ObjectiveTo investigate the association between single and combined exposure to arsenic （As）， mercury （Hg）， and cadmium （Cd） in urine and hearing loss in adults. MethodsA total of 400 adult patients were recruited for the study， comprising 200 participants in the normal hearing group and 200 in the hearing loss group. General demographic information of the study subjects was collected by a self-administered questionnaire， morning urine samples were tested for As， Hg， and Cd concentrations， and hearing status was assessed by Pure Tone Audiometry. A binary Logistic regression model was used to explore the association between the concentrations of the three metals in urine and hearing loss， and a Bayesian kernel-machine regression （BKMR） model was used to further explore the association between the concentrations of the three metal mixtures and hearing loss. ResultsAfter correction for urinary creatinine， As， Hg， and Cd concentrations were higher in the hearing loss group than those in the normal hearing group （P<0.05）. Binary Logistic regression indicated that concentrations of As， Hg， and Cd were positively associated with hearing loss， and the risk of hearing loss was significantly higher in the second quartile of Cd concentration compared to the first quartile （OR=2.000， 95%CI： 1.009-3.964）. BKMR modeling analysis showed that the combined exposure levels of As， Hg， and Cd significantly increased the risk of hearing loss， with Cd being the most important contributor （posterior inclusion probability=0.412）， and that there were potential interactions between As and Cd， and Cd and Hg. ConclusionCombined exposure to As， Hg， and Cd in urine is significantly associated with adult hearing loss， with Cd being the primary contributor in the exposure combination. The interactions between As and Cd， as well as Cd and Hg， may have adverse effects on hearing loss.

As antibiotic resistance becomes increasingly concerning,antimicrobial peptides,as a new type of antibiotic alternative,have attracted more attention.However,the low enzymatic stability of antimicrobial peptides severely limits their clinical applications.To address this issue,researchers have developed various structural modification strategies,including the introduction of unnatural amino acids,peptide chain cyclization and chemical group modification.This article reviews the basic principles and cases of the above modification strategies analyzes the advantages and disadvantages of different modification strategies and recommends ways these strategies can be optimized.In addition,this article predicts the developments of and potential challenges to strategies for enhancing enzymatic stability of antimicrobial peptides in the hope of providing references for subsequent research and development of antimicrobial peptides.

Objective·To evaluate the detection efficacy and clinical value of non-invasive prenatal testing(NIPT)for identifying copy number variations(CNVs)in the recurrent 17p12 region,including the peripheral myelin protein 22(PMP22)gene.Methods·Pregnant women who underwent NIPT in the International Peace Maternity & Child Health Hospital,Shanghai Jiao Tong University School of Medicine between July 2020 and April 2024 were enrolled.Clinical data of individuals indicated as high-risk for microdeletions/duplications in the 17p12 region based on NIPT results were collected.Follow-up was conducted to assess the results of subsequent prenatal diagnosis and chromosomal microarray analysis(CMA)performed on peripheral blood from both the pregnant women and their husband.The positive predictive value(PPV)of NIPT for detecting microdeletions/duplications in the 17p 12 region,as well as the underlying causes of false positives,was analyzed.Pregnancy outcomes and related clinical phenotypes of fetuses and pregnant women diagnosed with 17p12 CNVs were followed up.Results·A total of 61 858 pregnant women underwent NIPT testing.NIPT identified 24 cases(0.04％)as high-risk for CNVs in the 17p12 region,including six cases of high-risk 17p12 microduplication and 18 cases of high-risk 17p12 microdeletion.All 24 pregnant women received genetic counseling,and 21(87.50％)underwent invasive prenatal diagnosis.Invasive prenatal diagnostic confirmed four fetuses with 17p12 microduplications,nine fetuses with 17p12 microdeletions,and eight fetuses with no abnormalities,yielding a PPV of 61.90％(13/21).CMA analysis of maternal peripheral blood in the eight false-positive cases revealed that all mothers carried 17p12 CNVs.Further analysis of pregnant women with NIPT-indicated maternal CNVs revealed that all of them carried relevant CNVs.Among the 20 women with successful follow-up,the majority had normal deliveries,with only one case choosing to terminate the pregnancy due to a de-novo fetal 17p12 microduplication.Normally delivered fetuses(average age:1.5 years)were followed up without reporting any significant abnormalities.Of the 16 pregnant women carrying 17p12 CNVs,only two exhibited clinical phenotypes associated with these CNVs,while the others remained asymptomatic.Conclusion·NIPT demonstrates favorable detection efficacy for CNVs in the 17p12 region.Maternal CNVs are the primary cause of false-positive NIPT results for this region.

Objective:To investigate the clinical application value of expanded non-invasive prenatal testing(NIPT-plus)in screening for fetal chromosome copy number variations(CNV).Methods:From January 2021 to December 2023,141 pregnant women who voluntarily underwent amniocentesis at the Prenatal Diagnostic Centre of Urumqi Maternal and Child Health Hospital due to NIPT-plus suggesting a high risk of fetal CNV were selected.Amniotic fluid samples were collected for fetal chromosome karyotyping and chromosome microarray analysis(CMA).Pregnant women who underwent the above tests signed an informed consent form,and all cases were followed up forpregnancy outcome.Results:Among 141 NIPT-plus screen positive pregnant women,41 true posi-tive cases were detected by chromosomal karyotype analysis and CMA.The positive predictive value(PPV)for NIPT-plus screening for CNV was 29.08％(41/141).There was no statistically significant difference(P＞0.05)in the PPV of CNV detected by NIPT plus among different ages,indications and variant types.However,the PPV of CNV size＜10 Mb was significantly higher than that of CNV size≥ 10 Mb,and the difference was statistically signif-icant(39.62％vs.22.73％,P＜0.05).Among the 41 true positive cases,in addition to CNV,the CMA also detec-ted 7 cases of regions of Homozygosity(ROH),accounting for 17.07％(7/41)of the cases,two of which involved imprinted genes located on chromosomes 6 and 7.All continued pregnancy after genetic counselling and no signif-icant abnormalities were seen at neonatal follow-up after birth.Conclusions:NIPT-plus screening for fetal CNV has some clinical value,especially for CNV with fragment size＜10Mb,but accuracy needs to be further improved;CMA as a molecular diagnostic technique can detect ROH in cases where NIPT-plus suggests CNV abnormali-ties,and the combined use of the two techniques also opens new avenues for screening and diagnosis of prenatal imprinted diseases.

Objective:To investigate the mediating role of psychological capital between the perception of decent work and work engagement among Operating Room nurses, and to provide insights for improving their work engagement.Methods:From December 2023 to February 2024, a total of 307 Operating Room nurses from four class ⅢGrade A hospitals in Beijing, Chongqing, Dalian, and Zhuhai were recruited using convenience sampling. Data were collected using a general information questionnaire, Work Engagement Scale, Decent Work Scale, and Nurses' Psychological Capital Scale. Pearson correlation analysis was conducted to examine the relationships among psychological capital, perception of decent work, and work engagement. Structural equation modeling and mediation analysis were performed using AMOS 24.0 software.Results:A total of 307 questionnaires were distributed, and 301 valid responses were collected, with an effective response rate of 98.05%. The mean scores for work engagement, perception of decent work, and psychological capital were (41.01±10.76), (67.30±17.86), and (93.30±15.15), respectively. Work engagement was positively correlated with both the perception of decent work and psychological capital (all P<0.01), and the perception of decent work was positively correlated with psychological capital ( P<0.01). Psychological capital partially mediated the relationship between the perception of decent work and work engagement, with the mediating effect accounting for 62.63%. Conclusions:Psychological capital plays a partial mediating role between the perception of decent work and work engagement among Operating Room nurses. Nursing managers can enhance nurses' work engagement by improving their perception of decent work and strengthening their psychological capital.

Objective:To analyze the developmental trajectories of depressive symptoms in middle school students and their relationship with school connection and self-efficacy,and to provide evidence for the prevention of early adolescent depressive symptoms.Methods:In March(T1),June(T2),December(T3),809 middle school students were followed up in 2023 using the Patient Health Questionnaire-9(PHQ-9),School Connection Scale(SCS)and General Self-Efficacy Scale(GSES).The heterogeneity of the developmental trajectory of depressive symptoms in early adolescents was analyzed by the latent variable growth mixed model(LGMM),and the relation-ship between the developmental trajectory of depressive symptoms and school connection and self-efficacy was ana-lyzed by multiple logistic regression.Results:LGMM results showed that the development trajectory of early de-pressive symptoms in adolescents could be divided into:"low level-remission group"(65.3％),"low level-stable group"(28.6％)and"medium level-worsening group"(6.1％).Logistic regression analysis showed that male students(OR=0.62,95％CI=0.44-0.86)and school connection(OR=0.91,95％CI=0.88-0.94)were the protective factors in the"low level-stable group".Boys(OR=0.26,95％CI=0.13-0.53),school connection(OR=0.93,95％CI=0.88-0.98),and self-efficacy(OR=0.90,95％CI=0.85-0.96)were the protective fac-tors in the"medium level-worsening".Conclusion:There is heterogeneity in the developmental trajectory of early adolescent depressive symptoms,and school connection and self-efficacy are protective factors for the development of early adolescent depressive symptoms.

Objective To explore the value of radiomics model and deep learning model based on unenhanced MRI in predicting microvascular invasion(MVI)of hepatocellular carcinoma(HCC)preoperatively.Methods A total of 189 patients with postopera-tive pathologically confirmed HCC from two centers were retrospectively selected,of which 119 cases from Zhujiang Hospital of Southern Medical University were used as the training set[60 cases with negative MVI,59 cases with positive MVI],and 70 cases from Shenzhen People's Hospital were used as the external test set[38 cases with negative MVI and 32 cases with positive MVI].Clinical indicators were analyzed by univariate and multivariate logistic regression analysis and the independent predictors of positive MVI were screened.Deep transfer learning(DTL)and traditional radiomics methods were used to construct radiomics model and deep learning model based on unenhanced MRI.The predictive performances of each model were compared using receiver operating charac-teristic(ROC)curves and area under the curve(AUC).DeLong test was employed to compare statistical differences in performance of the models.Results Alkaline phosphatase(ALP)and prothrombin time(PT)were independent predictors of positive MVI(P<0.05).The deep learning model based on T2WI had the best predictive efficacy,with AUC of 0.779[95%confidence interval(CI)0.696-0.863]and 0.741(95%CI 0.620-0.861)in the training set and external test set,respectively,and there were statistically significant differences compared with the radiomics model and the clinical model based on T1WI(P<0.05).Conclusion Deep learning model based on T2WI has a certain application value in preoperative noninvasive prediction of MVI status in HCC patients.

Objective:To investigate the impact of circumferential tumor location (anterior wall, nonanterior wall, or circumferential) on circumferential resection margin (CRM) status, local recurrence, and survival in patients with mid-low rectal cancer.Methods:A retrospective cohort study was conducted using data from 696 patients with mid-low rectal adenocarcinoma who underwent surgery in the Department of Colorectal Surgery at the First Affiliated Hospital of Naval Medical University between December, 2018 and December, 2019. Based on MRI or contrast-enhanced CT findings, the rectal wall was divided into four quadrants: anterior, posterior, left, and right. Tumors were classified into three groups: anterior wall group ( n = 245), nonanterior wall group ( n = 286, tumors predominantly located on the posterior or lateral walls), and circumferential group ( n = 165, tumors involving ≥ 3/4 of the circumference). Propensity score matching (PSM) was used to balance baseline characteristics. Outcomes included pathological CRM positivity, local recurrence rate (LRR), overall survival (OS), and disease-free survival (DFS). Cox regression analysis was performed to identify risk factors for recurrence, and subgroup analysis was conducted in patients who did not receive neoadjuvant therapy. Results:After PSM, both the anterior and circumferential groups had significantly higher pathological CRM positivity rates compared to the nonanterior wall group ( P=0.040 and P=0.039, respectively). The median follow-up time was 64 months (range: 1-71 months). Compared to the nonanterior wall group, the anterior wall group also had a significantly higher 5-year LRR (8.8% vs. 2.3%, P=0.003), and significantly lower 5-year OS (80.7% vs. 91.6%, P=0.001) and DFS (76.6% vs. 84.6%, P=0.029). The circumferential group had a significantly higher 5-year LRR than the nonanterior wall group (11.4% vs. 3.8%, P=0.020), but no significant differences were observed in 5-year OS (81.8% vs. 89.5%, P=0.100) or DFS (70.7% vs. 78.3%, P=0.101). No significant differences were found between the anterior and circumferential groups in 5-year LRR (11.1% vs. 9.7%), OS (76.3% vs. 83.7%), or DFS (69.8% vs. 74.1%) either (all P>0.05). Cox univariate analysis and multivariate analysis identified anterior wall tumors (HR=3.751, 95%CI: 1.373-10.215, P=0.010), circumferential tumors (HR=3.240, 95%CI: 1.109-9.466, P=0.032), pathological CRM positivity (HR=3.071, 95%CI: 1.144-8.245, P=0.026), and lymph node metastasis (HR=2.584, 95%CI: 1.192-5.601, P=0.016) as independent risk factors for LRR. Conversely, a greater distance from tumor to the anal verge (per 1 cm increase, HR=0.831, 95%CI: 0.712-0.970, P=0.019), and neoadjuvant therapy (HR=0.442, 95%CI: 0.204-0.957, P=0.038) were identified as independent protective factors against LRR. In patients who did not receive neoadjuvant therapy, locally advanced nonanterior wall tumors exhibited markedly low LRR (1.3% for pathological stage II-III, 1.6% for pT3-4 stage). Conclusion:Rectal tumors located in the anterior wall or involving the circumference are associated with higher CRM positivity rates, increased local recurrence, and poorer survival. These patients should be prioritized for neoadjuvant therapy. In contrast, nonanterior wall tumors have a low recurrence rate, and selective omission of neoadjuvant therapy may be considered for these cases.

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Objective: To explore the latent class characteristics and related factors of health risk behaviors among higher vocational college students (referred to as vocational students) in the Wuling Mountain Area, so as to provide references for promoting their healthy development and formulating effective intervention measures. Methods: From April to June 2024, a stratified random cluster sampling method was used to survey 1 737 students from three higher vocational colleges in the Wuling Mountain Area (Xiangxi in Hunan, Enshi in Hubei, and Tongren in Guizhou). The study employed the Health risk Behavior Questionnaire for College Students, the Parent-Child Relationship Scale, the Social Support Scale, and the School Connection Scale for data collection. Latent class analysis (LCA) was used to examine the heterogeneous distribution characteristics of health risk behaviors among vocational students, and multivariate Logistic regression was applied to analyze the related factors of latent classes. Results: The LCA results identified three latent classes based on 12 health risk behaviors: the comprehensive high risk group (151 students, 8.7% ), the psychological distress group (883 students, 50.8%), and the low risk group (703 students, 40.5%). The distribution of latent classes showed statistically significant differences in gender and only child status ( χ 2=121.25, 9.85, both P <0.05). The low risk group scored higher in parent-child relationship (29.26±6.19), social support (63.98±18.16), and school connection (35.97± 7.71 ) compared to the comprehensive high risk group (27.28±6.03, 57.67±15.60, 32.97±7.55) and the psychological distress group (27.52±5.19, 62.06±14.54, 33.80±6.14) ( F =20.37, 23.51, 9.89, all P <0.05). Multivariate Logistic regression revealed that boys( OR =3.29) were more likely to belong to the comprehensive high risk group, social support ( OR =0.03, 0.21) and school connection ( OR =0.92, 0.96) were less likely to belong to both the comprehensive high risk and psychological distress groups (all P < 0.05). Conclusions There are three potential categories of healthharmful behaviors among vocational college students in Wuling Mountain Area. Schools, families and society should enhance the levels of parent-child relationship, school connections and social support for vocational college students of different categories to promote their physical and mental health development.