Diabetic nephropathy （DN） is one of the most common and severe microvascular complications of diabetes， with a complex pathogenesis involving immune inflammatory responses， oxidative stress， apoptosis， glomerulosclerosis， renal interstitial fibrosis， and other pathological processes. In recent years， numerous animal or cell model experiments have revealed that the transforming growth factor-β （TGF-β）/mothers against decapentaplegic homolog （Smad）， phosphoinositide 3-kinase （PI3K）/ protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， mitogen-activated protein kinase （MAPK）， AMP-activated protein kinase （AMPK）， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2）， secretory glycoprotein （Wnt）/β-catenin， and other classical signaling pathways play important roles in the occurrence and development of DN. Traditional Chinese medicines， as natural drugs， possess characteristics such as multiple components， multiple targets， and few adverse reactions， demonstrating unique advantages in regulating the aforementioned signaling pathways and improving renal pathological changes. This review summarized recent research progress on the intervention of DN through the regulation of the aforementioned signaling pathways by single compounds and formulas of traditional Chinese medicine， focusing on their mechanisms of action in regulating immune inflammatory responses， inhibiting renal fibrosis， oxidative stress， improving metabolic disorders， and other aspects. The aim is to provide theoretical references for a deeper understanding of the modern pharmacological basis and clinical application of traditional Chinese medicine in the treatment of DN.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

ObjectiveTo improve the quality and service performance of community visual health services in Shanghai, and to establish a set of reasonable and effective evaluation index system for community visual health services. MethodsCentered on the national and Shanghai-based visual health policies and based on the current status and development trends of community visual health service program in Shanghai, the candidate indicators were formed through literature review and expert interviews, firstly. The framework of an evaluation index system was formulated through qualitative research successively, which was further revised and perfected using the Delphi method. Coefficient weights were calculated using the analytic hierarchy process (AHP), culminating in the establishment of the community visual health evaluation index system, lastly. ResultsA total of 22 visual health experts from district-level center for disease control, hospital ophthalmology and leaders in charging of visual health service in community health centers participated in the Delphi questionnaire survey, with a questionnaire recovery rate of 100% and an expert authority coefficient of 0.86, indicating high credibility. After a round of correspondence to experts’ importance ratings and discussions, a comprehensive evaluation index system comprising 3 primary indicators, 12 secondary indicators, and 47 tertiary indicators, along with 5 additional indicators, was finalized. ConclusionAn index system tailored to effective evaluation for community visual health initiatives was drawn up in this study, which can promote the capacity building in community eye health services, facilitating the high-quality development of visual health courses, and enhancing residents’ eye health.

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

OBJECTIVE: To assess the impact of albumin (Alb) administration on the prognosis of patients with acute kidney injury (AKI). METHODS: Clinical data of AKI patients in the intensive care unit (ICU) were retrospectively analyzed from the American Medical Information Mart of Intensive Care-IV (MIMIC-IV), including demographic data, acute physiology score (APS), comorbidities, vital signs, laboratory indicators, treatment status, ICU length of stay, and outcome indicators. The main outcome measure is ICU mortality. AKI patients were divided into Alb infusion group and Alb non infusion group based on whether they received Alb treatment. Multiple imputation was used to process missing data and eliminate variables that missing more than 30%. To ensure the stability of the results, propensity score matching (PSM) and inverse probability weighting (IPW) were used to correct the results. Using Kaplan-Meier survival curve and Cox proportional hazards regression model to evaluate the effect of Alb infusion on ICU survival rate in AKI patients. Perform subgroup analysis based on patient age, gender, and comorbidities to evaluate the prognostic effects of Alb on different patient subgroups. RESULTS: A total of 6 390 AKI patients were included, including 1 721 in the Alb infusion group and 4 669 in the Alb non infusion group. After adjusting for key covariates in the Cox regression model, compared with the Alb non infusion group, patients in the Alb infusion group were significantly younger in age, with APS III score, proportion of vasoactive drugs and continuous renal replacement therapy (CRRT) use, sepsis proportion, heart rate, respiratory frequency, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr), lactic acid (Lac), and arterial partial pressure of carbon dioxide (PaCO₂) levels significantly higher. The proportion of hypertension, myocardial infarction, and congestive heart failure, as well as blood pressure, urine output, platelet count (PLT), and Alb levels were significantly lower. The results of univariate and multivariate Cox regression analysis on the raw data showed that the risk of death in the Alb infusion group was significantly lower than that in the Alb non infusion group [hazard ratio (HR) = 0.69, 95% confidence interval (95%CI) was 0.60-0.80, all P < 0.05]. The results after propensity score matching (PSM) and inverse probability weighting (IPW) processing are consistent with the original data trend (both P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate during ICU stay in the Alb infusion group was significantly higher than that in the Alb non infusion group (24.48% vs. 12.17%, Log-Rank test: χ² = 74.26, P < 0.05). Subgroup analysis shows that Alb infusion has a more significant survival benefit for AKI patients who use vasoactive drugs, have concurrent sepsis, and do not have liver disease. CONCLUSION Albumin infusion can decrease the ICU mortality of AKI patients.
Humans ; Retrospective Studies ; Acute Kidney Injury/mortality* ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units ; Albumins/therapeutic use* ; Proportional Hazards Models ; Adult ; Databases, Factual

Objective To evaluate the efficacy and safety of percutaneous vertebroplasty(PVP)using a 17 G puncture needle for the treatment of painful cervical osteolytic metastases.Methods The clinical data of 42 patients with cervical osteolytic metastases(53 lesions in total),who were treated with PVP at the Affiliated Zhongda Hospital of Southeast University of China from March 2012 to March 2024,were retrospectively analyzed.Visual Analog Scale(VAS)was used to evaluate the clinical efficacy and procedure-related complications at one week,one month,3 months,6 months,and one year after PVP.Follow-up CT scan was performed at 1-3 days after PVP so as to evaluate the condition of bone cement filling and leakage.Results Successful PVP using a 17 G puncture needle was accomplished for all the 53 diseased cervical vertebrae.Among them,one patient had one diseased vertebra of C1 and each in 5 patients had one diseased vertebra of C2,and all the 6 lesions were treated with CT-guided PVP;each in 6 patients had one diseased vertebra of C2 and 30 patients had 41 diseased vertebrae of C3-C6,and all the 47 lesions were treated with DSA fluoroscopy-guided PVP.The mean volume of bone cement injected in each vertebra was(1.9±0.45)mL,and the mean bone cement filling rate in each vertebra was(83.5±9.7)％.The preoperative average VAS score was 8.2 points,and it decreased by 5.6,6.1,6.2,5.9,and 5.7 points at one week,one month,3 months,6 months,and one year after PVP,respectively.There was a statistically significant difference in VAS score between one week after PVP and before PVP(P＜0.01),but no statistically significant differences in VAS scores existed within one year after PVP(all P＞0.05).Asymptomatic leakage of bone cement occurred in 14(26.4％)cervical vertebrae.One patient developed pharyngeal infection(adopting the anterior oblique puncture approach),which was cured after anti-infection treatment.No procedure-related complications such as neck bleeding,hematoma,etc.were observed.The lesion control rates at 3,6,and 12 months after PVP were 94.3％,93.9％,and 88.9％,respectively,there was no statistically significant difference in lesion control rates among the follow-up time-points(P=0.580).Conclusion For the treatment of painful cervical osteolytic metastases,PVP using a 17 G puncture needle is clinically safe and feasible.PVP can quickly relieve cervical pain and maintain cervical stability for a long time.Bone cement filling has a good control effect on cervical osteolytic metastatic tumors,although this control effect will decrease over time.

Objective:To investigate the prognostic value of the combined use of central venous-arterial carbon dioxide partial pressure difference/arterial-central venous oxygen content difference ratio (Pv-aCO 2/Ca-vO 2) combined with peripheral perfusion index (PI) for prognosis in middle-aged and elderly patients with acute heart failure (AHF) complicated by hypoperfusion. Methods:A case-control study was conducted, enrolling middle-aged and elderly AHF patients with tissue hypoperfusion admitted to the Emergency Intensive Care Unit of Nanjing First Hospital from May 2022 to May 2024. The primary endpoint was 28-day all-cause mortality. Patients were divided into survival and death groups based on prognosis. Baseline characteristics and clinical data were compared between groups. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of risk factors. Stratified analysis based on optimal cutoff values was performed, and Kaplan-Meier survival curves were used to compare prognostic differences between subgroups.Results:A total of 70 patients with AHF and hypoperfusion were enrolled, with 36 deaths (28-day mortality rate: 51.43%). No significant differences were observed in baseline characteristics, N-terminal B-type natriuretic peptide precursor, creatine kinase, creatine kinase-myocardial band, cardiac troponin I,central venous pressure, or left ventricular ejection fraction between groups(all P>0.05). Compared with the survival group, the death group exhibited significantly higher APACHEⅡ scores, lactate levels, and Pv-aCO 2/Ca-vO 2 ratios, along with lower PI values (all P<0.05). The area under the ROC curve (AUCs) for PI, Pv-aCO 2/Ca-vO 2, and their combination in predicting 28-day mortality were 0.804 (95% CI: 0.701-0.908), 0.848 (95% CI: 0.758-0.938), and 0.922 (95% CI: 0.859-0.985), respectively. The optimal cutoff value for PI was 1.17 (sensitivity 83.3% and specificity 67.6%), and for Pv-aCO 2/Ca-vO 2 was 1.59 (sensitivity 77.8% and specificity 79.4%). Stratified analysis revealed that the PI≤1.17 group had a significantly higher 28-day mortality rate than the PI>1.17 group ( P<0.01), and the Pv-aCO 2/Ca-vO 2>1.59 group had a markedly higher mortality rate than the Pv-aCO 2/Ca-vO 2≤1.59 group ( P<0.01) ,consistent with Kaplan-Meier survival analysis. Conclusion:Early assessment of Pv-aCO 2/Ca-vO 2 combined with PI demonstrates superior predictive performance for prognosis in AHF patients with hypoperfusion.

Osteoporosis(OP)is a prevalent metabolic bone disease with a complex pathogenesis that has not yet been fully elucidated.Recent studies have revealed that the Toll-like receptor 4(TLR4)signaling pathway plays a significant role in the development and progression of OP.TLR4,a crucial immune receptor primarily expressed in immune cells,is involved in inflammatory responses and immune regulation.The TLR4 signaling pathway influences bone metabolism and remodeling through multiple mechanisms.Therefore,investi-gating the role of the TLR4 signaling pathway in OP is of great significance for its prevention and treatment.Re-search targeting the TLR4 signaling pathway provides novel insights and approaches for OP therapy.Future studies should further explore the mechanisms of the TLR4 signaling pathway,develop therapeutic agents that modulate this pathway,and validate their efficacy in OP through clinical trials,thereby offering more options for the clinical management of OP.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.