This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

OBJECTIVE: To explore decompression strategies for lateral lumbar spinal stenosis under unilateral biportal endoscopy (UBE) assistance. METHODS: A clinical data of 86 patients with lateral lumbar stenosis treated with UBE-assisted intervertebral decompression between September 2022 and December 2023 was retrospectively analyzed. There were 42 males and 44 females with an average age of 63.6 years (range, 45-79 years). The disease duration ranged from 6 to 14 months (mean, 8.5 months). Surgical levels included L _{2, 3} in 3 cases, L _{3, 4} in 26 cases, L _{4, 5} in 42 cases, and L ₅, S ₁ in 15 cases. According to Lee's grading system, there were 21 cases of grade 1, 37 cases of grade 2, and 28 cases of grade 3 for lumbar spinal stenosis. Based on the location of stenosis and clinical symptoms, the 33 cases underwent interlaminar approach, 7 cases underwent interlaminar approach with auxiliary third incision, 26 cases underwent contralateral inclinatory approach, and 20 cases underwent paraspinal approach; then, the corresponding decompression procedures were performed. Visual analogue scale (VAS) score was used to evaluate lower back/leg pain before operation and at 1 and 3 months after operation, while Oswestry disability index (ODI) was used to evaluate spinal function. At 3 months after operation, the effectiveness was evaluated using the modified MacNab evaluation criteria. The spinal stenosis and decompression were evaluated based on Lee's grading system using lumbar MRI before operation and at 3 months after operation. RESULTS: All procedures were successfully completed with mean operation time of 95.1 minutes (range, 57-166 minutes). Dural tears occurred in 2 cases treated with interlaminar approach with auxiliary third incision. All incisions healed by first intention. All patients were followed up 3-10 months (mean, 5.9 months). The clinical symptoms of the patients relieved to varying degrees. The VAS scores and ODI of lower back and leg pain at 1 and 3 months after operation significantly improved compared to preoperative levels ( P<0.05), and the indicators at 3 months significantly improved than that at 1 month ( P<0.05). According to the modified MacNab evaluation criteria, the effectiveness at 3 months after operation was rated as excellent in 52 cases, good in 21 cases, and poor in 13 cases, with an excellent and good rate of 84.9%. No lumbar instability was detected on flexion-extension X-ray films during follow-up. The Lee's grading of lateral lumbar stenosis at 2 days after operation showed significant improvement compared to preoperative grading ( P<0.05). CONCLUSION For lateral lumbar spinal stenosis, UBE-assisted decompression of the spinal canal requires the selection of interlaminar approach, interlaminar approach with auxiliary third incision, contralateral inclinatory approach, and paraspinal approach based on preoperative imaging findings and clinical symptoms to achieve better effectiveness.
Humans ; Spinal Stenosis/diagnostic imaging* ; Female ; Male ; Middle Aged ; Decompression, Surgical/methods* ; Aged ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Objective To evaluate the effect of manual massage on complications after endoscopic foam sclerotherapy injection for the treatment of internal hemorrhoids.Methods Consecutive 113 patients with grade Ⅰinternal hemorrhoids were prospectively enrolled and completed endoscopic foam sclerotherapy.The patients were randomly divided into a massage group(n=65)and a control group(n=68).Massage group performed manual perianal massage,Visual analogue scale(VAS)was used to evaluate perianal pain.The postoperative bleeding,short-term and long-term efficacy were also compared.Results The median VAS of 24 h postoperation was 1.0(0.0,3.0)in massage group,which was significantly lower than 2.0(1.0,4.0)in control group,the difference was statistically significant(P=0.014).The no bleeding rate of one week postoperation was 84.6％in massage group,which was significantly higher than 64.7％in control group,the difference was statistically significant(P=0.009).After 12 weeks,6 months and 12 months of follow-up,there were no significant differences in cure rate and remission rate between the two groups(P＞0.05).Conclusion Manual massage after endoscopic sclerosing agent injection is beneficial to relieve postoperative pain of grade Ⅰ internal hemorrhoids and reduce bleeding.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.