ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg^-1）， medium-dose TFA （TFA-M， 54 mg·kg^-1）， high-dose TFA （TFA-H， 108 mg·kg^-1）， and losartan potassium （LST， 4.5 mg·kg^-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl₄ was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E₂ （PGE₂）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE₂ levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE₂ levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B₄， leukotriene D₄， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.

OBJECTIVE To explore the mechanism of total flavonoids from stem and leaf of Scutellaria baicalensis in treating ulcerative colitis based on network pharmacology and animal experiments. METHODS The total flavonoids in stem and leaves of Scutellaria baicalensis were reviewed in literature, the corres ponding targets of total flavonoids in stem and leaves of Scutellaria baicalensis were retrieved by TCM systematic pharmacology database and analysis platform(TCMSP), and the related targets of ulcerative colitis were collected by GeneCards database. The corres ponding targets of total flavonoids from the stem and leaves of Scutellaria baicalensis and those related to ulcerative colitis were in put into Venny 2.1 mapping software to obtain the intersection targets, which were uploaded to STRING data platform for the construction of protein-protein interaction network. The gene ontology(GO) functions and the Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment were analyzed using the DAVID data platform jointly. The network pharmacological results were verified in a mouse model of ulcerative colitis induced by 3% DSS. RESULTS The results of network pharmacology showed that there were 69 related targets, 1383 related targets in ulcerative colitis and 24 overlapping targets in 7 components of total flavonoids from stem and leaves of Scutellaria baicalae. GO and KEGG pathway enrichment analysis were conducted to obtain the potential pathways of total flavonoids from stem and leaves of Scutellaria baicalensis in the treatment of ulcerative effects, including aryl hydrocarbon receptor(AhR), Th17 cell differentiation, T cell receptor, etc. The results of 3% DSS induced ulcerative colitis mouse model showed that compared with the model group, total flavonoids of scutellaria scutellaria stem and leaf significantly decreased the levels of MPO, TNF-α, IL-1β and IL-17 and increased levels of IL-10 and IL-22 with statistical difference, and restored the colon length of mice. Activated the AhR pathway and its CYP1A1 and CYP1B1 targets to promote the expression of anti-inflammatory factor IL-22, and repair the intestinal barrier by activating ZO-1 proteins. CONCLUSION Total flavonoids from stem and leaf of Scutellaria scutellaria can synergistically treat ulcerative colitis based on the characteristics of multi-component, multi-target and multi-pathway.

OBJECTIVE: To compile the Chinese Musculoskeletal Questionnaire(CMQ) and test its reliability and validity. METHODS: The initial CMQ was formed through studying literatures, interviewing professional workers who have work-related musculoskeletal disorders(WMSDs) and investigation with occupational health and ergonomics experts. Then, 436 and 443 manufacturing workers were selected as prediction and verification samples respectively by convensence sampling method. The reliability and validity of the CMQ were tested by item analysis, exploratory factor analysis and confirmatory factor analysis. RESULTS: i) The CMQ composed of 48 items with item analysis. ii) Nine common factors of CMQ were extracted using exploratory factor analysis, which explained 70.721% of WMSDs variance. iii) The results of confirmatory factor analysis showed that the ratio of chi-square to degree of freedom was 3.380, the comparative fit index was 0.781, the Tucker-Lewis index was 0.764, the root mean square error of approximation was 0.073, and the standardized root mean square residual was 0.068. iv) The results showed that the item reliabilities of the 9 common factors of CMQ such as upper and lower limbs posture load, neck posture load, back posture load, job demand, social support, job control, job environment, job system and job facilities were 0.205-0.841, the composite reliabilities were 0.545-0.894, and the convergence efficiencies were 0.377-0.834. The correlation coefficients between the common factors were less than its square root of the convergence validities. CONCLUSION: The CMQ has good reliability and validity, and is a reliable and effective tool for evaluating WMSDs.

OBJECTIVE: To investigate the prevalence of lower extremity work-related musculoskeletal disorders(WMSDs) among manufacturing workers, and to explore the association of lower extremity WMSDs and different types of working. METHODS: A total of 7 908 workers were selected as study subjects from four manufacturing factories in China using the cluster sampling method. The Musculoskeletal Disorders Investigating Questionnaire was adopted to investigate the prevalence of lower extremity WMSDs and the distribution of types of working. The prevalence ratio(PR) of WMSDs, calculated by log-binomial model, was used to estimate the correlation of WMSDs in different parts of lower extremity. The multi-factor logistic regression was used to analyze the association of lower extremity WMSDs and different types of working. RESULTS: The total annual prevalence of lower extremity WMSDs was 41.0%(3 241/7 908) among manufacturing workers. The annual prevalence of WMSDs of different parts in lower extremity from high to low were knee(29.5%), ankle/foot(23.9%) and hip/thigh(16.7%). The correlation of WMSDs of the three parts in lower extremity was close, and the range of PR values was 2.21-3.88. The result of logistic regression analysis showed that the workers who frequently sat for long periods had higher risk of lower extremity WMSDs than those who never/rarely sat for long periods(odds ratio=1.39, P<0.01). The higher the frequency of standing, kneeling/squatting for long periods, carrying heavy loads ≥5 kg and driving, the higher the risk of lower extremity WMSDs(the odds ratios were 1.33, 1.41, 1.16 and 1.12, respectively, P<0.01). CONCLUSION: The prevalence of lower extremity WMSDs was relatively high among manufacturing workers. There is a dose-effect relationship between the types of working and lower extremity WMSDs.

OBJECTIVE: To analyze the prevalence of work-related musculoskeletal disorders(WMSDs) among dentists and explore its influencing factors. METHODS: A total of 455 dentists from 9 medical organizations of Beijing and Fuzhou cities were selected as study subjects. The disease occurrence and mental workload were investigated using China Musculoskeletal Disorders Questionnaire and Subjective Workload Assessment Technique. The influencing factors of WMSDs were analyzed by multivariate logistic regression. RESULTS: The total prevalence of WMSDs was 58.9%(268/455) among dentists. The top three body parts of WMSDs were neck(41.5%), shoulder(33.6%) and lower back(28.1%). The median of mental workload score was 58. Multivariate logistic regression analysis results indicated that female dentists showed a higher risk than male dentists(P<0.01) after excluding the influence of confounding factors. The higher the length of service, the higher their risk for WMSDs(P<0.01). Dentists who hold their heads sideways for long time, bent frequently, and use vibrating tools had relatively high risks of developing WMSDs(P<0.01). Dentists who use armchairs had a relatively low risk of WMSDs(P<0.01). There was no correlation between the mental workload and the prevalence of WMSDs in dentists(P>0.05). CONCLUSION: The prevalence of WMSDs among dentists is high. Individual factors, awkward posture and using vibrating tools are risk factors of WMSDs among dentists.Armchair use can help reduce the risk of WMSDs.

Objective: To investigate the visual application of the CiteSpace software in the field of work-related musculoskeletal disorders (WMSDs) . Methods: The literature on WMSDs research, published from 1991 to 2017, was retrieved in Web of Science database. The CiteSpace 5.2 was used to make visualization analysis on the hotspots and tendency of the keywords, authors, countries (regions) and research institutes in relevant literature. Results: A total of 3224 literatures were included in the analysis. The amount of the literatures published was increasing annually. The key word co-occurrence network showed that the research hotspots mainly focused on the study of epidemiology, risk factors, symptoms, and other aspects of WMSDs. The cooperation network and time network of counties and regions showed that America and Europe were at the leading position in the field of WMSD, and the top three were America, Canada and Sweden. The developing countries, like Brazil and China, had also begun to make relative research since 2000. In research cooperation, the collaboration among countries, research institutions was relatively close, and multiple leading core authors and teams were formed in the international arena. Conclusion The CiteSpace software can directly demonstrate the hotspots and tendency in the area of WMSDs.

OBJECTIVE: To analyze the prevalence and influencing factors of multisite work-related musculoskeletal disorders(WMSDs) of workers in a railway vehicle manufacturing enterprise. METHODS: A total of 366 male workers in the assembly and riveting workshop of a railway vehicle manufacturing enterprise were selected as the research subjects using the cluster sampling method. The Chinese Musculoskeletal Questionnaire was used to investigate the prevalence of multiple sites of WMSDs. Multiple logistic regression analysis was used to analyze the influencing factors. RESULTS: The total prevalence of WMSDs was 56.3%(206/366). The prevalence of WMSDs in all parts from high to low was as follows: lower back(35.5%), hand and wrist(27.6%), neck(23.2%), shoulder(21.0%), knee(19.9%), upper back(18.6%), hip and leg(18.0%), ankle/foot(15.8%) and elbow(12.3%)(P<0.01). The total prevalence of multisite WMSDs was 38.0%(139/366). The prevalence of WMSDs in different numbers of parts from high to low was as follows: 6 or more parts(12.0%), 2 parts(10.7%), 3 parts(6.6%), 5 parts(5.5%) and 4 parts(3.3%)(P<0.01). Multiple logistic regression analysis results showed that the overweight and obese workers had higher risk of multi site WMSDs than those with normal body mass index(P<0.05).Those with long-term low heads, frequent bending, long bending of the elbows, and higher frequency of work requirements, and less frequently communicated with the leader had higher risk of multi site WMSDs(P<0.05). CONCLUSION: The prevalence of multisite WMSDs in railway vehicle manufacturing enterprise is relatively high. The influencing factors include individual factors, adverse ergonomic factors and psychosocial factors.

OBJECTIVE: To explore the occurrence pattern of work-related musculoskeletal disorders( WMSDs) in electronic parts processing workers. METHODS: A total of 498 workers from an electronic parts processing factory were selected as study subjects by judgement sampling method. The prevalence of WMSDs in the past 1 year was investigated by using the China Musculoskeletal Questionnaire. The potential category model was used to classify the categories of WMSDs. RESULTS: The incidence of WMSDs in the past 1 year was 46. 8%( 233/498). Among them,the incidence of WMSDs involving only one site was 13. 1%( 65/498),and those involving at least 2 sites were 33. 7%( 168/498). The multi-site WMSDs were about 6-58 times of the single-site WMSDs. According to potential category analysis,the occurrence patterns of WMSDs were divided into three categories: i) cervical and shoulder occurrence group( 135 persons,27. 1%); ii) all parts group( 31 persons,6. 2%); iii) few or no site group( 332 persons,66. 7%). CONCLUSION: The occurrence of multi-site WMSDs in electronic parts processing workers were more common than the single-site. Analysis of potential category can be used to explore the occurrence pattern of WMSDs.

Aim To investigate the effect of salvianolate syophilized injection on brain tissue gene expression profiles in stroke of diabetic rats.Methods T1DM was induced in adult male Wistar rats by injecting streptozotocin.T1DM rats were then subjected to 90 minutes of middle cerebral artery occlusion(MCAO).The rats were randomly assigned to sham group(DM+Sham),ischemia-reperfusion group(DM+ MCAO/R),edaravone group(6 mg·kg-1,ED)and salvianolate lyophilized injection treatment group(5.25,10.5,21 mg·kg-1,SLI)with 13 rats in each group.Drugs were administered by tail vein injection 3 hours after MCAO/R,daily and lasting for 14 days.Infarct volume and gene expression in the brain tissue were detected by TTC staining and the gene chip technique.Results Compared with DM+Sham group,67 differential expressed genes were detected in the DM+MCAO/R group,among which 41 genes were up-regulated and 26 genes were down-regulated.Compared with DM+MCAO/R group,59 differential expressed genes were detected in the SLI(21 mg·kg-1)group,among which 45 genes were up-regulated and 14 genes were down-regulated.Hierarchical cluster results suggested that a number of genes were significantly changed in T1DM rats,such as Ly6i,Pax7 and Irx2.Effects of SLI on the stroke in T1DM rats were majorly related to coagulation and hemostasis system,inflammatory cytokines,oxidative stress,substance metabolism,angiogenesis and signal transduction.Conclusion Salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in type 1 diabetic rats through regulation of the coagulation and hemostasis system,inflammatory cytokines,oxidative stress,substance metabolism,angiogenesis and signal transduction.

There are some shortcomings of animal experiments applied in chemical toxicity testing, such as long period, large cost, species differences and dose differences, which limit the use of animal experiments' results in predicting human toxicity.Accordingly, we established a toxicity testing alternative screening system in line with the toxicity endpoints which required in chemical safety evaluation and risk assessment (genotoxicity, carcinogenicity, reproductive toxicity, acute toxicity and general toxicity) based on 3R principles (replacement, reduction, refinement) for animal experiments.This system covers most of the endpoints of toxicity assessment, and molecular biology technology was also applied to integrate the toxicity test, as well as some operation was optimized in order to shorten the experimental period, reduce experimental costs, improve animal welfare.Furthermore, the results from the screening system have higher clinical relevance because it is based on the toxicity mechanisms.