Objective: To explore the relationship between socio ecological risk factors (SERF), physical activity (PA) developmental trajectories, and depressive symptoms among junior and senior high school students in Tianjin, in order to provide theoretical support for comprehensive interventions for adolescent depression. Methods: A longitudinal follow up design was adopted. In September 2022, a baseline survey was conducted using a stratified cluster random sampling method in two junior high schools and two senior high schools in Tianjin, collecting data on students basic information, SERF, PA, and depressive symptoms. Two follow up surveys were conducted in September 2023 and 2024, yielding 588 valid participants. Latent class growth analysis (LCGA) was used to identify PA developmental trajectory categories among junior and senior high school students. Logistic regression was applied to examine the associations between depressive symptoms and SERF as well as PA trajectories. Results: The detection rates of depressive symptoms among Tianjin junior and senior high school students over the three years were 26.53%, 20.24%, and 21.26 %, respectively. Depressive symptoms were positively correlated with SERF ( OR=1.04, 95%CI=1.03-1.05, P <0.05). The highest risks were observed in the individual dimension and family dimension ( OR =1.28, 1.21, both P <0.05). LCGA identified three PA trajectory groups:persistently low level (80.65%), persistently high level (4.58%), and slowly increasing group ( 14.77 %). Multivariate regression analysis showed that compared with the persistently low level PA, the slowly increasing PA significantly reduced the risk of depressive symptoms ( OR=0.44, 95%CI =0.20-0.88), while SERF still increased the risk of depressive symptoms ( OR=1.04, 95%CI =1.03-1.05) (both P <0.05). Conclusion SERF are risk factors for depression symptoms among junior and senior high school students, whereas slowly increasing PA development trajectory demonstrates a protective effect.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective To investigate the mortality and risk factors of HIV-infected patients complicated with progressive multifocal leukoencephalopathy(PML)to inform the outcomes of these patients.Methods The clinical data of people living with HIV related PML who were treated at Chongqing Public Health Medical Treatment Center from January 1,2019 to December 31,2023 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.Log-rank test was performed.Cox regression model was used for multivariate analysis.Results A total of 42 people living with HIV related PML were enrolled,including 34 males(81.0％).The median age was 44.5(36.3,51.0)years.PML was confirmed in 76.2％(32/42)of patients,and possible PML was diagnosed in 23.8％(10/42)of patients.The median time to diagnosis was 32.5(14.8,58.3)days.The median CD4+T cell count was 69.0(39.8,112.0)cells/μL.The median HIV viral load was 5.05(2.62,5.77)log10 copies/mL.The overall mortality rate was 54.8％(23/42)for patients with HIV related PML.CD4+T cell count ≤50 cells/μL and initial modified Rankin scale(mRS)score ≥4 points were independent risk factors for the overall mortality of people living with HIV related PML(P＜0.05).Conclusions People living with HIV related PML have a high mortality rate.Low CD4+T cell count and high initial mRS score were independent risk factors for the mortality of patients with HIV related PML.Currently,no definitive and effective drug treatment is available for PML.Early detection,diagnosis and initiation of antiretroviral therapy may improve the outcomes of patients.

Objective:We summarize the clinical characteristics of surgeries in which the thyroid lobe is used as a transfer flap to treat early pharyngeal fistula following total laryngectomy.We also provide useful data for improving the diagnosis and management of this condition.Methods:Retrospective analysis was conducted on data from 8 patients with pharyngocutaneous fistulas after total laryngectomy for laryn-geal and pharyngeal cancer patients admitted to Hunan Provincial People's Hospital(The First Hospital Affiliated to Hunan Normal University)between October 2016 and October 2023.The surgeons performed a double-layer repair technique that included local inversion and a purse-string suture of the fistula using the thyroid lobe as a transfer flap.Clinical data were collected to analyze postoperative outcomes.Results:All eight patients experienced successful pharyngeal fistula repair.Postoperatively,these patients were managed with nasogastric tube feed-ing,liquid diet,and prophylactic antibiotics to prevent infection.After 10 days,their diet was changed to oral liquids,and their nasogastric tubes were removed.All patients were discharged after complete recovery.Conclusions:Use of the thyroid lobe as a transfer flap in a double-layer repair technique involving local inversion of the fistula is an effective method for repairing early pharyngeal fistula after total laryngectomy.This approach offers several advantages,including ease of flap harvesting,shortened operation time,reduced patient discom-fort,high transfer flap survival rate,and rapid postoperative recovery.The clinical efficacy of this technique is well-supported,making it a re-liable option for the management of early pharyngeal leaks.

OBJECTIVE To establish a visualized loop-mediated isothermal amplification(LAMP)for rapid detec-tion of Klebsiella pneumoniae and evaluate the sensitivity and specificity of the detection method.METHODS To-tally4 specific LAMP primers were designed by targeting to rcsA gene of the K.pneumoniae.The reaction condi-tions(temperature,time)and the parameters of the reaction system were optimized,the reaction was made visu-alized by using chimeric fluorescent dye SYBR Green Ⅰ.The optimal reactions conditions and reaction systems were determined based on the results of visualization and agarose gel electrophoresis.The optimized conditions and systems were used to test the sensitivity by diluting DNA template on a 10-fold gradient,meanwhile,the specifici-ty of the method was evaluated by detecting K.pneumoniae and other ten species of common bacteria and fungi.RESULTS The optimal reaction temperature was 63 ℃ after the optimization,with the reaction time 35 min;the concentration of buffer solution in the reaction system was determined as 0.8×,with the concentration of magne-sium ion 8 mmol/L,the concentration of dNTPs 1.4 mmol/L,the ratio of internal to external primers 6∶1,the concentration of Bst DNA polymerase 0.32 U/μl,the concentration of betaine 0.75 mmol/L.For the test of sensi-tivity,the method could detect the template with the concentration of 1.5 ng/μl.For the test of specificity,only the detection of K.pneumoniae could display positive visualized result and positive electrophoretic band.CONCLUSIONS The visualized LAMP with high specificity and sensitivity for rapid detection of K.pneumoniae is successfully established,facilitating the observation of the detection result without the use of precise instruments.It is suitable for the detection in grass-root laboratories after successful preliminary application in clinical detection.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Objective:To evaluate the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) combined with low molecular weight heparin (LMWH) on lower limb deep vein thrombosis (DVT) after fracture fixation in aged rabbits.Methods:Thirty-two elderly New Zealand rabbits of either sex, aged 36 months, weighing 3.5-4.0 kg, were divided into 4 groups ( n=8 each) using the random number table method: control group (C group), fracture fixation group (F group), low molecular weight heparin group (L group) and BZYQT combined with LMWH group (BL group). A model of fixation surgery for right femoral shaft fracture was established in anesthetized rabbits in F, L and BL groups. Starting from postoperative day 1, BL group received BZYQT at 3.6 ml/kg via gavage, F and L groups received normal saline at 3.6 ml/kg via gavage, L and BL groups received subcutaneous injection of LMWH at 200 IU/kg, and all the administrations were performed daily at 08: 00 for 7 consecutive days. On postoperative day 7, ultrasound examination was performed to assess lower limb DVT. Blood samples were collected from the marginal ear vein for determination of the serum concentrations of cortisol (COR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and endothelin-1 (ET-1) by enzyme-linked immunosorbent assay. Femoral vein specimens were obtained under anesthesia for microscopic examination of the pathological changes of the femoral vein lumen and endothelial tissues (by HE staining) and of the morphology of vascular endothelial cells (by the transmission electron microscopy). Results:Compared with C group, the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly increased in F, L and BL groups, and the incidence of lower limb DVT within 7 days after surgery was significantly increased in F and L groups ( P<0.05). Compared with F group, the incidence of lower limb DVT within 7 days after surgery was significantly decreased in L and BL groups, and the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly decreased ( P<0.05), and the pathological damage was significantly reduced in BL group. Compared with L group, the incidence of lower limb DVT and concentration of IL-6 were significantly decreased ( P<0.05), and pathological damage was significantly alleviated in BL group. Conclusions:BZYQT combined with LMWH can prevent the occurrence of lower limb DVT after fracture fixation in aged rabbits.

Objective To investigate the mortality and risk factors of HIV-infected patients complicated with progressive multifocal leukoencephalopathy(PML)to inform the outcomes of these patients.Methods The clinical data of people living with HIV related PML who were treated at Chongqing Public Health Medical Treatment Center from January 1,2019 to December 31,2023 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.Log-rank test was performed.Cox regression model was used for multivariate analysis.Results A total of 42 people living with HIV related PML were enrolled,including 34 males(81.0％).The median age was 44.5(36.3,51.0)years.PML was confirmed in 76.2％(32/42)of patients,and possible PML was diagnosed in 23.8％(10/42)of patients.The median time to diagnosis was 32.5(14.8,58.3)days.The median CD4+T cell count was 69.0(39.8,112.0)cells/μL.The median HIV viral load was 5.05(2.62,5.77)log10 copies/mL.The overall mortality rate was 54.8％(23/42)for patients with HIV related PML.CD4+T cell count ≤50 cells/μL and initial modified Rankin scale(mRS)score ≥4 points were independent risk factors for the overall mortality of people living with HIV related PML(P＜0.05).Conclusions People living with HIV related PML have a high mortality rate.Low CD4+T cell count and high initial mRS score were independent risk factors for the mortality of patients with HIV related PML.Currently,no definitive and effective drug treatment is available for PML.Early detection,diagnosis and initiation of antiretroviral therapy may improve the outcomes of patients.

Objective:To understand the occurrence of different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City and analyze the cumulative effects of lifestyle on these patterns of multimorbidity.Methods:From September to November 2022, a stratified cluster random sampling method was used to select students from primary schools, junior high schools, general high schools, and vocational schools in 16 districts of Tianjin to screen for height, weight, blood pressure, distant vision, and diopter. One year later, a follow-up measurement and questionnaire survey were conducted. The log-binomial model was used to analyze the strength of the association between lifestyle factors and different patterns of multimorbidity.Results:The age of 9 488 students was (12.37±2.49) years old, including 4 999 boys and 4 489 girls. The detection rates of three patterns of multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia were 6.63%, 9.32%, and 4.21%, respectively. The detection rates of the three types of multimorbidity in boys were higher than those in girls (all P<0.001). The detection rate of overweight obesity and high blood pressure in suburban areas was higher than that in urban areas ( P=0.002). The detection rate of overweight obesity and myopia in suburban areas was lower than that in urban areas ( P=0.034). The detection rate of overweight obesity and myopia among those aged 9-12 years old was higher than other age groups (all P<0.001). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity and high blood pressure was 0.79 (0.68-0.92). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity with high blood pressure and myopia was 0.82 (0.67-0.99). Compared with children and adolescents with 0-2 favorable lifestyle factors, those with 4-5 favorable lifestyle factors had a lower risk of overweight obesity and high blood pressure ( ARR=0.84, 95% CI: 0.59-0.92). Conclusion:Boys aged 9-18 in Tianjin City are more prone to multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia. Children and adolescents with 4-5 favorable lifestyle factors have a reduced risk of occurrence of overweight obesity and high blood pressure. Lifestyle has cumulative effects on multimorbidity of overweight obesity and high blood pressure.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.