OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

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 clarify the biomechanical properties of oblique lumbar interbody fusion(OLIF)combined with lateral plate(LP)fixation under different bone conditions by means of finite element(FE)analysis,so as to provide mechanical basis for clinical practice.Methods The three-dimensional nonlinear L3_5 FE model of the spine was constructed.Different material properties were assigned to each part of the model to establish a model of normal bone(NB),osteopenia(OS)and osteoporosis(OP)of the lumbar spine.OLIF combined with the following three internal fixation models were established.For NB,there were OLIF alone(M0),OLIF+LP fixation(M1),and OLIF+bilateral pedicle screw(BPS)fixation(M2);for OS,there were OLIF alone(N0),OLIF+LP fixation(N1),and OLIF+BPS fixation(N2);for OP,there were OLIF alone(P0),OLIF+LP fixation(P1),and OLIF+BPS fixation(P2).A 500 N load was applied on the upper surface of L3 to represent the weight of the upper body,and a 7.5 N·m moment was used to simulate the vertebral motion under six different conditions:flexion(FL),extension(EX),left bending(LB),right bending(RB),left rotation(LR)and right rotation(RR).The range of motion(ROM)of the fixed segment of NB,OS and OP models was calculated,and the overall stress of the vertebral body,the stress of the cage and the internal fixation device were recorded.Results Compared with the complete model,the stability of each surgical model increased.Compared with M0,ROM of M1 decreased,especially in the LB and RB,which was roughly equivalent to the stability of BPS but weaker than BPS in the control FL and EX direction.The situation in OS and OP model was similar to that in NB.Under the same internal fixation,L4_5 ROM gradually increased with bone deterioration.The overall intervertebral ROM of N1 in the FL direction increased by 16.1％compared with M1,P1 in the FL direction increased by 32.1％compared with M1,and P1 in the FL direction increased by 19.0％compared with N1.With the increase of posterior internal fixation,the overall stress of vertebral body,Cage and internal fixation stress showed a downward trend.Under the same internal fixation,with the loss of bone mass,the overall stress of the model gradually increased.Compared with M0,P0 increased the most in LR,reaching 56.5％.In the NB and OS models,the peak stress of the LP fixation under FL exceeded the minimum yield strength of the material by 22.7％and 33.8％,respectively,and was less than the minimum fatigue strength and yield strength of the material under the rest of the motion.In the OP,the peak stress of the internal fixation exceeded the minimum fatigue strength of the material at FL and EX,and reached 53.3％(＞50％)at FL.Conclusions Under NB and OS,OLIF combined with LP fixation can significantly improve the stability of the surgical segment,especially in LB and RB directions,and the overall stability is weaker than that of BPS fixation.Under OP,FL and EX may increase the risk of internal fixation failure.Combination with BPS fixation should be considered to improve the safety of fixation.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:The aim of this study is to explore the correlation among serum hepcidin,ferritin,and q-Dioxn MRI with upgrading,upstaging and biochemical recurrence in prostate cancer(PCa)patients.Methods:A total of 103 PCa patients di-agnosed by biopsy were selected for this study.All patients underwent q-Dixon MRI prior to biopsy for T2*value measurement.Then serum hepcidin and ferritin were measured before receiving radical prostatectomy.Pathological grading and staging were conducted both preoperatively and postoperatively.The correlations among hepcidin,ferritin,T2*values,and postoperative upgrading,upstaging,biochemical recurrence were subsequently analyzed.Results:The hepcidin level of PCa patients was measured at(123.51±23.03)ng/mL,while the ferritin level was recorded at(239.80±79.59)ng/mL,and the T2* value was(41.07±6.37)ms.A total of 49 and 36 cases were observed with upgrading and upstaging in postoperative pathology,respectively.The median follow-up duration was 28.0 months(6.0-38.0 months),during which biochemical recurrence was observed in 12 cases.For upgrading,hep-cidin and ferritin demonstrated the predictive efficacy,with areas under the ROC curve of 0.777 and 0.642,respectively,whereas T2*values did not show sufficient predictive power.For upstaging,hepcidin,ferritin,and T2*exhibited predictive efficacy,with areas under the ROC curve of 0.806,0.696,and 0.655,respectively.Multivariate Logistic regression analysis indicated that hepcidin served as an independent risk factor for both upgrading(OR 1.055,95％CI 1.027-1.085,P＜0.001)and upstaging(OR 1.094,95％CI 1.040-1.152,P＜0.001).Cox regression analysis showed that hepcidin(95％CI 1.000-1.052,P=0.049)was a sig-nificant risk factor for predicting biochemical recurrence.Conclusion:Hepcidin could serve as a predictor for pathological upgra-ding,upstaging and biochemical recurrence after radical prostatectomy,which provides a novel potential index for risk stratification and prognostic evaluation of PCa patients.

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 clarify the biomechanical properties of oblique lumbar interbody fusion(OLIF)combined with lateral plate(LP)fixation under different bone conditions by means of finite element(FE)analysis,so as to provide mechanical basis for clinical practice.Methods The three-dimensional nonlinear L3_5 FE model of the spine was constructed.Different material properties were assigned to each part of the model to establish a model of normal bone(NB),osteopenia(OS)and osteoporosis(OP)of the lumbar spine.OLIF combined with the following three internal fixation models were established.For NB,there were OLIF alone(M0),OLIF+LP fixation(M1),and OLIF+bilateral pedicle screw(BPS)fixation(M2);for OS,there were OLIF alone(N0),OLIF+LP fixation(N1),and OLIF+BPS fixation(N2);for OP,there were OLIF alone(P0),OLIF+LP fixation(P1),and OLIF+BPS fixation(P2).A 500 N load was applied on the upper surface of L3 to represent the weight of the upper body,and a 7.5 N·m moment was used to simulate the vertebral motion under six different conditions:flexion(FL),extension(EX),left bending(LB),right bending(RB),left rotation(LR)and right rotation(RR).The range of motion(ROM)of the fixed segment of NB,OS and OP models was calculated,and the overall stress of the vertebral body,the stress of the cage and the internal fixation device were recorded.Results Compared with the complete model,the stability of each surgical model increased.Compared with M0,ROM of M1 decreased,especially in the LB and RB,which was roughly equivalent to the stability of BPS but weaker than BPS in the control FL and EX direction.The situation in OS and OP model was similar to that in NB.Under the same internal fixation,L4_5 ROM gradually increased with bone deterioration.The overall intervertebral ROM of N1 in the FL direction increased by 16.1％compared with M1,P1 in the FL direction increased by 32.1％compared with M1,and P1 in the FL direction increased by 19.0％compared with N1.With the increase of posterior internal fixation,the overall stress of vertebral body,Cage and internal fixation stress showed a downward trend.Under the same internal fixation,with the loss of bone mass,the overall stress of the model gradually increased.Compared with M0,P0 increased the most in LR,reaching 56.5％.In the NB and OS models,the peak stress of the LP fixation under FL exceeded the minimum yield strength of the material by 22.7％and 33.8％,respectively,and was less than the minimum fatigue strength and yield strength of the material under the rest of the motion.In the OP,the peak stress of the internal fixation exceeded the minimum fatigue strength of the material at FL and EX,and reached 53.3％(＞50％)at FL.Conclusions Under NB and OS,OLIF combined with LP fixation can significantly improve the stability of the surgical segment,especially in LB and RB directions,and the overall stability is weaker than that of BPS fixation.Under OP,FL and EX may increase the risk of internal fixation failure.Combination with BPS fixation should be considered to improve the safety of fixation.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.