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.

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.

Objective To investigate the prevalence of common diseases among primary and secondary school students in Yichang City from 2019 to 2022, and to provide a scientific basis for formulating effective intervention measures in the future. Methods By random cluster sampling , 7 schools in urban areas and 5 schools in suburban counties were selected to screen common diseases such as myopia, dental caries, obesity and abnormal spinal curvature. Descriptive epidemiological methods were employed for statistical analysis. Results A total of 17 023 primary and secondary school students were screened from 2019 to 2022. The overall detection rate of common diseases from high to low was myopia (54.12%), caries (36.75%), overweight (15.17%), obesity (11.88%), malnutrition (5.80%), and abnormal spinal curvature (3.49%). The detection rates of myopia and abnormal curvature of the spine showed an increasing trend with years and school stages, while the detection rates of malnutrition and dental caries showed a decreasing trend with years and school stages. The detection rates of overweight and obesity showed no trend difference with years, and the detection rates of obesity showed a decreasing trend with school stages. The rates of myopia, overweight and obesity were higher in urban areas than those in suburban counties, and the rate of dental caries was higher in suburban counties than that in urban areas. The prevalence of overweight, obesity, and malnutrition in boys was higher than that in girls. The prevalence of myopia and dental caries in girls was higher than that in boys. The above differences were statistically significant (all P<0.05). Conclusion Myopia, dental caries, obesity, and abnormal curvature of the spine are the current focus of the prevention and treatment of common diseases in students. There are great differences between different regions, school stages, and genders. The ^“tripartite linkage^” of schools, families, and communities should be achieved with the joint efforts of the education and health departments to actively take targeted intervention measures to reduce the prevalence.

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 analyze the characteristics of 57 acquired immune deficiency syndrome(AIDS)patients complicated with cryptococcal meningitis and observe the treatment outcomes.METHODS Totally 57 AIDS pa-tients with complicated cryptococcal meningitis who were treated in Guiyang Public Health Treatment Center from Jan.2019 to Jun.2023 were continuously assigned as the cryptococcal meningitis group,meanwhile,57 patients with simple AIDS were chosen as the simple AIDS group based on a 1∶1 ratio matching case-control study.Both groups received standardized therapies on basis of the criteria.The clinical characteristics,T lymphocyte subsets,biochemical indexes and treatment outcomes were observed and compared between the two groups.RESULTS There were no significant differences in gastrointestinal reactions,fever and eye discomfort between the two groups;the incidence of neurological symptoms of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There was significant difference in the peripheral blood T lymphocyte subsets be-tween the cryptococcal meningitis group and the simple AIDS group(P＜0.05).The levels of whole blood CD4+,CD4+/CD8+and CD8+of the cryptococcal meningitis group were lower than those of the simple AIDS group;the serum glucose(GLU)level of the cryptococcal meningitis group was lower than that of the simple AIDS group;the serum adenosine deaminase(ADA)level of the cryptococcal meningitis group was higher than that of the sim-ple AIDS group;the serum immunoglobulin A(IgA)level of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There were no significant differences in the immunological failure,vir-ological failure and immunological failure plus virological failure between the two groups after the treatment for 6 months.CONCLUSIONS The incidence of neurological symptoms is higher among the patients with AIDS com-plicated with cryptococcal meningitis than among the patients with simple AIDS.The patients have poor treatment outcomes and more severe damage of T lymphocyte subset functions,and the levels of biochemical indexes vary a-mong the patients,which may provide bases for diagnosis of diseases and assessment of curative effect and prog-nosis.

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

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.

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 retrieve,evaluate and summarise the best evidence on screening and management of psychological distress in patients who had ostomy for colorectal cancer.Methods Literatures on psychological distress screening and management in patients undergoing colorectal cancer ostomy were systematically searched across various websites and databases of home and abroad from inception to 20th June,2024 including Cochrane Library,PubMed,Embase,CINAHL,Web of Science,CNKI,Wangfang,VIP,UpToDate,National Guideline Clearing-house,National Comprehensive Cancer Network,the National Institute for Health and Care Excellence,Scottish Intercollegiate Guidelines Network,the International Guideline Collaboration Network,Wound,Ostomy and Continence Nurses Society,World Council of Enterostomal Therapists,Medlive,Chinese Nursing Association.The search aimed to identify evidence on psychological distress screening and management in patients with colorectal cancer and stomas,including guidelines,evidence summaries,expert consensuses,systematic reviews,and Meta-analyses.The search was limited to articles published from the inception of each database to 20th June,2024.The searched literature included guidelines,evidence summary,expert consensus,systematic review,meta-analysis,etc..Two researchers independently evaluated the quality of literature and extracted evidences,as well as checked and integrated the evidences together with a panel of evidence-based research experts.Results A total of 14 articles were included,comprising four guidelines,one expert consensus,two evidence summaries,four meta-analyses and three systematic reviews.The articles encompassed 7 dimensions with a total of 18 pieces of evidence,including one in screening timing,one in screening tools,3 in screening content,3 in drug intervention,3 in self-management,5 in psychological support and 2 in health education.Conclusion The evidence summarised in this study on the screening and management of psychological distress in patients who had ostomy for colorectal cancer is scientifically comprehensive.It provides an evidence-based basis for medical staff in prevention and management of psychological distress in patients.It is necessary to formulate a scientific management plan in clinical practice,according to the specific requirements of departments,the patients and their family members.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.