Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective To identify key influencing factors for comorbidity between myopia and depressive symptoms among middle school students, and to construct a nomogram predictive model capable of quantitatively assessing their comorbidity risk. Methods A total of 13 976 middle school students aged 11-20 from 14 counties (cities, districts) in Yichang City were selected as study subjects through cluster random sampling. On-site surveys were conducted using the Student Health Status and Influencing Factors Questionnaire and the Depression Assessment Scale. Chi-square test and multivariate logistic regression analysis were employed to investigate the comorbidity association between myopia and depressive symptoms and their influencing factors, and to construct a nomogram model for risk prediction. Results The myopia screening rate among middle school students was 68.67%, the depression detection rate was 23.31%, and the comorbidity detection rate was 16.59%. Logistic regression analysis revealed that boarding school (OR=1.207), smoking history (OR=1.504), alcohol consumption (OR=2.016), outdoor activity time <1 h (OR=1.293), internet addiction (OR=4.008), school bullying (OR=4.358), school absence due to illness within one year (OR=1.712), and severe injury within one year (OR=1.356) were risk factors for myopia-depression comorbidity. Protective factors included male gender (OR=0.578), junior high school students (OR=0.670), nuclear family (OR=0.862), moderate-to-high intensity exercise ≥1 h/d (OR=0.852), screen time <2h (OR=0.803), adequate sleep duration (OR=0.602), and homework time after school <2 h/d (OR=0.766). The nomogram model constructed based on the above variables exhibited excellent discriminant power (AUC = 0.712) and calibration (Hosmer-Lemeshow test, χ²=3.245, P> 0.05). Conclusion Factors such as boarding school attendance, smoking history, alcohol consumption, less than 1 hour of daily outdoor activity, internet addiction, and school bullying are significantly associated with the comorbidity of screening myopia and depressive symptoms among middle school students in Yichang City. The nomogram model effectively predicts the comorbidity risk in this population, facilitating timely intervention for high-risk individuals.

Objective: To examine the association between health behaviors and depressive symptoms among junior and senior high school students, so as to provide evidence for combined behavioral interventions targeting adolescent mental health. Methods: From September to November 2023, a stratified cluster random sampling method was used to recruit 104 834 junior and senior high school students from all 13 prefecture level cities (124 districts/counties) in Heilongjiang Province, China. Multivariable Logistic regression models, as well as multiplicative and additive interaction analyses were employed to analyze the associations between health behaviors and depressive symptoms, and Chi-square tests for trend were conducted to explore ,the changing tendency in the risk of depressive symptoms with increasing numbers of health behaviors among junior and senior high school students. Results: Healthy diet ( OR =0.66, 95% CI =0.63-0.68), healthy physical activity ( OR =0.47, 95% CI =0.45-0.49), healthy outdoor activity ( OR =0.55, 95% CI =0.52-0.57), healthy sleep ( OR =0.72, 95% CI =0.69-0.75), and healthy screen use ( OR =0.79, 95% CI =0.76-0.82) were independently associated with lower rates of depressive symptoms (all P <0.01). The risk of depressive symptoms decreased progressively with an increasing cumulative number of health behaviors ( χ 2 trend =996.73, P <0.01). Except for the interaction between healthy diet and healthy sleep, significant additive interactions were observed among the remaining health behaviors( RERI =0.07-0.23,all P <0.05). The probability of depressive symptoms was lower among girls with 2-3 healthy behaviors than among boys ( Z =2.51, 2.65), lower among urban students with 2-3 healthy behaviors than among suburban county students ( Z =-2.36, -2.04), and lower among senior high school students with 2-4 healthy behaviors than among junior high school students ( Z =2.17, 2.10, 2.04) (all P <0.05). Conclusions Health behaviors are significantly associated with depressive symptoms among junior and senior high school students. The probability of depressive symptoms is lower among girls, urban students, and senior high school students who engage in multiple healthy behaviors. Implementing combined interventions targeting multiple health behaviors in these populations may yield greater benefits.

In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

Since the beginning of the new century, advances in understanding the intricate interactions between oncology and the immune system have accelerated the rapid development of immune checkpoint inhibitors for the treatment of non-small cell lung cancer. However, resistance to immunotherapy is inevitable. Therefore, uncovering the mechanisms of immunotherapy resistance, proposing strategies to overcome resistance, and identifying future research directions are imperative. Given the limitations of space in each article, this review will explore the complex mechanisms underlying immunotherapy resistance. These mechanisms involve almost all cell types within the body, excluding foreign cancer cells. Notably, these cells serve as recipients (either inhibitory or stimulatory, or both) and producers of signals, playing different roles in various contexts. At the molecular level, these mechanisms include genetic and epigenetic abnormalities in all cells within the microenvironment, as well as the influence of a variety of protein kinase, growth factors, and cytokines with temporal and spatial heterogeneity. At the macroscopic level, host factors such as nutritional metabolism, comorbidities, and microbiota within the organs, as well as neuro-psychological regulation, influence the efficacy of immunotherapy.

Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

Objective To systematically evaluate the effectiveness of acupuncture in treating chronic cough and analyze its acupoint selection patterns.Methods Randomized controlled trials(RCTs)on acupuncture for chronic cough were retrieved from databases including CNKI,VIP,Wan Fang Data,CBM,PubMed,and Web of Science,Cochrane Library and Embase from their inception to April 2025.Original data from the included studies were extracted.Meta-analysis was performed to compare the acupuncture treatment group with the western medicine control group[using leukotriene receptor antagonists(LTRAs)and/or glucocorticoids]on outcomes including cough symptom scores,serum tumor necrosis factor-α(TNF-α)levels,pulmonary function indicators[forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1)],overall clinical effectiveness,and incidence of adverse reactions.Publication bias was assessed using funnel plots,and descriptive analysis of the acupoint prescriptions from the included studies was conducted using Rstudio software to summarize the patterns of acupoint selection for chronic cough.Results A total of 10 studies involving 806 patients were included.Meta-analysis results showed that acupuncture was superior to the western medicine control group in improving cough symptom scores,reducing serum TNF-α levels,enhancing pulmonary function(FVC and FEV1),increasing overall clinical effectiveness,and reducing adverse reactions,with statistically significant differences.Further analysis of the 10 included studies revealed that the most frequently used acupoints were Feishu(BL13)(n=9 times),Zusanli(ST36)(n=7 times),Lieque(LU7)(n=6 times),and Pishu(BL20)(n=5 times).The most frequently utilized meridians were the Bladder Meridian of Foot-Taiyang(BL)(n=10 times),the Stomach Meridian of Foot-Yangming(ST)(n=7 times),and the Lung Meridian of Hand-Taiyin(LU)(n=7 times).Acupoints were primarily located on the lower back(36.92%),upper limbs(26.15%),and lower limbs(21.53%).Conclusion Acupuncture is effective in treating chronic cough.The acupoint prescriptions for chronic cough should follow the principles of symptomatic point selection and anterior-posterior point pairing,emphasizing the back-shu and front-mu point pairing method,as well as the upper-lower point pairing method.Points are predominantly selected from the Bladder meridian(BL),lung meridian(LU),and stomach meridian(ST).

Objective:To investigate the efficacy of naloxone in improving health-related quality of life in patients with chronic arsenic exposure-related pruritus, and to explore the modification effect of gene polymorphisms associated with arsenic metabolism and endorphin receptors.Methods:A randomized, double-blind, placebo-controlled trial was conducted between January and March 2019 in Changde City, Hunan Province, China. Eligible patients with moderate to severe chronic pruritus under arsenic exposure were recruited, and randomly assigned to the naloxone group and the control group to receive sublingual naloxone and placebo (0.4 mg/d) respectively for 7 consecutive days. Outcomes were assessed before treatment and on day 7 after treatment, including the primary outcome (the dermatology life quality index [DLQI]) and secondary outcomes (depression symptoms, anxiety symptoms, and quality of sleep). Genotyping of the arsenic (+3 oxidation state) methyltransferase and 3 opioid receptor genes was performed using ligase detection reaction. Data analysis was performed using t test for normally distributed continuous variables, non-parametric tests for skewed continuous variables, and chi-square test for categorical data. Linear regression analysis was carried out to evaluate the effect of naloxone on outcome measures, while the interactive effect of demographic factors, genotypes and treatment methods on changes in DLQI were assessed by the generalized linear model. Results:A total of 126 patients with chronic arsenic exposure-related pruritus were enrolled, including 73 males and 53 females. They were randomly divided into the control group (64 cases) and the naloxone group (62 cases), with the ages being 60.0 ± 9.1 years and 58.4 ± 8.6 years, respectively. There were no significant differences between the two groups in terms of age, gender, income, education levels, or hair arsenic concentrations (all P > 0.05). After treatment, the decrease in DLQI scores was significantly higher in the naloxone group than in the control group (-8.79 ± 6.84 vs. -5.19 ± 8.10; P = 0.008). However, there were no significant changes in depression symptoms, anxiety symptoms, or quality of sleep between the naloxone group and control group (all P > 0.05). Linear regression analysis showed that naloxone significantly affected DLQI with a crude regression coefficient of -3.60 (95% CI: -6.25, -0.96; P = 0.008). Stratification analysis revealed that patients with the κ-opioid receptor gene rs1051660 (wild-type, CC) responded better to the treatment than those with the mutated genotype (CA), and there was a significant interaction between the rs1051660 genotype and therapeutic drugs in relation to DLQI changes ( P = 0.014) . Conclusion:Naloxone can effectively improve health-related quality of life in patients with chronic arsenic exposure-related pruritus, and its efficacy is modified by the gene polymorphism of the κ-opioid receptors.