Objective:To investigate the expression of Neurexophilin 4(NXPH4)in hepatocellular carcinoma(HCC)and its clinical significance and function.Methods:Retrieved LIHC project data(mRNA expression profiles and clinical records)from TCGA,analyzed differential NXPH4 expression in HCC versus adjacent non-tumor tissues,and investi-gated correlations between NXPH4 expression and clinicopathological characteristics/prognostic outcomes in HCC.Using GOEA and GSEA to investigate potential biological functions of NXPH4 in hepatocellular carcinoma.Results:NXPH4 exhibited significant upregulation in 23 cancer types(P<0.05),with significant associations to advanced HCC progression markers including TNM stage(P<0.05),histologic grade(P<0.05),and vascular invasion(P<0.05).Clinically,elevated NXPH4 expression correlated with reduced OS(HR=1.64,95%CI:1.15-2.33,P=0.006)and DSS(HR=1.88,95%CI:1.19-2.96,P=0.007).The immune infiltration results showed that NXPH4 expression was significantly correlated with Th2 cells and Th17 cells(all P values<0.05).Furthermore,NXPH4 expression was positively correlated with the levels of several immune checkpoint markers:TIGIT(r=0.265),PD-1(r=0.297),CTLA-4(r=0.302),and LAG-3(r=0.179,all P<0.001).Gene enrichment analysis revealed NXPH4 was significantly enriched in:pattern specification process(P<0.001);receptor ligand activity(P<0.001);collagen formation(P=0.009);activation of matrix metalloproteinases(P<0.001);neuro-active ligand receptor interactions(P<0.001);and ALK2 signaling(P=0.039).Conclusion:NXPH4 is associated with clinical pathological staging and poor prognosis in HCC patients;NXPH4 is associated with oncogenic pathways and im-mune infiltration,and has high value in predicting patient prognosis and immunotherapy.

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective:To investigate the expression of Neurexophilin 4(NXPH4)in hepatocellular carcinoma(HCC)and its clinical significance and function.Methods:Retrieved LIHC project data(mRNA expression profiles and clinical records)from TCGA,analyzed differential NXPH4 expression in HCC versus adjacent non-tumor tissues,and investi-gated correlations between NXPH4 expression and clinicopathological characteristics/prognostic outcomes in HCC.Using GOEA and GSEA to investigate potential biological functions of NXPH4 in hepatocellular carcinoma.Results:NXPH4 exhibited significant upregulation in 23 cancer types(P<0.05),with significant associations to advanced HCC progression markers including TNM stage(P<0.05),histologic grade(P<0.05),and vascular invasion(P<0.05).Clinically,elevated NXPH4 expression correlated with reduced OS(HR=1.64,95%CI:1.15-2.33,P=0.006)and DSS(HR=1.88,95%CI:1.19-2.96,P=0.007).The immune infiltration results showed that NXPH4 expression was significantly correlated with Th2 cells and Th17 cells(all P values<0.05).Furthermore,NXPH4 expression was positively correlated with the levels of several immune checkpoint markers:TIGIT(r=0.265),PD-1(r=0.297),CTLA-4(r=0.302),and LAG-3(r=0.179,all P<0.001).Gene enrichment analysis revealed NXPH4 was significantly enriched in:pattern specification process(P<0.001);receptor ligand activity(P<0.001);collagen formation(P=0.009);activation of matrix metalloproteinases(P<0.001);neuro-active ligand receptor interactions(P<0.001);and ALK2 signaling(P=0.039).Conclusion:NXPH4 is associated with clinical pathological staging and poor prognosis in HCC patients;NXPH4 is associated with oncogenic pathways and im-mune infiltration,and has high value in predicting patient prognosis and immunotherapy.

Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.

Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P＜0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P＜0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P＜0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1％).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2％vs.83.8％vs.91.6％,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.

Epilepsy is a common neurological disease,has the characteristics of recurrent attacks and long-term treatment,thus bringing great pressure to patients and their families.Therefore,it is particularly important to do a good job of disability assessment.In recent years,with the development of the discipline,academic organizations such as the International League Against Epilepsy(ILAE)and China Association Against Epilepsy(CAAE)have successively updated the definition and diagnostic criteria of epilepsy and seizures.However,some items of epilepsy in the current Criteria for Disability Rating of Military Personnel(Trial)issued by People's Liberation Army(PLA)in 2011 can no longer meet the latest guidelines at home and abroad.Therefore,we suggest that the items related to epilepsy in the Criteria for Disability Rating of Military Personnel(Trial)should be revised to ensure that the disability evaluation being completed fairly and successfully.