Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

The plasma membrane (PM) plays an essential role in maintaining cell homeostasis, therefore, timely and effective repair of damage caused by factors such as mechanical rupture, pore-forming toxins, or pore-forming proteins is crucial for cell survival. PM damage induces membrane rupture and stimulates an immune response. However, damage resulting from regulated cell death processes, including pyroptosis, ferroptosis, and necroptosis, cannot be repaired by simple sealing mechanisms and thus, requires specialized repair machinery. Recent research has identified a PM repair mechanism of regulated cell death-related injury, mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. Here, we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury, with particular focus on processes related to regulated cell death. This overview, along with continued research in this field, may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.

Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

Objective: To investigate the status of drug resistance before anti-retroviral therapy among newly dignosed HIV/AIDS patients aged ≥50 years in Yangzhou City, Jiangsu Province, so as to provide the evidence for improving the anti-retroviral therapy effect of AIDS. Methods: HIV/AIDS patients aged ≥50 years who were newly dignosed in Yangzhou City from 2021 to 2024 and did not receive anti-retroviral therapy were selected. Basic information were collected through the Chinese Disease Prevention and Control Information System. Blood samples were collected to determine CD4+T lymphocyte (CD4 cell) counts and HIV-1 viral load. Following nucleic acid extraction, the pol gene region was amplified using reverse transcription and nested PCR, and subsequently subjected to Sanger sequencing. The resulting sequences were uploaded to the Stanford University HIV Drug Resistance Database to analyze drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and nucleoside reverse transcriptase inhibitors (NRTIs). Results: Totally 404 blood samples from HIV/AIDS patients were collected, with successful sequencing of the pol gene region in 341 cases. Among them, 253 (74.19%) were males and 88 (25.81%) were females, with a mean age of (62.48±7.60) years. A total of 152 cases (44.57%) had CD4 cell counts below 200 cells/μL, and 296 cases (86.80%) had HIV-1 viral loads exceeding 5 000 copies/mL. A total of 87 cases exhibited drug resistance-associated mutations, corresponding to a mutation rate of 25.51%. The predominant mutation site was V179, with a mutation rate of 17.01%. A total of 29 cases exhibited resistance to at least one drug, resulting in a resistance rate of 8.50%. The resistance rates to NNRTIs, PIs, and NRTIs were 5.57%, 2.93%, and 1.17%, respectively. The HIV/AIDS patients exhibited varying degrees of resistance to 13 anti-retroviral drugs, with low- or intermediate-level drug resistance being predominant. High-level drug resistance cases were observed against NNRTIs such as nevirapine and efavirenz. Conclusions The drug resistance rate before anti-retroviral therapy among newly dignosed HIV/AIDS patients aged ≥50 years in Yangzhou City was at a moderate level. The predominant resistance mutation was observed at V179 site, with NNRTIs resistance being most prevalent, primarily demonstrating low- or intermediate-level drug resistance.

Objective: To establish a nomogram prediction model for Alzheimer's disease (AD) among the elderly in community, so as to provide the evidence for early screening and prevention of AD. Methods: Based on the Zhejiang Healthy Aging Cohort Study, the elderly aged 60-90 years who completed the baseline survey were selected as the study subjects. Follow-up surveys were conducted from 2015 to 2016 and from 2019 to 2021. Sociodemographic characteristics, lifestyle factors, medical history, and waist circumference were collected through questionnaire surveys and physical examinations. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a diagnosis of AD was made based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale and medical history. The participants were randomly divided into training and validation sets at 8∶2 ratio. LASSO regression was used to screen for predictive factors. Multivariable logistic regression model was used to analyze predictive factors and construct a nomogram. The model was analyzed and evaluated using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 6 988 elderly were included at baseline, with a mean age of (68.19±6.63) years. There were 3 438 males (49.20%), and 3 550 females (50.80%). The median follow-up duration was 4.90 (interquartile range, 3.80) years, with 817 new cases of AD were identified, yielding an incidence of 11.69%. LASSO regression and multivariable logistic regression showed that age (OR=1.017, 95%CI: 1.005-1.030), gender (female, OR=1.820, 95%CI: 1.533-2.165), educational level (primary school, OR=0.813, 95%CI: 0.673-0.980), physical exercise (not active, OR=1.572, 95%CI: 1.260-1.980), dining companions (spouse and children, OR=0.771, 95%CI: 0.598-0.995), baseline MMSE score (OR=0.843, 95%CI: 0.821-0.866), and waist circumference (OR=0.981, 95%CI: 0.973-0.989) were risk predictors for AD among the elderly in community. The prediction model demonstrated an area under the ROC curve of 0.740 (95%CI: 0.698-0.783) in the validation set, with a sensitivity of 0.731 and a specificity of 0.667. DCA indicated that when the probability threshold was 0.060 to 0.325, the clinical net benefit was relatively high. Conclusion The AD risk prediction model constructed in this study has good discrimination and clinical practicability, can be used for early screening of AD among the elderly in the community.

Small intestinal bacterial overgrowth（SIBO）is a clinically common but poorly recognized disease with clinical symptoms that overlap with those of functional gastrointestinal disorders（FGID）. FGID is a common risk factor for the occurrence of SIBO，and its SIBO incidence rate is significantly higher than that of healthy people，and has a certain correlation. Intestinal microbiota dysbiosis（including SIBO）plays an important role in the pathophysiology of FGID. At present，the diagnosis and treatment of SIBO still face challenges，and the treatment plan of FGID is gradually introduced into the treatment of SIBO. SIBO and FGID are closely related in clinical manifestations，incidence rate，pathophysiology，treatment and other aspects，but there is little research on the relationship between them. Prospective and large-scale clinical research is still needed to improve understanding and diagnostic accuracy.This article reviews the research progress on the relationship between SIBO and FGID.

Objective To investigate the relationship between serum levels of interferon-inducible protein 10(IP-10)and S100 calcium-binding protein A8(S100A8)and the prognosis of patients with severe pneumo-nia(SP).Methods A total of 315 SP patients admitted to the hospital from January 2021 to December 2023 were selected as the SP group,and 315 non-SP patients admitted to the hospital during the same period were selected as the non-SP group.According to the prognosis of SP patients 28 d after admission,they were divided into good prognosis group(199 cases)and poor prognosis group(116 cases).Enzyme-linked immunosorbent assay was used to detect serum IP-10 and S100A8 levels in SP patients.Pearson correlation analysis was used to analyze the correlation between IP-10,S100A8 levels and infection indicators[high-sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),interleukin-6(IL-6)].Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in SP patients.Receiver operating characteristic(ROC)curve was used to analyze the value of hs-CRP,PCT,IP-10 and S100A8 levels in predicting the poor prognosis of SP patients.Results The serum levels of IP-10,S100A8,hs-CRP,PCT and IL-6 in SP group were higher than those in non-SP group(P＜0.05).Paerson correlation analysis showed that serum IP-10 level in SP group was positively correlated with hs-CRP,PCT and IL-6(r=0.744,0.757,0.740,P＜0.05).S100A8 level was posi-tively correlated with hs-CRP,PCT and IL-6(r=0.769,0.718,0.744,P＜0.05).There were significant differences in oxygenation index,acute physiology and chronic health evaluation Ⅱ score,clinical pulmonary in-fection score and levels of hs-CRP,PCT,IP-10 and S100A8 between the poor prognosis group and the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that hs-CRP,PCT,IP-10 and S100A8 were risk factors for poor prognosis in SP patients,and oxygenation index was a protective factor(P＜0.05).The ROC curve showed that the area under curve(AUC)of the combination of hs-CRP,PCT,IP-10 and S100A8 in predicting poor prognosis of SP patients was 0.965,which was greater than the AUC of the four alone(Zhs-CRP=4.009,ZPCT=4.022,ZIP-10=3.696,ZS100A8=3.309,P＜0.05).Conclusion The serum lev-els of IP-10 and S100A8 are up-regulated in SP patients.The combination of IP-10 and S100A8 has a high pre-dictive value for poor prognosis in SP patients.

Objective:To investigate the role and potential regulation mechanism of miR-22-3p in lipotoxic hepatocyte inflam-matory injury and apoptosis caused by palmitic acid(PA).Methods:Human normal immortalized hepatocytes(LO2 cells)were treated with different concentrations of PA for 24 h.CCK-8 and qRT-PCR were used to detect cell proliferation and miR-22-3p expression.miR-22-3p mimics or inhibitors were transfected into LO2 cells and then treated with 0.32 mmol/L PA for 24 h,the expression level of miR-22-3p was determined by qRT-PCR;cell viability was determined by CCK-8;biochemical kits to determine the ALT and AST contents;the mRNA and protein expression levels of inflammatory cytokines TNF-α,IL-1β and IL-6 in intracellular and culture super-natants were determined by qRT-PCR and ELISA;the cell apoptosis rate in each group was determined by flow cytometry;the expres-sion levels of NF-κB signaling pathway-related proteins were detected by Western blot and immunofluorescence.Results:With the increaseing of PA concentration,the cell survival rate and the expression of miR-22-3p decreased in a dose-dependent manner.After PA treatment,the cell proliferation activity decreased significantly,the activities of ALT and AST enzymes were increased,the expressions of inflammatory cytokines TNF-α,IL-1β and IL-6 were increased,cell apoptosis was increased,and NF-κB signaling pathway was activated.Transfection of miR-22-3p mimics significantly increased the proliferation activity of LO2 cells,and decreased the levels of ATL,AST,TNF-α,IL-1β,IL-6 and apoptosis,and inhibited the activation of NF-κB signaling pathway.Transfection of miR-22-3p inhibitor further activated NF-κB signaling pathway,and promoted cell inflammatory injury and apoptosis(all P<0.05).Conclusion:Overexpression of miR-22-3p can alleviate PA-induced apoptosis and inflammation,and the mechanism is related to inhibit the activation of NF-κB signaling pathway.

Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.