OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

Objective To investigate the impact of SARS-CoV-2 infection on male semen quality through meta-analysis and retrospec-tive study.Methods Literature retrieval was conducted in PubMed,CNKI,Wanfang Database and CBM database.Meta-analysis was performed using Stata 15.0.The male patients meeting the inclusion criteria from our hospital were enrolled as study subjects.General demographic data and semen parameters were collected.Single factor analysis of variance and graphing of semen parameters were con-ducted using GraphPad Prism 9.5.1.The test level was set at 0.05.Results A total of 9 studies involving 267 patients were included in the meta-analysis.There were no significant differences in sperm concentration and survival rate before and after SARS-CoV-2 infec-tion(P＞0.05).Semen volume and percentage of normal morphology significantly increased during 1-3 months after infection(P=0.005,P=0.010),with semen volume recovering to pre-infection level＞3 months later(P＞0.05).Sperm motility and progressive mo-tility increased＞3 months after infection(P=0.046,P=0.045),recovering to pre-infection levels(P=0.099,P=0.098).Sperm DNA fragmentation index may be temporarily elevated within 3 months after infection but gradually decreased＞3 months later.In the retrospective study of 8 cases,there were no statistical differences in semen parameters at different stages compared with pre-infection(P＞0.05),but semen parameters showed a negative trend during＜1 month after infection and recovered to pre-infection levels＞3 months later.Conclusion The results of this laboratory study are basically consistent with the meta-analysis.SARS-CoV-2 infection in males only caused short-term negative effects on sperm morphology,vitality and DNA integrity,but generally recovered to pre-infection levels＞3 months after infection.Due to the limitations of study subjects and sample size,the impact of SARS-CoV-2 infection on male semen quality needs to be further confirmed by long-term large-scale prospective studies.

Objective·To analyze infertility couples,dyadic coping level by using latent profile analysis(LPA),and explore the heterogeneity and related factors of different profiles.Methods·From September to November 2023,257 newly diagnosed infertility couples in pre-infertility treatment with assisted reproductive technology(ART)were recruited from Reproductive Medicine Center,Renji Hospital,Shanghai Jiao Tong University School of Medicine.All couples were evaluated by using general information questionnaire,Fertility Problem Inventory(FPI),Dyadic Coping Inventory(DCI),and Fertility Quality of Life(FertiQoL)Tool.LPA was used to explore the dyadic coping profiles of the couples before ART treatment,and general information,FPI scores and FertiQoL scores were compared among the profiles.Multinomial Logistic regression analysis was used to explore the related factors of different profiles.Results·A total of 257 couples with infertility were included,with an average age of(30.15±3.07)years for females,(31.82±3.82)years for males,(3.75±2.16)years for marriage,and(2.90±1.92)years for infertility;there were 118 couples caused by male infertility,109 couples caused by female infertility,and 30 couples caused by both infertility;the average DCI score for males was(128.25±19.15)points,while for females it was(129.91±18.32)points.According to the dyadic coping levels,the infertile couples were divided into four profiles:common positive coping group(153 couples,59.5％),common negative coping group(85 couples,33.1％),male positive coping group(12 couples,4.7％),and male negative coping group(7 couples,2.7％).There were statistically significant differences in the infertile couples'age,FPI score,FertiQoL score,and remarriage rate among the four profiles(P＜0.05).Multinomial Logistic regression analysis results showed that,with the common positive coping group as the reference,the common negative coping group had older men(OR=1.122,95％CI 1.004-1.254,P=0.036),higher FPI scores for both males and females(male:OR=1.019,95％CI 1.003-1.035,P=0.018;female:OR=1.020,95％CI 1.004-1.036,P=0.015),and lower FertiQol scores for males(OR=0.966,95％CI 0.937-0.996,P=0.029).Conclusion·There are four types of dyadic coping profiles in infertile couples before ART treatment.Compared with the common positive coping couples,higher reproductive pressure,elder age,and lower perceived fertility quality of life of males,and higher reproductive pressure of females are all risk factors for common negative coping couples.

ObjectiveTo evaluate the pharmacodynamic effect of Huangqintang （HQT） on ulcerative colitis （UC） model mice and investigate its protective effect against UC by regulating intestinal flora. MethodMale Balb/c mice were randomly divided into control group，model group， high-， medium-， and low-dose HQT groups （20， 10， 5 g·kg^-1）， flora interference group， flora interference model group， and flora interference-drug treatment group （HQT， 20 g·kg^-1）. The flora interference model was constructed through intragastric administration of antibiotics （200 mg·kg^-1 bacitracin and 200 mg·kg^-1 vancomycin） for 8 d， and the UC model was constructed by allowing mice with free access to 3% dextran sulfate sodium （DSS） solution for 7 d. HQT was administered for 7 d. After the experiments， the mice were sacrificed， and blood， colon， and feces were collected. Hematoxylin-eosin （HE） staining was performed to observe the colonic lesions. The serum levels of interleukin （IL）-4， IL-6， IL-10， and tumor necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of Claudin1， MUC1， Occludin， and zonula occludens-1（ZO-1） in colon tissues was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The fecal DNA of mice was extracted and analyzed by high-throughput sequencing. ResultCompared with the normal group， the model group showed increased serum content of IL-4， IL-6， and TNF-α （P<0.05， P<0.01） and decreased IL-10 （P<0.05）. Compared with the model group， the HQT groups displayed decreased serum levels of IL-4， IL-6， and TNF-α （P<0.05， P<0.01）， increased IL-10 content （P<0.01）， increased mRNA and protein expression levels of Claudin1， MUC1， Occludin， and ZO-1 （P<0.05， P<0.01）. After flora interference， the diversity and abundance of intestinal bacteria decreased. To be specific， Proteobacteria increased （P<0.01）， and Firmicutes and Bacteroidetes decreased （P<0.01）. After UC induction by DSS， Bacteroidetes and Tenericutes decreased （P<0.05）. The high-， medium-， and low-dose HQT groups showed increased Bacteroidetes and Tenericutes （P<0.05， P<0.01） and decreased Firmicutes （P<0.05）. Additionally， the abundance of Lactobacillus， Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Helicobacteris was positively proportional to the dose of HQT. ConclusionHQT can inhibit the inflammatory response of UC mice， restore the imbalance of intestinal flora， and repair the damaged intestinal mucosal barrier.

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.
Mice ; Animals ; Microcephaly/genetics* ; Autistic Disorder/metabolism* ; Autism Spectrum Disorder/metabolism* ; Nerve Tissue Proteins/metabolism* ; Brain/metabolism* ; Mice, Knockout ; Cell Cycle Proteins/metabolism*

Objective:To investigate the relationship between the expression level of lymphocyte enhancer-binding factor 1(LEF1) and CTNNB1 and the cycle arrest, apoptosis and radiation resistance of esophageal cancer cells and unravel the related mechanisms.Methods:Recombinantplasmids and empty plasmids expressing LEF1 and CTNNB1were constructed and transfected into esophageal cancer cells. RT-PCR assay was used to detect the transfection efficiency of the plasmids. Clone formation assay, CCK8 assay, cell cycle test by flow cytometry, apoptosis test by flow cytometry and Western blot were performed to detect the differences in theradioresistance, proliferation, cell cycle and apoptosis of esophageal cancer cells before and after transfection.Results:The survival rate of clonal colony cells in the pGEX-LEF1+ pCMV6-CTNNB1 group was significantly better than those in other groups ( P<0.05). The proliferation of clonal colony cellsat 72 h, 96 h and 120 h in the pGEX-LEF1+ pCMV6-CTNNB1 group was significantly better than those in the pGEX+ pCMV6, pGEX-LEF1+ pCMV6 and pCMV6-CTNNB1+ pGEX groups (all P<0.05). The percentage of G 2 phase arrest cells in the pGEX-LEF1+ pCMV6-CTNNB1 group was significantly higher than those in the other groups (all P<0.05). The apoptosis rate of esophageal cancer cells in the pGEX-LEF1+ pCMV6-CTNNB1 group was significantly lower compared with those in the pGEX+ pCMV6, pGEX-LEF1+ pCMV6 and pCMV6-CTNNB1+ pGEX groups (all P<0.05). The expression levels of Bax and Caspase 3 proteins in the pGEX-LEF1+ pCMV6-CTNNB1 group were significantly lower than those in the pGEX+ pCMV6, pGEX-LEF1+ pCMV6 and pCMV6-CTNNB1+ pGEX groups (all P<0.05). The expression level of Bcl-2 protein in the pGEX-LEF1+ pCMV6-CTNNB1 group was significantly higher compared with those in the other groups (all P<0.05). Conclusion:LEF1 and CTNNB1 can regulate the proliferation and G 2 phase arrest of esophageal cancer cells after radiation intervention by mediating the Wnt signaling pathway, and improve the radiation resistance of esophageal cancer cells by inhibiting cell apoptosis.

Objective:To observe the application and efficiency of Bushen Huoxue Plaster in senile subjects with diabetic kidney disease with Qi-Yin Deficiency with Blood stasis.Methods:A total of 100 elderly diabetic kidney disease(DKD)patients with Qi-Yin deficiency and Blood stasis syndrome in Endocrinology Department of Zhejiang Province Traditional Chinese and Western Medicine Hospital from February 2020 to May 2021were randomly divided into observation group(n=50)receiving TonifyingKidney and Activating Blood Paste plus TCM directional drug penetration therapy instrument for 10 days and control group(n=50)receiving placebo paste plus TCM directional drug penetration therapy instrument for 10 d. Main symptom score, overall syndrome score, urinary albumin/ creatinine ratio were observed and recorded.Results:After treatment, the observation group versus the control groups showed the statistically significant improvement in dry mouth and pharynx[(0.06±0.24)versus(0.30±0.68)score point, in feeling tired[(0.49±0.76)versus(0.98±1.02)score point], in spontaneous sweating or sweating after exercise[(0.08±0.27) vs.(0.32±0.69)score point], in limb numbness[(0.49±0.64) vs.(0.83±0.93)score point], in urination obstruction[(0.20±0.53) vs.(0.55±0.92)score point], and in total syndrome score[(1.65±2.06) vs.(3.36±2.53)score point, (all P<0.05)].The mean Ridit value of urinary albumin/creatinine ratio decreased in the observation group of chronic kidney disease stage A2 was 0.595 being higher than 0.405 in the control group, and the difference was statistically significant( P<0.05). Conclusions:The kidney-helping and blood-activating paste can improve the clinical symptoms of senile patients, and may have a certain effect on improving the urine albumin/creatinine ratio of patients with early diabetic kidney disease, and it is worthy of clinical application.

Objective:To analyze the research status of traditional Chinese Medicine (TCM) constitution identification for hypertension and discuss the research hotspots in this field.Methods:Based on China National Knowledge Infrastructure and Wanfang data knowledge service platform, the papers on TCM constitution identification of hypertension from 2010 to 2021 were retrieved. Bibliometric software Bicomb 2.01 and gCLUTO 1.0 were used to conduct a quantitative study of the retrieved literatures.Results:A total of 836 relevant articles were retrieved, and 42 high-frequency keywords such as "hypertension" "TCM constitution" "TCM constitution identification" and "phlegm-dampness constitution" were screened out. Research hotspots includes hypertension-TCM constitution identification, correlation between hypertension-TCM constitution and risk factors, hypertension-TCM differentiation of body and diet, hypertension-TCM body differentiation and treatment and hypertension-TCM health management.Conclusions:The number of papers on TCM constitution identification for hypertension is increasing year by year, but the regional development is uneven, the core author has not been formed, and there is less scientific research cooperation between regions.

Objective:To analyze the research status of traditional Chinese Medicine (TCM) constitution identification for hypertension and discuss the research hotspots in this field.Methods:Based on China National Knowledge Infrastructure and Wanfang data knowledge service platform, the papers on TCM constitution identification of hypertension from 2010 to 2021 were retrieved. Bibliometric software Bicomb 2.01 and gCLUTO 1.0 were used to conduct a quantitative study of the retrieved literatures.Results:A total of 836 relevant articles were retrieved, and 42 high-frequency keywords such as "hypertension" "TCM constitution" "TCM constitution identification" and "phlegm-dampness constitution" were screened out. Research hotspots includes hypertension-TCM constitution identification, correlation between hypertension-TCM constitution and risk factors, hypertension-TCM differentiation of body and diet, hypertension-TCM body differentiation and treatment and hypertension-TCM health management.Conclusions:The number of papers on TCM constitution identification for hypertension is increasing year by year, but the regional development is uneven, the core author has not been formed, and there is less scientific research cooperation between regions.

Objective:To explore the value of lactic acid (Lac), procalcitonin (PCT), sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluationⅡ (APACHEⅡ) score in assessing the severity and predicting the prognosis in sepsis shock.Methods:A retrospectively study was conducted. Patients with septic shock hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University from April 2015 to June 2019 were enrrolled. The patient's gender, age, body mass index (BMI), infection site, organ dysfunction status; Lac, PCT, C-reactive protein (CRP), heart rate and body temperature immediately after admission to the intensive care unit (ICU); APACHEⅡ and SOFA scores within 24 hours, and 28-day prognosis were collected. According to the 28-day prognosis, the patients with septic shock were divided into the survival group and the death group, and the differences in the indicators between the groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of 28-day death in patients with septic shock; receiver operating characteristic curve (ROC curve) was used to analyze the value of Lac, PCT, SOFA, APACHEⅡ, and age in predicting the 28-day prognosis of patients with septic shock.Results:A total of 303 septic shock patients were enrolled, of which 124 cases survived and 179 died on the 28th day, and the 28-day mortality was 59.08%. ① Compared with the survival group, patients in the death group were older (years old: 66.58±15.22 vs. 61.15±15.68), APACHEⅡ, SOFA, proportion of lung infections, Lac increased [APACHEⅡ score: 22.79±7.62 vs. 17.98±6.88, SOFA score: 9.42±3.51 vs. 5.65±1.59, proportion of lung infections: 53.63% (96/179) vs. 39.52% (49/124), Lac (mmol/L): 5.10±3.72 vs. 3.71±2.56], oxygenation index (PaO 2/FiO 2) and ICU body temperature decreased [PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 198.94±80.15 vs. 220.68±72.06, ICU body temperature (℃): 37.47±1.08 vs. 37.80±1.14], and the differences were statistically significant (all P < 0.05).②Multivariate Logistic regression analysis results: after adjusted for potential confounding factors, APACHEⅡ, PCT, Lac, age and SOFA were independent risk factors for death in patients with septic shock [APACHEⅡ: odds ratio ( OR) =1.05, 95% confidence interval (95% CI) was 1.01-1.10, P = 0.039; PCT: OR = 0.99, 95% CI was 0.98-1.00, P =0.012; Lac: OR = 1.23, 95% CI was 1.08-1.40, P = 0.002; age: OR = 1.03, 95% CI was 1.01-1.05, P =0.009; SOFA score: OR =1.88, 95% CI was 1.59-2.22, P < 0.001]. ③ROC curve analysis showed that APACHEⅡ, Lac, age and SOFA could predict the prognosis of patients with septic shock [APACHEⅡ: the area under the ROC curve (AUC) = 0.682 4, 95% CI was 0.621 7-0.743 1, P = 0.000; when the best cut-off value was 18.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 72.63%, 54.84%, 69.89%, 58.12%, 1.608 1 and 0.499 2, respectively. Lac: AUC = 0.604 5, 95% CI was 0.540 8-0.668 2, P = 0.002; when the best cut-off value was 3.550 mmol/L, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 50.84%, 73.39%, 73.39%, 50.94%, 1.910 3 and 0.669 9, respectively. Age: AUC = 0.599 1, 95% CI was 0.535 4-0.662 7, P = 0.003; when the best cut-off value was 72.500 years old, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 42.46%, 75.00%, 71.03%, 47.45%, 1.698 3 and 0.767 2, respectively. SOFA: AUC =0.822 3, 95% CI was 0.776 7-0.867 9, P = 0.000; when the best cut-off value was 7.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 68.72%, 87.90%, 89.13%, 66.06%, 5.680 4, 0.355 9 respectively]. The combined prediction had a good sensitivity (72.63%) and specificity (84.86%), and AUC (0.876 5) was higher than that of a single variable, suggested that the multivariate combination was more accurate in predicting the short-term outcome of septic shock. Conclusion:Lac, PCT, SOFA score, APACHEⅡ score and age were independent risk factors for death in patients with septic shock, and the accuracy of Lac, SOFA score, APACHEⅡ score and age in predicting short-term prognosis of septic shock was better than that of single variable, and the diagnostic value was higher.