Diabetic kidney disease （DKD）， a common complication of diabetes mellitus， is a leading global cause of end-stage renal disease （ESRD）. Current therapeutic strategies primarily focus on symptomatic management but exhibit limited efficacy in halting disease progression to ESRD， and some drugs carry non-negligible toxic side effects. Traditional Chinese medicine （TCM） has a long history in treating DKD， with single TCM and TCM compounds demonstrating unique advantages in multi-target， multi-pathway， and multi-effect therapeutic interventions. Tripterygium wilfordii （TW）， known for its effects in promoting blood circulation， dredging collaterals， dispelling wind， removing dampness， reducing swelling， and alleviating pain， contains bioactive components such as Tripterygium glycosides （TWG）， triptolide （TPL）， tripdiolide （TPD）， and celastrol （CEL）. The active ingredients possess various functions， including regulating immune-inflammatory balance， ameliorating renal fibrosis and glomerulosclerosis， combating oxidative stress， protecting podocytes， and improving glucose and lipid metabolism， all of which play a significant role in the treatment of DKD. This review summarized the mechanisms underlying the therapeutic effects of T. wilfordii and its active ingredients on DKD， aiming to provide insights for clinical management and novel drug development of DKD.

BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

Immunoglobulin A nephropathy （IgAN） is a common primary glomerular disease and a frequent cause of chronic renal failure. Tripterygium wilfordii is a traditional Chinese herbal medicine， which possesses the effects of promoting blood circulation， relieving swelling and pain， and dispelling wind and dampness. Modern pharmacological studies have shown that T. wilfordii multiglucoside exhibit anti-inflammatory and immunomodulatory effects， inhibit mesangial cell proliferation， protect podocytes， ameliorate endothelial cell injury， and regulate gut microbiota disturbances. Triptolide also possesses anti-inflammatory and immunomodulatory properties， suppresses mesangial cell proliferation， and protects podocytes. Celastrol demonstrates anti- inflammatory and immunomodulatory functions as well as the ability to improve endothelial cell damage. Through these mechanisms， T. wilfordii and its active components can play a role in alleviating clinical symptoms and delaying disease progression in the treatment of IgAN. Future research should focus on in-depth analysis and mechanistic investigation of these active ingredients， promote high-quality clinical studies， systematically evaluate the synergistic effects among them， and emphasize strategies for reducing toxicity and enhancing efficacy， thereby providing more comprehensive and reliable evidence-based foundations for the clinical treatment of IgAN.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Objective To investigate the expression levels of serum miR-186-5p and miR-942-5p in patients with glioma and their clinical significance.Methods A total of 98 patients with glioma who were treated in this hospital from October 2019 to December 2021 were selected as the monitored group,and 101 healthy indi-viduals who underwent physical examinations a the same time were selected as the control group.Quantitative fluorescent PCR(qPCR)method was applied to detect the expression levels of miR-186-5p and miR-942-5p in serum,and multivariate COX regression was applied to analyze the prognostic factors of glioma patients.Re-ceiver operating characteristic(ROC)curve and area under curve(AUC)were used to analyze the diagnostic value of serum miR-186-5p and miR-942-5p in glioma.Kaplan-Meier survival curve was used to analyze the re-lationship between serum miR-186-5p and miR-942-5p expression and prognosis of patients.Results The ex-pression level of serum miR-186-5p in monitored group was lower than that in the control group(P＜0.05),and the expression level of miR-942-5p was higher than that in the control group(P＜0.05).The AUC of ser-um miR-186-5p and miR-942-5p in the diagnosis of glioma alone and in combination were 0.735,0.809 and 0.895,respectively.There were significant differences in the proportion of low miR-186-5p expression and high miR-942-5p expression in serum of patients with different preoperative Karnofsky performance status(KPS)scores,World Health Organization(WHO)grades and local infiltration(P＜0.05).The 2-year surviv-al rate of patients with high expression of miR-186-5p was higher than that of patients with low expression of miR-186-5p(x2=6.455,P=0.011).The 2-year survival rate of patients with high miR-942-5p expression was lower than that of patients with low miR-942-5p expression(x2=9.858,P=0.002).miR-186-5p was a protective factor for mortality in glioma patients(P＜0.05),while miR-942-5p was a risk factor(P＜0.05).Conclusion Serum miR-186-5p expression level decreases and miR-942-5p expression level increases in glioma patients,both of which have certain diagnostic value for the occurrence of glioma.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of children with refractory nephrotic syndrome （RNS） based on the real world by meta-analysis. METHODS A systematic search was conducted on CNKI， Wanfang， VIP， PubMed， Embase， Web of Science， the Cochrane Library， and CINAHL databases to strictly screen the literature and evaluate their quality. A meta-analysis was performed on the extracted literature data using R 4.2.2 and RStudio software. RESULTS A total of 26 real-world studies were included in this study， involving 996 children with steroid-dependent nephrotic syndrome/frequente-relapse nephrotic syndrome （SDNS/FRNS） and 205 children with steroid-resistant nephrotic syndrome （SRNS）. The results of the meta-analysis showed that the complete remission （CR） rate of RTX treatment for RNS was 46% （95%CI： 37%-56%）， the partial remission （PR） rate was 22% （95%CI： 14%-31%）， and the discontinuation rate was 35% （95%CI： 25%-44%）. The results of subgroup analysis showed that the CR rate of RTX treatment in SDNS/FRNS children was 49% （95%CI： 37%-62%）， PR rate was 25% （95%CI： 0-50%）， discontinuation rate was 41% （95%CI： 29%-52%）； the CR rate in SRNS children was 42% （95%CI： 27%-56%）， PR rate was 22%（95%CI： 12%-32%）， discontinuation rate was 21% （95%CI： 4%-38%）. The recurrence rate in children with SDNS/FRNS was 39% （95%CI： 21%-57%） within 1 year or less， 18% （95%CI： 18%-98%） in 2 years and more. As for safety， the majority of adverse reactions were mild infusion reactions， with an incidence of 13% （95%CI： 8%-22%）. Sensitivity analysis suggested that the results were robust. There was publication bias in mild infusion 20210908-BZ-CACM） reaction rate. CONCLUSIONS RTX is effective and safe in the treatment of RNS in children.

Objective To explore the value of systemic immune-inflammation index(SⅡ)in differentiating acute and chronic cholecystitis.Methods A total of 297 patients with cholecystitis who underwent cholecystectomy in Jinshan Hospital,Fudan University from August 2020 to November 2023 were selected,and were divided into acute cholecystitis group(n=192)and chronic cholecystitis group(n=105).The patients in acute cholecystitis group were further divided into severe subgroup(n=114)and mild subgroup(n=78).The differential diagnosis values of SⅡ and neutrophil-to-lymphocyte ratio(NLR)in acute and chronic cholecystitis were evaluated by ROC curve.Results Compared with chronic cholecystitis group,males were more,older,the incidence of hypertension was higher,drainage volume increased,drainage time,hospital time,and surgical duration were all longer,blood cells,neutrophil count,monocyte count increased,total bilirubin,direct bilirubin,and creatinine were higher,SⅡ and NLR increased in the acute cholecystitis group(P＜0.05).Compared with the severe subgroup,the drainage volume decreased,drainage time,hospital stay,and surgical duration were shorter,white blood cell count,neutrophil count,monocyte count,and total bilirubin decreased,while lymphocyte count increased,SⅡ and NLR decreased in the mild subgroup(P＜0.05).The optimal cutoff values of SⅡ and NLR for distinguishing acute cholecystitis from chronic cholecystitis were 797.96 and 3.65,and the AUC were 0.847 and 0.869,with 73.2％and 74.2％of sensitivity,and 86.7％and 89.5％of specificity.The optimal cutoff values of SⅡ and NLR for distinguishing acute severe cholecystitis from mild cholecystitis were 1 056.59 and 4.65,the AUC were 0.768 and 0.779,with 77.0％and 82.3％of sensitivity,and 67.5％and 62.3％of specificity.There was no statistically significant difference between the values of SⅡ and NLR for distinguishing acute severe and acute cholecystitis.Conclusion SⅡ is a good hematological indicator for distinguishing acute cholecystitis from chronic cholecystitis with similar value to NLR.

Objective:To assess the prevalence of dentinal hypersensitivity (DH) and related factors in urban adults in China.Methods:The study was designed as an observational, cross-sectional epidemiological study carried out in adults aged 18-69 years old in seven cities (Beijing, Shanghai, Wuhan, Chengdu, Xi′an, Guangzhou, and Harbin) of China. The study was conducted from March 2021 to May 2023. Patients were required to complete a questionnaire regarding the subjects′ socio-economic factors, dietary behavior, oral health behavior and personal antecedent factors. DH was clinically diagnosed by judging whether the tooth cold air stimulation provoked DH or not, and recorded by investigator pain rating Schiff score. Compare the findings of six cities (Harbin excluded) with a similar study conducted in 2008.Results:In total, 11 622 subjects from seven cities in China participated the study. Fifty two point two percent (6 072/11 622) of subjects reported DH in questionnaire, 36.7% (4 266/11 622) of subjects reported experiencing DH in response to cold air stimulation for at least one study tooth. Risk factors including age, sex, city, toothbrush method and acid reflux showed marked associations with DH ( P<0.05). The prevalence of DH of urban residents in six cities (Harbin excluded) was 33.7% (3 335/9 882), higher than that in 2008 [29.7%(2 354/7 939)]. Conclusions:Overall, DH was common among urban adults in China and the prevalence increased in recent years. Better understanding of DH and its associated factors should be considered in its prevention and management by dental professionals.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

Objective To investigate the vowel acoustic characteristics of patients with voice disorders and the reasonable way of administering vocal space area(VSA)and language in the Mandarin system.Methods A total of 40 subjects(20 males and 20 females)with voice disorder and normal healthy controls were recruited.The differ-ences in VSA between the disorder and healthy control groups were analyzed under different corpora and different vowel vertex numbers.Results The differences in VSA between the voice disorder and the control groups were highly significant in both the vowel and long sentence corpus.The differences in VSA between 4 vowels and 3 vow-els and 5 vowels were not significant,and 5 vowels were more suitable for VSA measurement in Mandarin.Conclu-sion The vowel articulation of patients with voice disorder is less clear than that of normal speakers.It is more ac-curate to use 5 vowels to measure VSA under the Mandarin system and it is better for measuring oral motility.Both single vowels and continuous speech are suitable for the measurement of VSA.