Objective:To investigate the interventional and protective effect of low-dose L-carnitine(LC)against reproductive system damage in male Wistar rats during acute exposure to simulated high-altitude environment.Methods:A total of 24 specific pathogen-free male Wistar rats,aged 12 weeks,were randomly divided into control group,high-altitude model group,and LC intervention group[intraperitoneal injection of LC at a dose of 50 mg/(kg·d)],with 8 rats in each group.The rats in the control group were fed under normal conditions(at an altitude of approximately 1 500 m),those in the high-altitude model group,and those in the LC intervention group were fed in a hypobaric oxygen chamber(at a simulated alti-tude of 6 000 m).The rats were sacrificed after 3 days.The testis was collected to calculate testicular index;the semen was collected from the epididymis,and the Weili sperm quality analysis system was used to assess sperm quality;blood samples were collected from the abdominal aorta,and ELISA kits were used to measure the serum levels of testosterone(T),luteinizing hormone(LH),and follicle-stimulating hormone(FSH);testicular tissue samples were collected,and biochemical kits were used to measure the activity of reactive oxygen species(ROS),malondialdehyde(MDA),and superoxide dismutase(SOD);testicular tissue was collected to prepare HE and electron microscopy sections,and a light microscope and a transmission electron microscope were used for observation.Results:Com-pared with the blank control group,the high-altitude model group had significant increases in the levels of T,LH,and FSH(P<0.01),testicular tissue damage under the light microscope,and changes in the morphology of spermatogenic cells,including mitochondrial al-terations,membrane edema,loss of cristae,swelling of the matrix,and local dissolution,as well as significant increases in the levels of ROS and MDA(P<0.01)and a significant reduction in SOD activity(P<0.01).Compared with the high-altitude model group,the LC intervention group had a significant increase in the level of T(P<0.01),significant reductions in the levels of FSH and LH(P<0.01),and significant improvements in the pathological changes of testicular tissue,with no marked mitochondrial injury,and there were sig-nificant reductions in the levels of ROS and MDA(P<0.01)and a significant increase in SOD activity(P<0.01).There was no signifi-cant difference in testicular index between groups(P>0.05).The high-altitude model group had a significantly lower sperm count than the blank control group(P<0.05),while there was no significant difference in sperm count between the LC intervention group and the blank control group(P>0.05);there was no significant difference in sperm motility between groups(P>0.05).Conclusion:Low-dose LC can improve reproductive system damage in rats during acute exposure to simulated high-altitude environment,possibly by alleviat-ing oxidative stress response.

Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.

Objective: To investigate the effects of plateau environment exposure on the reproductive system of male rats, so as to provide the reference for mechanisms of reproductive damage in plateau environment. Methods: Sixty SPF-grade 12-week-old male Wistar rats were randomly divided into the plain-exposed group, the 1 day-, 3 day-, 7 day-, 14 day- and 28 day- plateau-exposed groups. The rats in the plain-exposed group were raised under normal conditions for 28 days, while the rats in the plateau-exposed groups were raised in a simulated high-altitude plateau chamber. After the completion of the designated feeding periods, the rats were sacrificed under anesthesia, and testicular tissue and abdominal aortic blood were collected to detect the testicular index and evaluate sperm quality. Histological and cellular morphologies of the testicular tissue were analyzed. Additionally, the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) in the testicular tissue were determined, along with serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Conclusions Plateau environment may cause a decrease in testicular index and sperm quality, impair mitochondrial function, induce oxidative stress, and thus affect reproductive system of male rats. However, there are signs of self-repair in the reproductive system with the increase of exposure duration.

Objective To investigate the prevalence and changing trend of Enterobius vermicularis infections among children in Shandong Province, so as to provide the scientific evidence for the adjustment and development of the enterobiasis control strategy. Methods Soil-borne nematodiasis surveillance sites were assigned in 51 counties (districts, cities) in Shandong Province from 2016 to 2020, and the E. vermicularis infections were detected using a modified Kato-Katz technique and the cellophane tape method among children at ages of 3 to 9 years living in these surveillance sites. The epidemiological profiles of E. vermicularis-infected children were descriptively analyzed. Results A total of 5 060 children at ages of 3 to 9 years were detected in 51 soil-borne nematodiasis surveillance sites in Shandong Province from 2016 to 2020, and the overall prevalence of E. vermicularis infections was 2.23%. The annual prevalence of E. vermicularis infections was 3.99% (26/651), 1.70% (14/824), 0.96% (8/837), 2.90% (45/1 552) and 1.67% (20/1 196) from 2016 to 2020, respectively, with a significant difference detected among years ( χ² = 21.455, P < 0.01). The prevalence of E. vermicularis infections was 1.25% (15/1 198), 1.85% (14/755), 3.18% (84/2 640) and 0 (0/467) among children from central, eastern, southern and northern Shandong Province (χ² = 27.326, P < 0.01). In addition, there was no significant difference in the prevalence of E. vermicularis infections between male (1.98%, 56/2 831) and female children (2.56%, 57/2 229) (χ² = 1.916, P > 0.05); however, there was age-specific prevalence of E. vermicularis infections among children (χ² = 16.448, P < 0.05), with the greatest prevalence detected among children at ages of 6 years (3.18%, 25/786), and the lowest prevalence seen among children at ages of 3 years (0.75%, 6/800). Conclusions The prevalence of E. vermicularis infections remained at a medium level among children at ages of 3 to 9 years in Shandong Province from 2016 to 2020, with region-specific prevalence found across the province. An integrated strategy is required for enterobiasis control.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

Objective: To investigate the protective effect of compound Longmaining isoprenaline hydrochloride-induced myocardial infarction model and its effect on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-kappa B (NF-κB) signaling pathway.Method: Forty-eight male SD rats were randomly divided into 6 groups:normal group,model group,compound salvia miltiorrhiza drop pill group (0.072 9 g·kg^-1),and low,medium and high-dose compound Longmaining decoction groups (0.36,0.71,1.43 g·kg^-1).The acute myocardial infarction model was induced through subcutaneous injection with isoproterenol.The pathological changes of myocardial tissue were examined by hematoxylin-eosin (HE) staining.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemotaxis protein-1(MCP-1) and nitrogen (NO) in serum were measured by enzyme linked immunosorbent assay (ELISA).The expression levels of inhibitors of NF-κB kinase subunit-β(IKKβ),NF-κB inhibitor α(IκBα),TLR4,MyD88 and NF-κB p65 were measured by immunohistochemical staining and Western blot.Result: Compared with normal group,the myocardial injury in model group was obvious.The levels of IL-1β,IL-6,TNF-α,MCP-1 and NO in serum increased significantly (P<0.05),the expression level of IκBα decreased significantly (P<0.05),and the expression levels of IKKβ,TLR4,MyD88 and NF-κB p65 increased significantly in myocardial tissue (P<0.05).Compared with model group,low,medium and high-dose compound Longmaining groups could significantly alleviate the degree of myocardial injury in rats,significantly decrease IL-1β,IL-6,TNF-α,MCP-1 and NO levels in the serum (P<0.05),significantly increase the expression level of IκBα(P<0.05),and decreased the expression levels of IKKβ,TLR4,MyD88 and NF-κB p65(P<0.05).Conclusion: Compound Longmaining plays a protective effect on acute myocardial infarction by regulatingthe expressions of TLR4/MyD88/NF-κB p65 signaling pathway and relevant inflammatory factors.

Danhong injection (DHI) and ceftriaxone sodium were used in combination based on their experimental uses in clinic. This study was designed to investigate the impact of ceftriaxone on pharmacokinetics and pharmacodynamics of the phenolic acids from DHI. After administration of DHI for 7 d, ceftriaxone (CFTX) was combined with DHI for the next 7 d in adult male Sprague-Dawley (SD) rats. All the drugs were administered through caudal vein. UHPLC-TQ-MS was applied in determining the plasma concentration of p-coumaric acid (p-CA), salvianolic acid D (SaD), rosmarinic acid (RA) and salvianolic acid B (SaB). The pharmacokinetic parameters of the combination group or the Danhong injection alone group were calculated by statistical moment method, C_max and the average of the area under the curve AUC_0-t using 90% confidence interval of the bioequivalence and bioavailability degree module in DAS 3.2.8 statistic software. The results showed that C_max of p-CA, SaD, RA and SaB were unqualified within 90% confidence intervals for bioequivalence statistics. And the results showed that AUC_0-t of SaD, RA and SaB within 90% confidence intervals for bioequivalence statistics were unqualified. There were no significant difference in the t_max (P>0.05). The results of anticoagulation in vivo showed that the international normalized ratio (INR), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) were significantly increased when combined with CFTX (P<0.05 or P<0.01). The results in antithrombotic effects revealed that the thromboxane B₂ (TXB₂) level in serum was significantly decreased (P<0.01) in the combination group compared with Danhong injection alone. However, there was no significant difference in antiplatelet effects. These results suggest that CFTX may enhance the anticoagulation and antithrombotic effects of DHI through altering pharmacokinetics and pharmacodynamics in SD rats.

Objective To investigate the mechanism of tetramethylpyrazine combined with cisplatin on the transplanted tumor growth and angiogenesis inhibition of Lewis lung adenocarcinoma in mice.Methods Lewis lung carcinoma model of C57BL/6 mice were produced by under arm injection of Lewis lung cancer cells.Then the tumor-bearing mice were randomized into fore groups,with 15 mouse in each group:model group,cisplatin group,tetramethylpyrazine (TMP) group and combined group(TMP + cisplatin).Control group was given with 0.9％ NaCL 0.2 mL,cisplatin group was given with 2 mg· kg-1 cisplatin 0.2 mL,TMP group was given with 100 mg · kg-1 TMP 0.2 mL,combination group was TMP + cisptatin groups,per 0.2 mL.All mouse were sacrificed after intraperitoneal injection for two weeks.Subcutaneous tumors were processed for tumor weight,and the tumor inhibitory rate was calculated.The expressions of vascular endothelial growth factor (VEGF)and Vasohibin-1 (VASH-1) were determined by immunohistochemistry.Results Compared with model group (tumor inhibition rate:0),tumor inhibition rate in combination group,cisplatin group,TMP group were 54.81％,32.36％,18.36％ with statistically significant difference between groups (all P ＜ 0.05).The expression levels of VEGF in combination group,cisplatin group,TMP group,model group were 20.37 ± 2.02,28.07 ± 4.29,26.43 ± 4.69,62.14 ±6.78,respectively.The expression levels of VASH-1 in the four groups were 9.04 ± 1.01,10.10± 1.61,11.53 ± 1.96,12.94 ± 1.10,with statistically significant difference between groups (all P ＜ 0.05).Pearson correlation analysis:the VEGF and VASH-1 was positively correlated (r =0.664,P ＜ 0.05).Conclusion Tetramethylpyrazine has synergetic inhibitory effect with cisplatin on transplanted tumor growth of Lewis lung carcinoma in mice.The action mechanism may be due to exert direct effects on cancer cell and down-regulate the VEGF and VASH-1 expression,inhibiting tumor angiogenesis.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

Naoxintong capsule has beneficial effects for activating blood circulation, dispersing blood stasis and dredging collateral. It is widely used in the treatment of coronary heart disease, angina pectoris, stroke and cardiovascular disease. However, the pharmacodynamic basis and possible mechanism of its preventive effects are not clear. In this study, 10 male and 10 female C57BL/6 mice were used, and were randomly divided into the control group (saline) and Naoxintong group. Adaptively fed for 7 days in common conditions, mice were given Naoxintong capsule or saline for 3 days via intragastric administration. Serum was collected from 6 mice in each group 1 h after the last administration. Serum proteins were prepared to do two-dimensional gel electrophoresis. Then image analysis and mass spectrometry detection were carried out to screen and identify the differentially expressed proteins and make bioinformatics analysis. It was found that 24 differentially expressed proteins between Naoxintong group and control group. Compared with the control group, 12 proteins were increased, and 12 were decreased. The proteins were involved in apoptosis signal pathway and vascular endothelial growth factor signal transduction pathway, in which vasohibin-1 is a negative feedback regulation factor in angiogenesis. Western blot showed that the expression of vasohibin-1 in Naoxintong group was reduced, which is consistent with the result in two-dimensional electrophoresis. Serum proteins expression is different between Naoxintong and control groups. The targets of these differentially expressed proteins include endothelial cells, inflammatory cells and platelets. The changes on proteins showed that Naoxintong capsule may ameliorate coronary heart disease and ischemic cerebrovascular disease, and provide potential biological markers to prevent ischemic disease.