Objective： Varicocele (VC) induces male infertility by mediating changes in the testicular microenvironment, in which testicular hypoxia and high-pressure are important pathological conditions. This study aims to compare the mouse spermatogenesis (GC-2spd) cells and Sertoli (TM4) cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling, and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model. Methods： On the basis of cell hypoxia induced by CoCl2, the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution. After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model, the cells were divided into normal group, hypoxia model group and composite model group. And the levels of OS, programmed cell death, inflammatory factors, and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods. Results： The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L, respectively, and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg (P<0.05). Compared with the normal group, the SOD levels of GC-2 and TM4 cells decreased (all P<0.05), CAT level decreased (all P<0.05), and MDA level increased (all P<0.01), and the OS level of GC-2 and TM4 cells was more obvious than that of the hypoxia model group (all P<0.05). Compared with the normal group, apoptosis occurred in GC-2 and TM4 cells after composite modeling (all P<0.05). Compared with the normal group, the mRNA expressions of IL-1β, IL-18, TNF-α and COX-2 in GC-2 and TM4 cells significantly increased (P<0.01) and higher than those in hypoxia model group (P<0.05) and induced pyroptosis (P<0.01). The expression level of GSDMD increased (P<0.05). Conclusion： The cell model with hypoxia and high pressure combined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone, but also further cause inflammatory response damage and pyroptosis, which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC. This cell model can be used for studying the pathogenesis of VC-associated male infertility, evaluating drug efficacy, and exploring pharmacological mechanisms.
Male ; Animals ; Varicocele/pathology* ; Mice ; Testis/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Hypoxia ; Cobalt ; Sertoli Cells/metabolism* ; Osmotic Pressure ; Spermatogenesis ; Cellular Microenvironment ; Infertility, Male ; Disease Models, Animal

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).

【Objective】 To investigate the role of transnasal ileus tube combined with somatostatin in the treatment of early postoperative inflammatory small bowel obstruction(EPISBO) in elderly patients with gastrointestinal tumor. 【Methods】 A total of 107 elderly patients with EPISBO after gastrointestinal tumor surgery were enrolled into this retrospective study. According to adopted treatment plan, they were divided into two groups: the observation group treated with transnasal ileus tube combined with somatostatin and the control group treated with nasogastric tube combined with somatostatin. Then we compared the therapeutic efficacy and adverse reactions between the two groups. 【Results】 The response rate was 98.21% in the observation group, significantly higher than 86.27% in the control group(χ²=3.910, P<0.05). Compared with those in the control group, in the observation group, we found significantly larger amounts of abdominal circumference reduction and gastrointestinal decompression in the first 48 h(P<0.05); significantly earlier stoppage of vomiting, first passage of flatus, self-defecation, disappearance of air fluid level and significantly shorter post-obstruction duration of hospitalization(P<0.05). After 8-day treatment, the inflammatory indicators was significantly decreased(P<0.05). No significant difference was found in incidence of adverse reactions between the two group(χ²= 1.874, P>0.05) . 【Conclusions】 The transnasal ileus tube combined with somatostatinis effective and safe in the treatment of EPISBO in elderly patients with gastrointestinal tumor, so it is worth popularizing in clinic.

OBJECTIVE: To observe the effects on hippocampal neuronal structure and hippocampal monoamine neurotransmitters such as norepinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) with acupuncture for promoting the circulation of the governor vessel and regulating the mental state ( acupuncture) in rats with post-stroke depression and explore the underlying effect mechanism of acupuncture on post-stroke depression. METHODS: A total of 48 clean-grade SD rats were randomized into a sham-operation group, a model group, a Tongdu Tiaoshen acupuncture group and a non-meridian-non-acupoint group, 12 rats in each one. In the model group, the Tongdu Tiaoshen acupuncture group and the non-meridian-non-acupoint group, the compound method of cerebral medial arterial occlusion and the chronic unpredictable mild stress was adopted to prepare the model of post-stroke depression. In the sham-operation group, skin was opened and the fascia muscle was separated, after artery exposed, no ligation was operated and the incision was sutured directly. In the sham-operation group and the model group, no any intervention was performed. In the Tongdu Tiaoshen acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Shuigou" (GV 26), "Shenting" (CV 24) and "Dazhui" (GV 14) for 40 min in each treatment and the needles were manipulated at the acupoints once in 20 min. The treatment was given once a day, 6 times a week for 4 weeks consecutively. In the non-meridian-non-acupoint group, the depression between the 3rd and 4th metatarsal bones on the dorsum of the forelimb was selected in intervention and the needling technique was same as the Tongdu Tiaoshen acupuncture group. The behavioral changes were observed after intervention in each group. Using transmission electron microscopy, the ultrastructure of hippocampal CA 1 neurons was observed in the rats of each group. Using high performance liquid chromatography, the contents of NE, 5-HT and DA were determined. RESULTS: Compared with the sham-operation group, the Zea-longa neurobehavioral score was increased (<0.01), the sucrose water consumption was reduced (<0.01), the number of times of horizontal movement and vertical movement in open-field test were reduced (both <0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was aggravated and the contents of NE, 5-HT and DA were reduced in the model group (<0.01). Compared with the model group, the Zea-Longa neurobehavioral score was reduced (<0.01), the sucrose water consumption was increased (<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both <0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (<0.01, <0.05). Compared with the non-meridian-non-acupoint group, the Zea-Longa neurobehavioral score was reduced (<0.01), the sucrose water consumption was increased (<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both <0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (<0.01, <0.05). CONCLUSION The acupuncture improves the behavior of the model rats with post-stroke depression, repairs hippocampal neuronal damage, which is probably related to the contents of hippocampal monoamine neurotransmitters (NE, 5-HT and DA).
Acupuncture Therapy ; Animals ; Depression ; Hippocampus ; Neurons ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Stroke

Objective To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China, 2016. Methods Non-duplicated nosocomial cases as well as pathogens causing bloodstream infections ( BSI) , hospital-acquired pneumonia ( HAP) and intra-abdominal infections ( IAI ) from 12 teaching hospitals across China were collected. The minimum inhibitory concentrations (MICs) of important clinical common strains were determined by agar dilution method or broth microdilution method. The CLSI M100-S27 criteria was used for interpretation. Data were analyzed by using WHONET-5. 6 software. Results A total of 2060 cases were collected, including 894 cases from BSI, 630 cases from HAP and 536 cases from IAI. The MICs of 1896 important clinical common strains were determined. Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI, while Acinetobacter baumanii and Pseudomonas aeruginosa were dominated in HAP. All Staphylococcus aureus were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. Methicillin-resistant S. aureus accounted for 44. 4％ ( 75/169 ) of all the S. aureus. The rate of methicillin-resistant coagulase-negative staphylococci was 80. 9％ ( 72/89 ) . No Enterococcus strains were found resistant to tigecycline, linezolid or daptomycin. Vacomycin resistant enterococcus was found in Enterococcus faecium, accounting for 1. 8％ ( 2/111 ) of all E. faecium strains. Tigecycline, meropenem, amikacin, imipenem, and polymyxin B exhibited high potency against Enterobacteriaceae and the susceptibility rates were 96. 6％(865/895), 94. 3％ (859/911), 94. 2％ (858/911), 94. 1％ (857/911), and 91. 6％ (820/895), respectively. The prevalence of extended-spectrum β-lactamase was 58. 4％ ( 263/450 ) in E. coli and 28. 6％ ( 84/294 ) in K. pneumonia. The rate of carbapenem resistant K. pneumonia and E. coli was 15. 3％ ( 45/294 ) and 1. 8％ ( 8/450 ) , respectively. The percentage of polymyxin B resistant K. pneumonia and E. coli was 4. 1％ ( 12/294 ) and 4. 4％ ( 20/450 ) , respectively. The rate of tigecycline resistant K. pneumonia and E. coli was 2. 4％ ( 7/294 ) and 0. 2％ ( 1/450 ) , respectively. A. baumanii showed low susceptibility to the antimicrobial agents except tigecycline ( 91. 4％, 235/257 ) and polymyxin B (100％, 257/257). The rate of carbapenem resistant A. baumanii was 80. 5％ (207/257). The rate of carbapenem resistant P. aeruginosa was 31. 7％ ( 59/186 ) . Polymyxin B and amikacin demonstrated high antibacterial activity against P. aeruginosa with susceptility rate of 100％ ( 186/186 ) and 90. 9％ ( 169/186), respectively. Conclusions Nosocomial pathogens showed high susceptibilities against tigecycline and polymyxin B. Antimicrobial resistance in A. baumannii is a serious problem. The prevalence of carbapenem-resistant Enterobacteriaceae and polymyxin B resistant Enterobacteriaceae has increased, which should be monitored continuously in China.

Objective To investigate the pharmacokinetics of cyclosporine(CsA) in type 1 diabetes of rats.Methods Rats with type 1 diabetes were induced by intraperitoneal administration of 65 mg· kg-1 streptozotocin (STZ).Pharmacokinetics of CsA (10 mg· kg-1) was compared between diabetic and normal rats on the 5 weeks after STZ injection.Concentration of CsA in whole blood was measured by enzyme multiplied immunoassay technique.Results Type 1 diabetes rats were successfully induced as the fasting blood glucose levels exceeded 11.1 mmol · L-1 after STZ injection for 1 week.Beside glucose,total cholesterol (TC) and triacylglycerol (TG) in serum of diabetic rats were significantly higher than those in normal rats after STZ injection for 5 weeks.Unlike normal rats,the pharmacokinetics of CsA in diabetic rats exhibited a double peak after oral administration.The Tmax and Cmax were lower in diabetic rats than normal rats,although without statistical differences as follows:Tmaxwas (3.3±1.6),(3.2 ±2.5) h,Cmax was (579.0±208.5),(453.0 ± 104.8) ng· mL-1 in normal and diabetic rats.Compared with normal rats,AUC and t1/2 of CsA in diabetic rats decreased significantly,which were 0.51 and 0.70 times those of normal rats,respectively;AUC was (7343.2 ± 2333.7),(3729.7 ± 1106.6) h ·ng · mL-1,t1/2 was (8.5 ± 1.5),(6.0 ± 0.9) h in normal and diabetic rats.Conclusion The oral pharmacokinetics of CsA was significantly different in type 1 diabetic rat model compared to normal controls,which should be taken into consideration in clinical medication.

Objective To investigate the effect of glucose metabolism alteration induced by alloxan intraventricular injection on learning and memory abilities of mice, and its role in the development of AD. Methods Mice were randomly divided into high-dose alloxan intraventricular injection group (n=7, 4 mg/kg) and low-dose alloxan intraventricular injection group (n=7, 1.5 mg/kg)and control group (n=7, physiological saline); intraventricular injection of alloxan, the O-GLcNAc transferase inhibitor, was performed in the high-dose and low-dose alloxan intraventricular injection groups to interfere the brain glucose metabolism. Morris water maze was used to detect the learning and memory abilities of mice. Western blotting and immunohistochemistry were used to analyze the alterations of phosphorylation and O-Glycosylation of neurofilament in mice brain induced by alloxan intraventricular injection. Results In the located navigation tests, the swimming time and distance to find the platform in the mice of alloxan administration were significantly increased as compared with those in the control group (P＜ 0.05); in space exploration experiments, compared with those in the control mice, the number of crossing the hidden platform was decreased and the initial angle of entry to water was increased in the mice of alloxan administration (P＜0.05). Western blotting and immunohistochemistry displayed that phosphorylation was obviously increased and the O-Glycosylation was significantly reduced in the cytoskletal neurofilament of the mice with alloxan administration as compared with those in the control group (P＜0.05), which was similar to the alteration of neurofilament's modification in AD brain. Conclusion The inventricular injection of alloxan could impair the learning and memory of mice, which might have a relation with the dysregulation of phosphorylation and O-Glycosylation in neurofilament caused by the impaired glucose metabolism, which is similar to the alteration of phosphorylation and O-Glycosylation in neurofilament in AD brain.

OBJECTIVETo investigate the effect of lamivudine, interferon alpha and oxymatrine treatment for surviving hepatic failure patients with hepatitis B.

METHODS200 hepatitis B patients, including 100 subacute or acute-on-chronic hepatic failure survivals (group A), and 100 chronic (group B, n=100) hepatic failure survivals, were enrolled in this study. Patients in group A received interferon alpha (n=35), lamivudine (n=33) , or combinational lamivudine and oxymatrine (n=32) therapy for six months; Patients in group B received lamivudine (n=49), or combinational lamivudine and oxymatrine (n=51) therapy for six months, respectively. After the treatment, all patients were followed-up for six months.

RESULTSAt the end of follow-up, all patients in group A survived, while in group B three patients (6.1%) receiving lamivudine, and four (7.8%, P>0.05) receiving combinational therapy died; more than 90% of all survivals had their HBV DNA loss. The HBeAg/anti-HBe seroconversion rate in patients of group A treated with interferon alpha (9/17, 52.9%) was higher than that in patients treated with combinational lamivudine and matrine (5/16, 31.3%, P<0.05), which was higher than that in the patients treated with lamivudine alone (1/17, 5.9%, P<0.01), and the Knodell histological activity index score in patients treated with lamivudine (7.2+/-0.8, P<0.05) was lower than that in patients treated with interferon alpha (8.2+/-1.3, P<0.05), and the best efficacy was found in receiving combinational therapy (6.9+/-0.7, P<0.01); Lamivudine or lamivudine in combination with matrine significantly inhibited the intrahepatic inflammatory activities, but had no effect on the existing fibrosis in group B patients.

CONCLUSIONLong term nucleotide analogues treatment may delay the progress of fibrosis in hepatitis B-induced hepatic failure survivals, and the administration of matrine in time may further enhance the anti-fibrotic effect of nucleotide analogues.

Adolescent ; Adult ; Alkaloids ; administration & dosage ; therapeutic use ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Hepatitis B ; complications ; drug therapy ; pathology ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; administration & dosage ; therapeutic use ; Liver Failure ; blood ; drug therapy ; pathology ; Liver Function Tests ; Male ; Middle Aged ; Quinolizines ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult