This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration ( n = 36), sperm morphology ( n = 26), and sperm motility ( n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% ( n = 48), 25.6% ( n = 23), and 21.1% ( n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.
Humans ; Male ; Antioxidants/therapeutic use* ; Infertility, Male/therapy* ; Meta-Analysis as Topic ; Sperm Count ; Sperm Motility ; Systematic Reviews as Topic

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.
Male ; Rats ; Animals ; Reserpine ; Dopamine ; Rats, Wistar ; Hypotension/chemically induced* ; Norepinephrine

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult ; Humans ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Hypertension/epidemiology* ; Nomograms ; Ethnicity

Objective To measure the prevalence of mental health symptoms and identify the associated factors among college students at the beginning of coronavirus disease 2019(COVID-19)outbreak in China. Methods We carried out a multi-center cross-sectional study via snowball sampling and convenience sampling of the college students in different areas of China.The rates of self-reported depression,anxiety,and stress and post-traumatic stress disorder(PTSD)were assessed via the 21-item Depression-Anxiety-Stress Scale(DASS-21)and the 6-item Impact of Event Scale-Revised(IES-6),respectively.Covariates included sociodemographic characteristics,health-related data,and information of the social environment.Data pertaining to mental health service seeking were also collected.Multivariate Logistic regression analyses were performed to identify the risk factors. Results A total of 3641 valid questionnaires were collected from college students.At the beginning of the COVID-19 outbreak,535(14.69%)students had negative emotions,among which 402(11.04%),381(10.49%),and 171(4.90%)students had the symptoms of depression,anxiety,and stress,respectively.Meanwhile,1245(34.19%)college students had PTSD.Among the risk factors identified,male gender was associated with a lower likelihood of reporting depression symptoms(AOR=0.755,P=0.037],and medical students were at higher risk of depression and stress symptoms than liberal arts students(AOR=1.497,P=0.003;AOR=1.494,P=0.045).Family support was associated with lower risks of negative emotions and PTSD in college students(AOR=0.918,P<0.001;AOR=0.913,P<0.001;AOR=0.899,P<0.001;AOR=0.971,P=0.021). Conclusions College students were more sensitive to public health emergencies,and the incidence of negative emotions and PTSD was significantly higher than that before the outbreak of COVID-19.More attention should be paid to female college students who were more likely to develop negative emotions.We should strengthen positive and proper propaganda via mass media and help college students understand the situation and impact of COVID-19.Furthermore,we should enhance family support for college students.The government and relevant agencies need to provide appropriate mental health services to the students under similar circumstances to avoid the deterioration of their mental well-being.
COVID-19/epidemiology* ; Cross-Sectional Studies ; Female ; Health Status ; Humans ; Male ; Students/psychology* ; Universities

OBJECTIVE: To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of the clinical severity of ulcerative colitis (UC). METHODS: We retrospectively analyzed the clinical and endoscopic data of 167 patients diagnosed with UC in Beijing Tsinghua Changgung Hospital from January, 2015 to November, 2021. The severity of endoscopic lesions was determined by Mayo Endoscopic Score (MES, 0-3 points) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score (0-8 points), and the scope of endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification. RESULTS: The IMSE showed stronger correlations with modified Truelove and Witts Disease Severity, Mayo score and partial Mayo score (r=0.712, 0.784, and 0.703, respectively) than MES (r=0.642, 0.754, and 0.604, respectively), Montreal classification (r=0.598, 0.628, and 0.603, respectively) and UCEIS (r= 0.670, 0.767, and 0.677, respectively). ROC curve analysis showed that IMES was superior to MES, Montreal and UCEIS in diagnosis of severe and moderate- to-severe UC. IMES also showed stronger correlations with the laboratory indicators including CRP (r=0.583), WBC (r=0.235), HB (r=-0.280), PLT (r=0.352), ALB (r=-0.396) and ESR (r=0.471) than MES and Montreal classification. An IMES score of 5 was of greater value than a MES score of 3, E3, and UCEIS≥6 for predicting the administration of systemic hormones, immunosuppressants, or surgery in the near future. CONCLUSION IMES can better reflect the clinical severity of UC and has good correlations with the laboratory indicators of the patients.
Colitis, Ulcerative/diagnosis* ; Colonoscopy ; Humans ; ROC Curve ; Retrospective Studies ; Severity of Illness Index

Objective: To explore the efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Seventy-three patients(including 60 males and 13 females) with OSAHS admitted to the department of otorhinolaryngology of our hospital in recent two years were retrospectively analyzed. All the patients had velopharyngeal obstructionevaluated by electronic endoscopic Müller test and were divided into control group (34 cases) and observation group (39 cases). The patients in the control group were performed modified uvulopalatopharyngoplasty, while those in the observation group were performed relocation and expansion pharyngoplasty by suspension sutures.The scores of ESS, AHI and LSaO₂ before and after treatment were collected and compared. Results: The total effective rate of the observation group was 94.87%, which was significantly higher than 79.41% of the control group. The AHI was lower and LSaO₂ value was higher (χ²=-1. 896,-1. 968,P<0.05)in the observation group. The sleeping symptoms and quality of life of the two groups were significantly improved. The ESS score of the observation group was decreased more significantly than that of the control group after treatment, and the difference was statistically significant (χ²=-1.451,P<0.05). The incidence of foreign body sensation in pharynx of the observation group (89.74%) was higher than that of the control group (55.88%), and the postoperative bleeding and postoperative recurrence rate (0.00%, 2.56%) was lower than that of the control group (8.82%, 14.70%)with statistical significance (χ²=4.738,4.249,4.119,P<0.05).The incidence of transient nasopharyngeal reflux in both groups was low and statistically insignificant (χ²=0.629,P>0.05). Conclusions: Preoperative strict screening of indications plays an important role in the selection of palatopharyngeal surgery methods and curative effect. Relocation and expansion pharyngoplasty by suspension sutures can improve the clinical efficacy of OSAHS with better safety and less recurrence.
Female ; Humans ; Male ; Palate, Soft/surgery* ; Pharynx/surgery* ; Quality of Life ; Retrospective Studies ; Sleep Apnea, Obstructive/surgery* ; Sutures

Objective:To systematically investigate the chemical constituents of 90% ethanol extract of Corydalis impatiens，and evaluate their inhibitory effect on cell proliferation in vitro. Method:The chemical constituents were isolated and purified by silica gel，Sephadex LH-20，ODS column chromatography and semi-preparative high performance liquid chromatography （HPLC）.the structures were identified by spectroscopy methods such as NMR and MS，as well as analysis of physicochemical properties and/or comparison with literature data，and the inhibitory activities of 13 compounds on HepG2 and SMMC-7721 cells were measured by methyl thiazolyl tetrazolium （MTT） method. Result:Thirteen known compounds were isolated and identified from 90% ethanol extract of Corydalis impatiens as ethyl-5-hydroxy-2-pyridinecarboxylate（1），coryhumolide（2），3，4-cis-3，4-dihydroxy-β-ionone（3），megastigmane（4），9-hydroxy-4，7-megastigmadien-3-one（5），blumenol A（6），indole-3-carboxy acid（7），1-methyl-[1，2，4]triazolo[4，3-b][1，2，4]triazin-7-one （8），adenine（9），nicotinamide（10），2-hydroxymethyl-5-pyridinol（11），adenosine（12）， and β-daucosterol（13）. Cytotoxicities assay showed that the IC₅₀ value of compound 3 for the hepatic cell line HepG2 was 24.7 μmol·L^-1 （positive control drug cisplatin：4.8 μmol·L^-1），and IC₅₀ value of compound 4 for the hepatic cell line SMMC-7721 was 13.8 μmol·L^-1（positive control drug cisplatin：5.4 μmol·L^-1）. Conclusion:Compound 1 was a new natural compound，compounds 3-8 were obtained from genus Corydalis for the first time，and compounds 2，9-12 were isolated from this plant for the first time. Compound 3 exhibited weak inhibitory effect on hepatic cell line HepG2，and compound 4 exhibited moderate inhibitory effect on hepatic cell line SMMC-7721.The other compounds rest of ones exhibited no obvious inhibitory effect on hepatic cell line HepG2 or SMMC-7721.