Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the regulatory effect and mechanism of disidin domain receptor 1(DDR1)on the proliferation and apoptosis of glioma cells.Methods The expression levels of DDR1 in human glioma cells and normal glial cells were detected by qRT-PCR and Western blot.Glioma cells U251 with stable overexpression and knockdown of DDR1 were constructed by lentivirus infection,the proliferation ability of the stable cell line was detected by CCK-8 assay,and the apoptosis ability was detected by flow cytometry.Western blot was used to detect the activation of related pathways in stable cell lines and explore the regulatory mechanism of DDR1.Results The results of qRT-PCR and Western blot showed that the expression level of DDR1 in human glioma cell U251 was higher than those in human glioma cell U87 and normal glial cell HEB.Therefore,the U251 cell line was selected for subsequent experiments.CCK-8 assay showed that overexpression of DDR1 promote the proliferation of glioma cells,while knockdown of DDR1 inhibit the proliferation of glioma cells.The results of flow cytometry showed that overexpression of DDR1 inhibit the apoptosis of glioma cells,while knockdown of DDR1 induce the apoptosis of glioma cells.Western blot results showed that overexpression of DDR1 activate the PI3K/AKT pathway,while knockdown of DDR1 inhibit the activation of the PI3K/AKT pathway.Conclusion DDR1 can enhance the proliferation ability of glioma cells and inhibit their apoptosis by activating the PI3K/AKT pathway,promoting the development of glioma cells.Therefore,DDR1 may become a potential target for the treatment of glioma.

The 97th Annual Meeting of the Japanese Gastric Cancer Association was held from March 12 to March 14,2025,in Nagoya,Japan.The conference was chaired by Professor Kazuhiro Uyama from Fujita Medical University and attracted nearly 2 000 scholars from around the world,including Japan,China,the republic of Korea,the United States,and Europe.With the theme of"Digital Innovation in Gastric Tumors,"the conference focused on the application of artificial intelligence,robotic surgery,and other innovations in the treatment of gastric cancer.It explored how high-precision and highly reproducible robotic surgical techniques are transforming traditional approaches to gastric cancer surgery,along with topics such as digital innovation,future medical policies,and strategies that herald a new era in healthcare.The meeting featured one main venue and 60 sub-venues with different themes,ultimately accepting 1 003 submissions.A total of 158 oral presentations covering 80 topics and 203 poster presentations were delivered.Among them,approximately 145 lectures were related to robotic surgery for gastric cancer,and when including poster presentations,nearly 255 topics were associated with gastric cancer robotic surgery.Additionally,the 7th edition of the Japanese Gastric Cancer Treatment Guidelines was released during the meeting.Our team had the honor of participating in this prestigious event.Drawing from our experience at both this conference and the 17th Annual Meeting of the Japanese Society for Robotic Surgery held in Utsunomiya,Japan,from March 7 to March 8,2025,we provide a detailed report on the latest advancements in robotic surgery for gastric cancer,hoping to offer valuable insights and references for fellow surgeons both in China and abroad.

The development of breast cancer is closely related to the information transfer in its microenvironment.As a novel information communication tool,exosomes present non-coding RNAs that are involved in breast cancer cell proliferation,migration,invasion,tumour-associated fibroblasts ogenesis,cell cycle,degradation of oncogenes,etc.This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.

Objective:To explore the application effects of improved case-based learning (CBL) combined with hierarchical and progressive teaching in the standardized training of nuclear medicine resident physicians.Methods:A total of 43 resident physicians who rotated in the nuclear medicine base of our hospital between 2018 and 2023 were selected as the research subjects and divided into an experimental group ( n=22) and a control group ( n=21) according to the order of enrollment. The control group received the traditional teacher-centered teaching model and was divided into junior and senior subgroups according to the training years. The experimental group received the improved CBL combined with hierarchical and progressive teaching. First, through multidimensional evaluation (theoretical testing + standardized case analysis), the students were scientifically divided into preliminary, intermediate, and advanced levels. Subsequently, progressive teaching objectives were set for different levels, and real clinical cases embedded with hierarchical learning tasks were published. During the teaching process, a dynamic discussion mode combining homogeneous and heterogeneous grouping was adopted, and personalized guidance was provided by the teachers. Finally, dynamic hierarchical adjustment was implemented through process evaluation. After the training, the two groups were compared in terms of exit assessment performance (including professional basic theory and practical skills) and teaching satisfaction. Results:The total score of the exit assessment of the experimental group was higher than that of the control group [(86.90±6.78) vs. (75.09±8.45)], and the difference was statistically significant. In terms of practical skill assessment, the experimental group scored higher than the control group in modules such as imaging symptom description [(22.34±2.56) vs. (19.85±3.12)], localization diagnosis [(23.01±2.11) vs. (20.12±2.98)], qualitative diagnosis [(22.89±2.67 vs. 18.67±3.45)], and differential diagnosis [(21.56±2.89) vs. (17.23±3.78)] ( P<0.01). The teaching satisfaction survey showed that the satisfaction scores of the experimental group were higher than those of the control group in nine domains, including theoretical knowledge mastery, clinical thinking, image interpretation, and learning initiative ( P<0.05). Conclusions:The improved CBL combined with hierarchical and progressive teaching can effectively improve the exit assessment performance, clinical practice skills, and teaching satisfaction of nuclear medicine resident trainees, and is worthy of promotion.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.