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

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To observe the adverse reactions of different anesthesia methods used in bronchoscopic diagnosis and treatment,and provide ideas for clinical selection of the best anesthesia methods.Methods 150 patients from June 2022 to June 2023 for bronchoscope were randomly divided into group W(atomization with lidocaine combined with intravenous sedation),group Q(laryngeal mask general anesthesia)and group H(lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia),with 50 cases in each group.Heart rate(HR),mean arterial pressure(MAP)and percutaneous arterial oxygen saturation(SpO2)values were recorded at different time points,adverse reactions during recovery,recovery time and dosage of anesthetic drugs were recorded.Results At T1 and T2,SpO2 in group W(89.4±0.7)%and(91.8±0.3)%were lower than that(99.6±0.8)%in T0,and lower than those(98.6±1.3)%and(98.5±1.6)%in group Q and(99.7±0.3)%and(98.4±1.6)%in group H,the difference were statistically significant(P<0.05).At T1 and T2,the MAP of group W were(108.5±7.8)and(105.6±7.3)mmHg,which were significantly higher than those of T0(87.5±8.6)mmHg,and higher than those of group Q(92.6±8.5)and(85.8±11.3)mmHg,respectively,higher than those(85.7±9.2)and(85.2±10.8)mmHg in group H,the differences were statistically significant(P<0.05).The MAP of group Q at T1 and T3 was(92.6±8.5)and(91.4±8.6)mmHg,respectively,higher than that of T0(87.8±7.5)mmHg,and higher than those of group H(85.7±9.2)and(86.5±7.2)mmHg,with statistical significance(P<0.05).At T1 and T2,the HR of group W was(92.7±9.6)and(91.3±9.2)times/min,higher than that of T0(72.3±8.4)times/min,and higher than those of group Q(75.3±11.6)and(78.5±12.8)times/min,respectively,and higher than those of group H(76.6±10.7)and(77.2±8.5)times/min,and the differences were statistically significant(P<0.05).The hypoxemia,arrhythmia and cough rates in group Q were higher than those in group W and group H,and the differences were statistically significant(P<0.05).The recovery time of group H was(11.5±7.2)min,which was significantly lower than that of group W(16.8±8.5)min and group Q(17.6±6.4)min,and the differences were statistically significant(P<0.05).The dosage of propofol in group H was(314.3±12.7)mg and remifentanil was(211.6±12.5)μg,both lower than those in group W(390.5±12.4)mg and(268.4±13.6)μg,and lower than those in group Q(387.6±15.2)mg and(372.5±15.3)μg.The differences were statistically significant(P<0.05).The dosage of micuronium chloride was(23.7±3.8)mg in group H,lower than(32.5±4.3)mg in group Q,and the difference was statistically significant(P<0.05).Conclusion Lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia is the best anesthesia method for bronchoscopic diagnosis and treatment,which is beneficial to respiratory management and less adverse reactions in perioperative period.

Objective: To investigate the association between physical exercise and non-alcoholic fatty liver disease (NAFLD) in people infected with HBV. Methods: The information about the 3 813 participants infected with HBV, including the prevalence of NAFLD, prevalence of physical exercise and other covariates, were collected from the National Science and Technology Major Project of China during 2016-2020. The logistic regression model was used to evaluate the association between physical exercise and NAFLD in HBV infected patients, and subgroup analysis was performed to identify the effect modifiers. Results: A total of 2 259 HBV infected participants were included in the final analysis and 454 (20.10%) had NAFLD. After adjusting for covariates, we found that moderate physical exercise was a protective factor for NAFLD (OR=0.66, 95%CI: 0.46-0.94). Subgroup analysis suggested that the protective effect of moderate physical exercise on NAFLD might be stronger in women (OR=0.61, 95%CI: 0.36-1.01), those <45 years old (OR=0.24, 95%CI: 0.06-0.80), those who had low education level (OR=0.16, 95%CI: 0.04-0.49), those who had low annual income (OR=0.39, 95%CI: 0.16-0.89 for <30 000 yuan RMB; OR=0.64, 95%CI: 0.40-1.00 for 30 000-80 000 yuan RMB), those who had hypertension (OR=0.45, 95%CI: 0.21-0.88), those with BMI ≥24.0 kg/m² (OR=0.66, 95%CI: 0.43-1.01), those who had more daily fruit or vegetable intake (OR=0.61, 95%CI: 0.38-0.97), those who had more daily meat intake (OR=0.49, 95%CI: 0.23-0.97), and those who had no smoking history (OR=0.66, 95%CI: 0.45-0.95) or passive smoking exposure (OR=0.61, 95%CI: 0.37-0.97). Conclusions: Among HBV infected patients, moderate physical exercise was negatively associated with the prevalence of NAFLD. Women, young people, those who had low education level, those who had low annual income, those with hypertension, those with high BMI, those who had more daily fruit or vegetable and meat intakes, and those who had no smoking history or passive smoking exposure might be more sensitive to the protective effect.
Humans ; Female ; Adolescent ; Middle Aged ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Hepatitis B virus ; Risk Factors ; Tobacco Smoke Pollution ; Exercise ; Hypertension

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD. METHODS: A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats. RESULTS: In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group. CONCLUSIONS Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.
Rats ; Male ; Animals ; Electroacupuncture ; Dyspepsia/therapy* ; Rats, Sprague-Dawley ; Ghrelin ; Gastrointestinal Hormones ; Serotonin ; Vasoactive Intestinal Peptide ; Acupuncture Points

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ² test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q₁, Q₃), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.
Humans ; Hyperaldosteronism/diagnosis* ; Nomograms ; Hypertension ; Cross-Sectional Studies ; Aldosterone ; Saline Solution ; Renin ; Potassium

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.
Aged ; Male ; Humans ; Aged, 80 and over ; Female ; Heart Failure/pathology* ; Retrospective Studies ; Stroke Volume ; Case-Control Studies ; Nucleic Acids ; 8-Hydroxy-2'-Deoxyguanosine ; Myocytes, Cardiac/pathology* ; RNA ; Oxidative Stress ; Guanine ; Ventricular Function, Left