G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Tumor has become the major reasons cause of death,and its vaccine has become the effective tracts of treatment and prevention by enhancing the immune response of patients.However,most vaccines which are recombination subunit protein antigens are poorly immunogenic and difficult to induce a robust immune response in patients with compromised immune systems,resulting in poor marketing approval.The core component of the vaccine adjuvant can greatly enhance the strength,speed and duration of the immune response,thus becoming the key to the development of an ideal tumor vaccine.Most tumor vaccines are combined with tradition adjuvant such as aluminum,MF59 and AS adjuvant,but their products and patents are monopolized by large foreign companies.We found that natural adjuvants have many unique advantages,such as good biocompatibility and biodegradability,promoting the maturation of dendritic cell and the secretion of immune cytokines,significantly enhancing the tumor vaccine immune response,etc.In this paper,the application and future development of natural polysaccharides,saponins,flavonoid and plant virus-like particles in cancer vaccines were reviewed,which may lay a solid foundation for the development of the original and innovative adjuvants with domestic independent intellectual property rights.

Objective - To analyze the prevalence and influencing factors of work related musculoskeletal disorders (WMSDs) Methods among painters in the manufacturing industry. A total of 639 painters from one shipbuilding enterprise, one automobile manufacturing enterprise and three wooden furniture manufacturing enterprises in Guangdong Province were selected as the research subjects using typical sampling method. The Chinese version of Musculoskeletal Disorders Questionnaire was Results used to investigate the prevalence of WMSDs in the past one year, and the influencing factors were analyzed. The total prevalence rate of WMSDs among painters in the manufacturing industry was 37.4%. The prevalence of WMSDs in different vs vs P industries from high to low was shipbuilding, automobile and furniture manufacturing (50.0% 38.7% 29.0%, <0.01). The prevalence of WMSDs in different parts of the body from high to low was neck, ankle/foot, shoulder, low back, upper back, knee, vs vs vs vs vs vs vs vs P hand/wrist, hip/leg and elbow (20.7% 19.2% 17.4% 15.8% 14.1% 13.8% 13.5% 9.5% 6.6%, <0.01). Multivariate logistic regression analysis results showed that working in uncomfortable postures was a risk factor for neck, ankle/ P P foot and shoulder WMSDs (all <0.01); long time head turning was a risk factor for neck and shoulder WMSDs (both <0.05); P overweight and obesity, and bending and turning frequently at the same time were risk factors for ankle/foot WMSDs (all <0.05); P adequate rest time was a protective factor for neck and ankle/foot WMSDs (both <0.01); participated in physical exercise more P than once a week was a protective factor of neck and shoulder WMSDs in painters (all <0.05), after excluding the influence of Conclusion confounding factors. The prevalence of WMSDs in manufacturing painters was high, and the main body parts E mail 4813545@qq.com E mail wangzhongxu2003@163.com· · 中国职业医学 年 月第 卷第 期 ， ， ， 482 2022 10 49 5 Chin Occup Med October 2022 Vol.49 No.5 involved were neck, ankle/foot and shoulder. The influencing factors include individual factors, poor ergonomics factors and unreasonable work organization.

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.
Animals ; Dust ; Lung ; Male ; Pulmonary Fibrosis/metabolism* ; Rats ; Silicon Dioxide/adverse effects* ; Silicosis/metabolism* ; Transforming Growth Factor beta1/metabolism*

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg^-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg^-1) on day 36 or a dose of 40 mg kg^-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg^-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg^-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
Adult Germline Stem Cells/transplantation* ; Animals ; Azoospermia/chemically induced* ; Busulfan/toxicity* ; Disease Models, Animal ; Infertility, Male/chemically induced* ; Injections, Intraperitoneal ; Male ; Mice ; Spermatogenesis/drug effects* ; Spermatogonia/drug effects* ; Stem Cell Transplantation/methods*