Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Objective To identify the potential immune biomarkers of critical limb ischemia(CLI)in patients with diabetes.Methods From January 2018 to December 2023,102 patients who were definitely diagnosed as CLI and diabetes foot ulcers(DFU)requiring percutaneous transluminal angioplasty and foot surgery were enrolled.Serum levels of 18 cellular immune and inflammatory factors including soluble CD40 ligand(sCD40L),IFN-α,IFN-γ,IL-2,IL-4,IL-6,IL-8,IL-10,IL-13,IL-18,et cetera,were measured in these patients.Results The levels of circulating serum sICAM-1 and endothelin-1 showed a negative correlation with the recovery of DFU.Moreover,PAI-1 and endothelin-1 were related to the demand for neovascular reconstruction.The circulating serum levels of thrombomodulin and sCD40L were associated with new and recurrent lesions.Conclusion The level of circulating biomarkers related to the immunity of vascular endothelial cell can be used to predict the risk of new or recurrent CLI in patients with diabetes.

Objective:To investigate the relationship between partial activated thromboplastin time (APTT), lactate dehydrogenase-1 (LDH-1), neutrophil (NEU) and rhabdomyolysis (RM) -associated acute kidney injury (AKI) in exertional heat stroke (EHS) patients.Methods:The valid data of 261 EHS patients hospitalized in the General Hospital of the Southern Theater Command of the PLA from May 2008 to November 2019 were respectively included as the study objects, including 147 patients with RM. Basic data and peripheral blood indexes of the patients were collected, and the patients with RM were divided into non-AKI group and AKI group according to whether they had AKI. Binary Logistic regression was used to analyze the independent influencing factors of RM combined with AKI, and ROC curve was used to analyze the predictive value of relevant indicators on RM concurrent AKI.Results:Among 147 patients with RM, 57 (38.8%) had AKI. Using whether RM was combined with AKI as the dependent variable, variables showing statistical significance ( P<0.05) in univariate analysis were included as independent variables. Model 1 was established through binary logistic regression analysis, while Model 2 was derived using forward selection. The results of Model 2 revealed that NEU ( OR=1.196, 95% CI: 1.082-1.322, P<0.05), LDH-1 ( OR=1.015, 95% CI: 1.005-1.024, P<0.05), and APTT ( OR=1.013, 95% CI: 1.004-1.022, P<0.05) were independent risk factors for RM patients complicated with AKI ( all P<0.05). The AIC value for Model 1 was 166.914, while that for Model 2 was 150.276, indicating that Model 2 outperformed Model 1. The predictive value of NEU, LDH-1 combined with APTT for RM complicated by AKI: The area under the ROC curve (AUC) was 0.830 (95% CI: 0.764-0.897). When the critical value is ≥0.387, it indicates RM complicated by AKI, with a specificity of 0.719 and a sensitivity of 0.811. Conclusions:NEU, LDH-1 and APTT are closely related to AKI in RM, and the combined detection of NEU, LDH-1 and APTT is helpful for early diagnosis of AKI in RM.

Objective To explore the correlation between serum homocysteine(Hcy),25-hydroxyvitamin D[25(OH)D]and frailty with type 2 diabites mellitus(T2DM)complicated with sarcopenia.Methods From September 2021 to March 2023,210 elderly T2DM patients were selected from the Department of Geriatrics of The First People's Hospital of Yunnan Province,and divided into simple T2DM(n=99)group,mild sarcopenia(M-Sar,n=59)group and severe sarcopenia(S-Sar,n=52)group.The"Elderly Comprehensive Assessment System"was used to evaluate subjects.The influencing factors of T2DM complicated with sarcopenia were analyzed by Logistic regression.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of Hcy,25(OH)D combined with frailty in evaluating T2DM with sarcopenia.Results In T2DM,M-Sar and S-Sar groups,the age,Hcy,the risk rate of balance gait work falling and the rate of weakness increased in turn(P<0.05),while BMI,hemoglobin,25(OH)D,the rate of good nutrition,the normal rate of basic daily living,the low risk rate of falling,the rate of good balance gait function and the rate of no weakness decreased in turn(P<0.05).Logistic regression analysis showed that serum Hcy,frailty and 25(OH)D were the influencing factors of senile T2DM complicated with sarcopenia.Hcy,25(OH)D and frailty combined to predict T2DM with sarcopenia had an area under ROC carve of 0.815,with a sensitivity of 0.811 and a specificity of 0.717.Conclusions Serum Hcy,25(OH)D and frailty are closely related to T2DM combined with sarcopenia.Detection of Hcy and 25(OH)D combined with frailty score is helpful for early diagnosis of sarcopenia in primary hospitals.

Diabetic retinopathy(DR)is a kind of microvascular disease caused by the long-term influence of diabetes mellitus(DM),and it is one of the main cause of global visual impairment and blindness.Its typical characteristics include microaneurysms,hard exudates,macular edema(DME)and neovascularization.Its pathogenesis is diverse,and the root cause is oxidative stress and advanced glycosylation end products.The nuclear red blood cell related factor 2(Nrf2)signa-ling pathway plays an important role in preventing various diseases.As one of the characteristics of DM,hyperglycemia will activate the generation of reactive oxygen species(ROS)in mitochondria.These oxidative stress factors activate the nucle-ar transcription factor κB pathway,becoming the main inducement of various complications of DM.This pathway will in-duce increased transcription of proinflammatory cytokines,including tumor necrosis factor-alpha,transforming growth fac-tor-beta and interleukin-1.The active ingredients of traditional Chinese medicine have significant antioxidant,anti-inflam-matory,anti-apoptotic and angiogenesis-promoting effects,and can block the progression of DR through various mecha-nisms.In this article,the research status of traditional Chinese medicine targeting the Nrf2 signaling pathway in the preven-tion and treatment of DR is reviewed to guide clinical and scientific research.

Objective To identify the potential immune biomarkers of critical limb ischemia(CLI)in patients with diabetes.Methods From January 2018 to December 2023,102 patients who were definitely diagnosed as CLI and diabetes foot ulcers(DFU)requiring percutaneous transluminal angioplasty and foot surgery were enrolled.Serum levels of 18 cellular immune and inflammatory factors including soluble CD40 ligand(sCD40L),IFN-α,IFN-γ,IL-2,IL-4,IL-6,IL-8,IL-10,IL-13,IL-18,et cetera,were measured in these patients.Results The levels of circulating serum sICAM-1 and endothelin-1 showed a negative correlation with the recovery of DFU.Moreover,PAI-1 and endothelin-1 were related to the demand for neovascular reconstruction.The circulating serum levels of thrombomodulin and sCD40L were associated with new and recurrent lesions.Conclusion The level of circulating biomarkers related to the immunity of vascular endothelial cell can be used to predict the risk of new or recurrent CLI in patients with diabetes.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

This study aims to investigate the effects of astragalus polysaccharide (APS) on diabetic retinopathy through the SHH-Gli1-AQP1 pathway. The anti-type 2 diabetes mellitus (T2DM) targets of APS were identified through comprehensive searches of drug and disease-related databases. A protein-protein interaction network was then constructed, followed by GO and KEGG enrichment analyses.Molecular docking simulations were performed to evaluate the interactions of APS and metformin with Gli1 and AQP1. An in vivo T2DM rat model was established via streptozotocin (STZ) injection and treated with metformin and varying doses of APS for 12 weeks. Histological changes in retinal cells were assessed using H&E and PAS staining. The expression levels of AQP1, Gli1, and SHH in the retina were measured using immunohistochemistry, Western blotting, immunofluorescence, and ELISA. Additionally, mRNA expression of AQP1, Gli1, and SHH was quantified by RT-qPCR. Bioinformatic analyses indicated that Gli1 and AQP1, key components of the SHH-Gli1-AQP1 signaling pathway, may be associated with T2DM. Subsequent experiments demonstrated that the STZ-induced T2DM rats exhibited significant retinal damage, which was notably mitigated by both APS and metformin treatments. Furthermore, the SHH-Gli1-AQP1 signaling pathway was found to be overactivated in STZ-induced T2DM rats. Treatment with APS and metformin significantly reduced the elevated expression levels of SHH, Gli1, and AQP1. APS effectively inhibits retinal damage of STZinduced T2DM rats by restraining the SHH-Gli1-AQP1 signaling pathway.

This study aims to investigate the effects of astragalus polysaccharide (APS) on diabetic retinopathy through the SHH-Gli1-AQP1 pathway. The anti-type 2 diabetes mellitus (T2DM) targets of APS were identified through comprehensive searches of drug and disease-related databases. A protein-protein interaction network was then constructed, followed by GO and KEGG enrichment analyses.Molecular docking simulations were performed to evaluate the interactions of APS and metformin with Gli1 and AQP1. An in vivo T2DM rat model was established via streptozotocin (STZ) injection and treated with metformin and varying doses of APS for 12 weeks. Histological changes in retinal cells were assessed using H&E and PAS staining. The expression levels of AQP1, Gli1, and SHH in the retina were measured using immunohistochemistry, Western blotting, immunofluorescence, and ELISA. Additionally, mRNA expression of AQP1, Gli1, and SHH was quantified by RT-qPCR. Bioinformatic analyses indicated that Gli1 and AQP1, key components of the SHH-Gli1-AQP1 signaling pathway, may be associated with T2DM. Subsequent experiments demonstrated that the STZ-induced T2DM rats exhibited significant retinal damage, which was notably mitigated by both APS and metformin treatments. Furthermore, the SHH-Gli1-AQP1 signaling pathway was found to be overactivated in STZ-induced T2DM rats. Treatment with APS and metformin significantly reduced the elevated expression levels of SHH, Gli1, and AQP1. APS effectively inhibits retinal damage of STZinduced T2DM rats by restraining the SHH-Gli1-AQP1 signaling pathway.

Low-intensity pulsed ultrasound（LIPUS），with its remarkable advantages of higher safety and better penetrability，has gradually become a novel method of physical adjuvant therapy. Previous studies have verified that LIPUS can modulate the immune response of different immune cells such as macrophage，T lymphocyte，and neutrophil by reducing the level of pro-inflammatory cytokines. Therefore，it plays a crucial role on acceleration of fracture healing，expedition of wound repair，and repairation of myocardial injury. The review summarizes the regulatory effects and potential mechanisms of LIPUS on abnormal immune cell responses triggered by various diseases.