventricular diastolic diameter （LVIDd）， left ventricular systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs） were significantly increased （P<0.01）. The levels of NO and VEGF were significantly decreased （P<0.01）， while the levels of ET-1 and vWF were significantly increased （P<0.01）. Under electron microscopy， the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin were significantly decreased （P<0.05， P<0.01）， and the relative density of microvessels was significantly reduced （P<0.05， P<0.01）. After intervention with Shengxiantang， the EF and FS of CHF rats significantly increased （P<0.01）， while the LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs significantly decreased （P<0.01）. The levels of NO and VEGF significantly increased （P<0.01）， while the levels of ET-1 and vWF significantly decreased （P<0.01）. Under electron microscopy， the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin significantly increased （P<0.05， P<0.01）， and the relative density of microvessels significantly increased （P<0.01）. ConclusionShengxiantang can effectively improve the cardiac function of CHF rats， reduce microvascular endothelial injury， strengthen the connection between endothelial cells， and increase microvessel density， thereby protecting myocardial microvascular injury.

Objective:To investigate the occurrence and characteristics of adverse reactions of Xuesaitong preparations, mine its coagulation disorders/bleeding risk signals, and provide references for its safe and rational use in clinic. Methods:The reports of adverse drug reactions (ADR) caused by Xuesaitong preparations from August 2003 to August 2023 in the database of Shandong Provincial Center of Adverse Drug Reaction Monitoring were collected. ADR were counted and classified using the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 26.1. Three methods, namely the reporting odds ratio (ROR), the proportional reporting ratio (PRR), and the comprehensive standard method of the Medicines and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom, were used to detect the risk signals of coagulation disorders/bleeding in using Xuesaitong preparations. Results:A total of 17 015 reports of ADR related to Xuesaitong preparations were collected, involving 9 dosage forms, in which injection dosage form accounted for 95.50% (16 250/17 015). The median age of the patients was 62 years, 44.87% of the cases were 45-64 years and 42.90% of them were 65 years and above. There were 2 217 cases of severe ADR reports, accounting for 13.03% (2 217/17 015). A total of 18 SOCs were involved, the top 3 were skin and subcutaneous tissue diseases, systemic diseases and drug administration site reactions, and neurological diseases. A total of 54 PTs were not recorded in the instructions, among which 34 were severe. Ninety-three cases about coagulation disorders/bleeding (98 times) were reported, the top 3 PTs were hematuria [24.49% (24/98)], purpura [11.22% (11/98)], and epistaxis [10.20% (10/98)]. Seven dosage forms of Xuesaitong preparations were involved, the top 3 were Xuesaitong for injection (freeze-dried) (48 cases, accounting for 51.61%), Xuesaitong injection (29 cases, accounting for 31.18%), and Xuesaitong tablets (8 cases, accounting for 8.60%). Among 93 reports of coagulation disorders/bleeding, there were 23 severe cases, accounting for 24.73%, which was significantly higher than that in other reports (12.97%), and the difference was statistically significant ( P<0.001). Sixteen PTs about coagulation disorders/bleeding were not recorded in the instructions, among which 9 were severe. The proportion of cases with onset time longer than 7 days in ADRs about coagulation disorders/bleeding was higher than that in other ADRs [22.58%(21/93) vs. 7.43%(1 258/16 922), P<0.001]. The risk signals of coagulation disorders/bleeding were mined for Xuesaitong for injection (freeze-dried), Xuesaitong injection, Xuesaitong tablets, and Xuesaitong capsules, and the risk signal density of Xuesaitong tablets was the strongest. Conclusions:The ADRs of Xuesaitong preparations involve multiple systems and organs. Among them, Xuesaitong for injection (freeze-dried), Xuesaitong injection, Xuesaitong tablets, and Xuesaitong capsules have a strong association with coagulation disorders/bleeding risks, and the proportion of severe cases is relatively high. However, the relevant risk warning information is not included in the drug instructions of some manufacturers. Medication monitoring needs to be strengthened and timely intervention should be carried out in clinic.

To summarize the problems and improvement suggestions in the implementation of GBZ158, the focus groups interview was used to interview industry experts from CDC, Occupational disease prevention and control hospital institutes, employers, third d dd鄄party technical service institutions and universities, and extract their opinions on the problems and improvement suggestions in the implementation of the standard. The operability of GBZ 158 is not strong, and there is a certain overlap with the signs in the fields of firefighting, safety and other fields. It urgently needs to be modified to comply with the reality of occupational health management in China. There are many and concentrated revision opinions on "6. Notification Cards for Occupational Hazards of Toxic Substance in Workplaces" and "7. Setting of Warning Signs in Workplaces with Toxic Substances". It is concluded that Some technical indicators of GBZ 158 have not been according with the current actual work of occupational health, and need to be revised and improved urgently, which includes enhancing the coordination with standards in the fields of firefighting and safety, supplementing normative reference documents, clarifying the setting conditions, scope of use, and application examples of warning signs of occupational hazards.

Objective:To investigate the impact of chromate exposure on pulmonary function indices in occupational populations and explore the potential role of alterations in inflammatory indicators in this process.Methods:In July 2024, A cross-sectional analysis was conducted using occupational health examination data of 30875 workers from chromate-related enterprises in Jiangsu Province in 2020 and 2021. Based on the occupational positions and whether there is chromium acid salt exposure in the occupational hazards of the research subjects over the years, they are divided into chromium acid salt exposure group and non-exposure group. For those exposed to chromium acid salts, based on job position descriptions and duration of chromium acid salt exposure, they are further categorized into intermittent exposure group and continuous exposure group; among them, the actual exposure time in the intermittent exposure group is less than half of the working shift time, and the exposure duration is less than the total working life. Pulmonary function test indicators include forced vital capacity (forced vital capacity, FVC) %, first-second forced expiratory volume (forced expiratory volume in one second, FEV 1.0) %, and the ratio of first-second forced expiratory volume to forced vital capacity (FEV 1.0/FVC) %. Peripheral blood samples from the upper limbs of the research subjects were collected on an empty stomach for routine blood tests, selecting neutrophil count, platelet count, and lymphocyte count results, calculating the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Quantitative data that meet normal distribution are expressed using Mean±SD, while variables that do not meet normal distribution are represented by M ( Q1, Q3). Categorical data are expressed using frequency or proportion (%). Linear variable comparisons between groups use t-tests. Generalized linear models were employed to assess the correlation between chromate exposure and pulmonary function indices, while mixed regression models were utilized to explore potential underlying effects. Results:Compared with the non-exposed group, the pulmonary function indices FVC (%), FEV 1.0/FVC (%), and FEV 1.0 (%) in the chromate-exposed group showed a decreasing trend ( P<0.01), indicating statistically significant differences. As the frequency of chromate exposure increased, the prevalence of pulmonary dysfunction rose. The prevalence rates of obstructive, restrictive, and mixed respiratory dysfunction among the chromate-exposed population (including intermittent exposure and continuous exposure groups) were 0.26%, 4.67%, and 0.12%, which were higher than those in the non-exposed group (0.09%, 0.84%, and 0.07%, respectively). All these differences were statistically significant ( P<0.05). After stratification by gender, a negative correlation was observed between chromate exposure and the inflammatory indicator platelet-to-lymphocyte ratio (PLR) ( P<0.05). Potential effect analysis revealed that PLR played a certain mediating role between chromate exposure and the decline in pulmonary function indices, with a mediating proportion of 2.2%. Conclusion:Chromate exposure in occupational populations may lead to a decline in pulmonary ventilatory function and alterations in peripheral blood inflammatory indicators. Inflammatory indicators may be involved in the pulmonary function decline caused by chromate exposure.

Objective:To study and compare the occupational exposure limits (OELs) of nickle and its compounds between China and foreign countries, providing scientific basis for the OEL revision of nickel and its compounds in China.Methods:From July to September 2024, Literature, OEL and related technical documents on nickel and its compounds were searched and sorted systematically at home and abroad, the main contents and technical points of OEL were extracted, and comparative analysis were conducted.Results:The earliest OELs of nickel and its compound introduced to China was maximum allowable concentration (MAC) of nickel carbonyl, and the current effective standard China was occupational exposure limits for hazardous agents in the workplace-part 1: chemical hazardous agents (GBZ 2.1-2019), covering nickel and inorganic compounds and nickel carbonyl. The former was further divided into nickel metal and insoluble compounds, and soluble nickel compounds. Based solely on the OELs of nickel and its compounds, China was relatively lower compared to developed countries such as the United States. There were significant differences in the OEL of different types of nickel and its compounds among different countries, but the OELs in China and the United Kingdom (UK) Health and Safety Executive (HSE) were basically consistent. The European Union, the United States American Conference of Governmental Industrial Hygienists (ACGIH), South Africa etal classified nickel and its compounds into respirable and inhalable based on particle size. GBZ 2.1-2019 in China labeled nickel compounds and nickel carbonyl as G1 (carcinogenic to humans), while ACGIH and National Institute for Occupational Safety and Health (NIOSH) in the United States, HSE in the UK, Australia, South Africa also labeled one or several different types of nickel and its compounds as carcinogenic.Conclusion:Based on the OELs of nickel and its compounds, China is at a relatively loose level. It is suggested to explore the possibility of future revision, considering various adverse health effects. It is suggested to conduct basic research on fibrosis induced by nickel and its compounds, providing scientific basis for revising OELs.

Objective:By systematically evaluate the implementation of GBZ 2.1, so as to provide technical basis for the future revisions of this standard.Methods:From May to October 2023, Based on the pre survey questionnaire, the semi-structured interview method was used to interviews with experts from CDC, Occupational disease prevention and control hospital institutes, employers, occupational hygiene technical service intermediaries and universities, and the inductive method was used to extract the topics and relevant suggestions.Results:Generally, GBZ 2.1 is scientific, practical, progressiveness and operable. There are still some issues such as OELs overlapping and the correspondence between Chinese and English names. The outstanding problem is the coordination with other standard contents.Conclusion:The technical indicators in GBZ 2.1 could adapt to the needs of current practical work. The coordination between standards needs to be clarified, and the new recommended content needs further promotion and exploration on how to implement it.

Objective:To analyze the changes of intestinal flora in patients with benign and malignant colorectal tumors in high altitude areas and to compare them with the normal population in low altitude areas.Methods:The clinical data of 61 patients who underwent colonoscopy in the People's Hospital of Tibet Autonomous Region from 2020 to 2022 were collected as the high altitude group.According to the colonoscopy results,they were divided into control group(29 cases),non-adenomatous polyp group(12 cases),adenoma group(10 cases),colorectal cancer group(10 cases).17 patients who had negative colonoscopy results in the Peking University Third Hospital during the same period were collected as the low altitude control group.Before bowel preparation for colonoscopy,the fecal samples were collected.Then the DNA of bacteria in the fecal samples was extracted.The V3-V4 variable region of the 16S rRNA gene was PCR amplified and high-throughput sequenced.The species diversity of fecal flora was analyzed.Results:Alpha diversity analysis showed that the species diversity of samples from the high al-titude colorectal cancer group differed statistically from that of the high altitude non-adenomatous polyp group and the low altitude control group,and the species diversity of colorectal samples from the high al-titude colorectal cancer group was higher than that of the other two groups.While beta diversity showed no significant difference among the five groups.Differences were found in phylum level analysis that the abundance of Actinobacteriota in the low altitude control group was significantly lower than those in each group of the high altitude area,while the abundance of Actinobacteriota in the colorectal cancer group was significantly lower than those in the other 3 groups of the high altitude area.Differences were found in genus level analysis that the abundance of Bacteroides,Phascclarctobacterium and Lachnoclostridium in the low altitude control group was significantly higher than those of all the groups in the high altitude area;the abundance of Blautia and Collinsella in the high altitude control group was the highest.Lacto-bacillus was not detected in the low altitude control group,while there was a highly significant difference(P＜0.05)in the level of Lactobacillus in the four groups of high altitude area,and the abundance of Lactobacillus was significantly higher in the control group than those of the other three groups.In the four groups of samples at high altitude,the abundance of Bifidobacterium decreased significantly,while the abundance of Christensenellaceae_R-7_group increased significantly.Conclusion:Compared with the high and low altitude controls,the diversity and abundance of intestinal flora in patients with colorectal benign and malignant tumors at high altitudes are different.And the abundance of species are also diffe-rent at the phylum and genus levels,suggesting that altitude factors may have some influence on intestinal flora.