Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To compare the differences in lower limb force line between degenerative medial meniscus injuries and lateral meniscus injuries and investigate their correlation.Methods A total of 90 patients who underwent arthroscopic treatment for meniscal injuries between March 2019 and March 2022 were enrolled in the study.They were 45 males and 45 females,at a median age of 52 years(ranging from 40 to 59 years).Of these patients,47 had medial meniscus injuries,while 43 had lateral meniscus injuries.The hip-knee-ankle(HKA)angle was measured on full-length films,and the differences were compared between the 2 groups.Results There were no significant differences in terms of gender,age,lower limb laterality,body mass index,site of injury,and type of injury between the medial meniscus injury group and the lateral meniscus injury group.Statistical difference was observed in the mean HKA angle,with a value of(177.20±2.46)° in the medial meniscus injury group and of(181.05±3.13)° in the lateral meniscus injury group(P＜0.01).Conclusion There is a significant difference in HKA angle between medial meniscus injury group and the lateral meniscus injury group.A correlation is found between lower limb alignment and degenerative meniscus injury.

【Objective】 To compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.

[Objective] To explore the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou, and to investigate the correlation between donation frequency and these factors. [Methods] A cross-sectional study was conducted among 13 042 whole blood donors from 17 street blood donation sites of Guangzhou Blood Center from May to August 2020. Descriptive analysis was used to describe the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou. Ordinal multinomial logistic regression model was used to analyze the correlation between donation frequency and these factors. [Results] It was found that some of 13 042 blood donors had unhealthy habits, such as 6.8% (698/10 214，2 828 missing values) had severe tobacco dependence, 30.6% (3 997/13 042) had low exercise levels, 38.8%（5 056/13 042）had poor sleep quality, and 2.2% (271/12 159，883 missing values) had alcohol dependence. In addition, 2.8% (364/13 042) and 1.3% (172/13 042) of the donors may have moderate to severe depression and anxiety symptoms, respectively. The results of the ordinal multinomial logistic regression model showed that exercise level was significantly negatively correlated with the degree of depression and anxiety among blood donors. With the decrease in exercise level, the possibility of depression and anxiety among donors increased significantly. BMI, household income, education level, marital status, donation frequency, alcohol consumption and smoking had no significant correlation with the mental health status of donors. [Conclusion] Improving the exercise habits of blood donors may help enhance their mental health level. It is recommended that blood station staff strengthen the content of exercise when providing health education to blood donors to maintain a healthy lifestyle. It also suggests that there may be a certain degree of under-diagnosis of mental health problems in the process of health consultation before blood donation, and conducting more comprehensive and effective mental health assessments for blood donors is recommended.

Objective To explore the clinical value of endoscopic ultrasonography(EUS)combined with serum serine protease inhibitor Kazal 1(SPINK1)and secretory phosphoprotein 1(SPP1)in early diagnosis of esophageal cancer.Methods 276 patients from June 2021 to May 2023 were selected as the study objects.92 cases of esophageal cancer diagnosed by operation and pathology were esophageal cancer group,another 89 patients diagnosed as benign esophageal lesions through tissue biopsy were selected as the benign lesion group,and 95 healthy individuals who underwent physical examinations were collected as the healthy control group,general information such as age and gender of subjects in three groups were collected and organized;using pathological results as the gold standard,the accuracy of EUS in diagnosing esophageal cancer was verified;the expression of serum SPINK1 and SPP1 was compared among the esophageal cancer group,benign lesion group,and healthy control group;the relationship between the expression of serum SPINK1 and SPP1 in esophageal cancer patients and their clinical and pathological characteristics was explored;efficacy of EUS combined with serum SPINK1,SPP1 levels for early diagnosis of esophageal cancer was analyzed using receiver operator characteristic curve(ROC curve).Results Compared with the gold standard,the results of EUS examination showed that 81 cases were diagnosed with esophageal cancer,79 cases were diagnosed with benign lesions,11 cases were missed diagnosed,and 10 cases were misdiagnosed,with an accuracy rate of 88.40%(160/181);Compared with the healthy control group and the benign lesion group,the expression levels of serum SPINK1 and SPP1 in the esophageal cancer group were obviously increased,the expression levels of serum SPINK1 and SPP1 in the benign lesion group were significantly higher than those in the healthy control group,the differences were statistically significant(P<0.05);Serum SPINK1 expression was linked to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and tissue grading level 3 in patients(P<0.05).Serum SPP1 expression level was related to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and estrogen receptor positivity of patients(P<0.05);ROC curve showed that the area under the curve(AUC)of EUS,serum SPINK1,SPP1 levels,and their combination in the early diagnosis of esophageal cancer was 0.862,0.834,0.782,and 0.926,respectively,the clinical efficacy of the combination of the three in the early diagnosis of esophageal cancer was superior to that of EUS,serum SPINK1,and SPP1 alone(Z=2.30,Z=3.70,Z=4.23,P=0.022,P=0.000,P=0.000).Conclusion The expression levels of serum SPINK1 and SPP1 in esophageal cancer patients are abnormally up-regulated.The combination of EUS and serum SPINK1 and SPP1 has high clinical value in early diagnosis of esophageal cancer.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Objective To explore the value of controlling nutritional status(CONUT)score and related inflammatory indicators in predicting the prognosis of clear cell renal cell carcinoma(ccRCC)patients,to provide a reference for better clinical assessment and individualized treatment plan.Methods A retrospective study was conducted on 132 patients with ccRCC admitted to four comprehensive hospitals in Yibin during 2010 and 2018.Patients'medical and follow-up records were collected,and receiver operating characteristic(ROC)curve was drawn to analyze the area under the curve(AUC)and optimal cut-off value of CONUT score and related indicators.Survival curve was plotted with Kaplan-Meier method,and the influencing factors of prognosis were analyzed with Log-rank test and Cox regression.Results During the follow-up of 62(53,71)months,37(28.03％)deaths occurred.The disease-specific survival(DSS)and progression-free survival(PFS)were 51(41,58)and 46(35,56)months,respectively.The 3-year and 5-year DSS and PFS were 84.09％and 71.97％,and 75.00％and 71.97％,respectively.The AUC of CONUT score,neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and lymphocyte to monocyte ratio(LMR)were 0.980,0.905,0.899 and 0.884,respectively,with the optimal cut-off values of 3.50,3.19,89.07 and 3.56,respectively.Cox regression showed that CONUT score(HR=0.042,95％CI:0.013-0.140)and PLR(HR=0.182,95％CI:0.045-0.744)were associated with DSS;CONUT score(HR=0.029,95％CI:0.010-0.086)and LMR(HR=2.984,95％CI:1.227-7.258)were associated with PFS.Conclusion The prognosis of ccRCC patients is related to their nutritional,immune,and inflammatory status.CONUT score and inflammatory factors(PLR,LMR)may be important predictors of DSS and PFS.