ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

Objective : To investigate the effects of branched-chain amino acid(BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism. Methods : 3T3-L1 preadipocytes were divided into the Control, differentiation medium(DM), low-concentration BCAA, and high-concentration BCAA groups. A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations. Oil-red O staining was used to observe the formation of lipid droplets in adipocytes. Intracellular triglyceride(TG) and total cholesterol(TC) were detected by enzymatic method. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Stat3 and adipocyte differentiation-related genes. Results : CCK-8 results showed that the viability of 3T3-L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group, the low-concentration BCAA groups(0.5 and 1.0 mmol/L) had significantly larger intracellular lipid droplets, increased number of lipid droplets, and elevated levels of the intracellular TC(0.88vs0.68 mmol/g; 0.83vs0.68 mmol/g,P<0.01) and TG(0.77vs0.40 mmol/g; 0.62vs0.40 mmol/g,P<0.01). Nevertheless, the cell differentiation in the high-concentration group(5.0 and 10.0 mmol/L) significantly decreased compared with that in the DM group. Further, levels of PPARγ, C/EBPα, Adiponectin, and FABP4 mRNA and protein expression significantly increased in the low-concentration group, but significantly decreased in the high-concentration group than that in the DM group(P<0.01). In addition, low concentrations of BCAA promoted stat3 phosphorylation, while high concentrations inhibited its phosphorylation(P<0.01). Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3, i.e. low concentrations of BCAA induce cell differentiation by promoting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differentiation.

Objective:To analyze the molecular characteristics of antibiotic resistance in Helicobacter pylori(HP)and provide a molecular bio-logical basis for clinical eradication of HP by means of rational antibiotic use.Methods:From February 2019 to November 2023,1,144 pa-tients at the Gansu Wuwei Cancer Hospital who tested positive for HP using the 14C-urea breath test were enrolled in the study.Antibiotic resistance and related molecular characteristics of HP,and CYP2C19 polymorphisms in the patients were detected by diffusion drug suscept-ibility testing,drug resistance gene testing,and next-generation sequencing,respectively.Results:Among the six antibiotics assessed,the resistance rate and the prevalence of resistance genes(rdxA)were highest for metronidazole(92.00%and 86.12%,respectively),and lowest for amoxicillin(Pbp1)(11.78%and 37.11%,respectively).The prevalence of CYP2C19 alleles showed that 46.77%,44.58%,and 8.65%of par-ticipants were fast,medium,and slow metabolizers,respectively.Of the participants,148(18.55%)had immunohistochemical sphericity.The eradication rate of HP lower using conventional treatment regimens than that using personalized treatment regimens(χ2=8.627,P=0.003).The HP eradication rate was higher among patients with a first diagnosis of drug resistancebased on molecular testing,than that in patients undergoing retreatment(χ2=6.242,P=0.012).Conclusions:The prevalence of amoxicillin-resistant HP is low in Wuwei City,which has a high incidence of gastric cancer.Molecular diagnosis of antimicrobial resistance could improve the HP eradication rate and provide a refer-ence for rational use of antibiotics in clinical practice.

Objective To investigate the correlation of serum irisin level with insulin resistance and left ventricular remodeling after PCI in patients with ST-segment elevation myocardial infarction(STEMI)without diabetes.Methods A total of 485 STEMI patients without diabetes who received emergency PCI in our hospital from January 2017 to August 2020 were recruited in this study.According to the quartile values of baseline serum irisin levels,they were divided into low(＜0.31 mg/L,n=161),medium(0.31-0.97 mg/L,n=150),and high irisin groups(＞0.97 mg/L,n=174).Serum irisin level was measured with ELISA and insulin resistance was assessed by homeostasis model.During a follow-up of 12 months,the relationship between serum irisin level and echocardiographic parameters was evaluated.Results Compared with the baseline irisin level,the level reached a peak of at 8 h after PCI,and decreased a minimum at 3 d after surgery,with statistical differences(P＜0.01).The low irisin group had significantly higher BMI,diastolic blood pressure,fasting blood glucose,fasting insulin,TG,cTnI peak and NT-proBNP levels,but youn-ger age when compared with the medium irisin group and the high irisin group(P＜0.05).Obvi-ously higher diastolic blood pressure,fasting insulin,TG,cTnI peak and NT-proBNP levels were observed in the medium irisin group than the high irisin group(P＜0.05).Pearson correlation analysis showed that baseline serum irisin level was negatively correlated with HOMR-IR,ΔLVEDD,ΔLVESD,ΔLVEDVi and ΔLVESVi(r=-0.338,r=-0.172,r=-0.164,r=-0.154,r=-0.167,P＜0.01).Multiple linear regression analysis indicated that after further ad-justment for impaired glucose tolerance and BMI,low irisin level was still independently associat-ed with ΔLVEDD(P＜0.01).Conclusion Baseline irisin level in STEMI patients without diabetes is correlated with insulin resistance and subsequent poor left ventricular remodeling,and is expec-ted to be a predictor of left ventricular remodeling after PCI.

OBJECTIVE To investigate the effects of astilbin （AST） on myocardial ischemia-reperfusion injury （MIRI） in rats and its potential mechanism. METHODS SD male rats were randomly divided into sham operation group， model group， positive control group （Compound Salvia miltiorrhiza tablets， 240 mg/kg）， AST low-dose and high-dose groups （30， 90 mg/kg）， and high- dose of AST+hypoxia-inducible factor-1α（HIF-1α） inhibitor group （AST 90 mg/kg+2ME2 15 mg/kg）， with 25 rats in each group. Except for sham operation group， MIRI model was induced in other groups， and then given relevant drug or normal saline intragastrically or intraperitoneally， for consecutive 28 d. Serum contents of cardiac troponin I （cTnI） and creatine kinase isoenzyme （CK-MB） were detected； volume ratio of myocardial infarction was measured； the pathological changes of myocardium， the apoptotic rate of myocardial cells and ultrastructure of mitochondria in myocardial tissue were all observed. The contents of tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6） and malondialdehyde （MDA）， the activity of superoxide dismutase （SOD）， the expressions of HIF-1α， adenovirus E1B interacting protein 3 （BNIP3） and myosin-like Bcl-2 interacting protein （Beclin1） were determined in myocardium. The ratio of microtubule-associated protein light chain 3 （LC3） Ⅱ to Ⅰ （LC3 Ⅱ/Ⅰ） in rat myocardium was calculated. RESULTS Compared with model group， no obvious swelling was found in the myocardial tissue of rats in positive control group， AST low-dose and high-dose groups， and the myocardial fibers were arranged regularly； the volume ratio of myocardial infarction， the contents of cTnI， CK-MB， TNF-α， IL-6 and MDA， the apoptotic rate were decreased significantly （P＜0.05）， while SOD activity， protein expressions of HIF-1α， BNIP3 and Beclin1， LC3Ⅱ/Ⅰ were increased significantly （P＜0.05）. HIF-1α inhibitor could significantly weaken the improvement effect of AST on the above indicators in MIRI model rats （P＜0.05）. CONCLUSIONS AST enhances mitochondrial autophagy by activating HIF-1α/BNIP3 signaling pathway， thereby reducing MIRI in rats.

OBJECTIVE: To compare the effectiveness between the posterolateral approach and the posterolateral combined posteromedial approaches in the treatment of Mason type 2B posterior malleolar fracture. METHODS: A retrospective analysis was performed on the clinical data of 79 patients with posterior ankle fracture who met the selection criteria between January 2015 and January 2022. There were 62 cases of Mason 2B Pilon subtype and 17 cases of avulsion subtype. Among Mason 2B Pilon subtype patients, 35 were treated with posterolateral approach (group A), 27 patients were treated with combined approach (group B). There was no significant difference in gender, age, injured side, cause of injury, time from injury to operation, preoperative hospital stay, preoperative visualanalogue scale (VAS) score, and intraoperative internal fixation between the two groups ( P>0.05). All patients with Mason 2B avulsion subtype were treated by posterolateral approach, including 7 males and 10 females, aged from 25 to 68 years, with an average of 46.1 years. The operation time, intraoperative blood loss, postoperative hospital stay, and complications were recorded. The reduction quality was evaluated by Ovadia deals radiographic score, and the ankle function and pain were evaluated by VAS score, American Orthopaedic Foot and Ankle Society (AOFAS) score, and ankle range of motion. RESULTS: Mason 2B Pilon subtype: There was no significant difference in operation time, intraoperative blood loss, postoperative hospital stay, and follow-up time between the two groups ( P>0.05). The radiological evaluation of Ovadia deals in group A was significantly worse than that in group B ( P<0.05). The VAS score in the two groups significantly improved at each time point after operation, and the VAS score and AOFAS score further improved with the extension of time after operation, and the differences were significant ( P<0.05). Except that the AOFAS score of group A was significantly lower than that of group B at last follow-up ( P<0.05), there was no significant difference in VAS score and AOFAS score between the two groups at other time points ( P>0.05). At last follow-up, the ankle range of motion in group A was significantly less than that in group B ( P<0.05). There was no significant difference in the incidence of sural nerve injury, deep tissue infection, limitation of toe movement, and traumatic ankle arthritis between the two groups ( P>0.05). Mason 2B avulsion subtype: The operation time was (119.47±20.61) minutes and the intraoperative blood loss was 50 (35, 55) mL. Seventeen patients were followed up 13-25 months, with an average of 18 months. The Ovadia deals score was excellent in 10 cases, good in 6 cases, and poor in 1 case at 1 week after operation, and the excellent and good rate was 94.1%. All fractures healed in 8-18 weeks with an average of 12.35 weeks. There were 1 case of sural nerve injury and 3 cases of traumatic ankle arthritis after operation. No deep tissue infection or limitation of toe movement occurred. The VAS score decreased significantly and AOFAS score increased significantly with time, and the differences were significant between different time points before and after operation ( P<0.05). The ankle range of motion at last follow-up was (56.71±2.47)°. CONCLUSION Compared with the posterolateral approach, the combined approach is a better choice for the treatment of Mason 2B Pilon subtype. If the posteromedial bone block does not affect the reduction of the medial malleolus, the posterolateral approach can achieve good effectiveness for Mason 2B avulsion subtype.
Female ; Humans ; Male ; Ankle Fractures/surgery* ; Arthritis/etiology* ; Fracture Fixation, Internal/adverse effects* ; Postoperative Hemorrhage ; Retrospective Studies ; Tibial Fractures/surgery* ; Treatment Outcome ; Adult ; Middle Aged ; Aged

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

Objective:To determine the expression of transmembrane protein 45A (TMEM45A) in keloid tissues and fibroblasts, and to evaluate its effect on extracellular matrix (ECM) synthesis by keloid-derived fibroblasts (KFs) .Methods:Samples of surgically excised keloid and normal foreskin tissues were collected from the Department of Dermatology and Department of Urology of Yanbian University Hospital from January 2019 to December 2020, and TMEM45A protein expression was determined in keloid tissues and KFs by Western blot analysis. KFs were divided into TMEM45A-specific small interfering RNA (siRNA) group and control siRNA group to be transfected with the TMEM45A-specific siRNA and control siRNA respectively. Then, Western blot analysis was performed to evaluate the effects of down-regulation of the TMEM45A gene on the expression of myofibroblast marker protein (α-smooth muscle actin) and ECM-related proteins.Results:Compared with normal skin tissues (1.00 ± 0.11) and fibroblasts (1.00 ± 0.20), TMEM45A expression levels significantly decreased in keloid tissues (0.26 ± 0.05) and KFs (0.41 ± 0.09), respectively ( t = 10.76, 4.75, P < 0.001, = 0.009, respectively). The expression levels of α-smooth muscle actin, ECM-related type Ⅰ collagen, type Ⅲ collagen, and fibronectin were significantly higher in the TMEM45A-specific siRNA group than in the control siRNA group ( t = -5.98, -4.57, -4.90, -7.19, P = 0.004, 0.010, 0.008, 0.002, respectively) . Conclusion:Lowly expressed TMEM45A in keloids may play an important role in the pathogenesis of keloids by promoting ECM synthesis.

OBJECTIVE To investigate the effects of a spirin （Asp） on myocardia l ischemia/reperfusion （I/R） injury by regulating microRNA -340-5p （miR-340-5p）/high mobility group box 1 （HMGB1）/Toll-like receptor 4 （TLR4） pathway. METHODS Male SD rats were divided into sham operation （Sham）group（thoracotomy without ligation ），I/R group （I/R injury model was constructed ），and Asp pretreatment （I/R+Asp）group（7 d of Asp pretreatment+modeling ），I/R+Asp+in-miR-340-5p group [Asp pretreatment 7 d+transfection with miR -340-5p inhibitor 48 h before modeling+modeling ] and I/R+Asp+HMGB 1 group （7 d of Asp pretreatment+transfection with overexpression of HMGB 1 48 h before modeling+modeling ），with 20 rats in each group. The levels of myocardial injury indexes [lactate dehydrogenase ，creatine kinase isoenzyme -MB，cardiac troponin Ⅰ]， inflammation and oxidative stress indexes [myeloperoxidase，superoxide dismutase ，glutathione peroxidase ，malondialdehyde] were detected in each group ，and the pathological changes of myocardial tissue were observed . The myocardial infarction area ，cell apoptosis and the expression of miR -540-5p，HMGB1 and TLR 4 in myocardial tissue were detected . Cardiomyocyte H 9C2 of rats was used as the object to investigate the targeting relationship between miR -340-5p and HMGB 1. RESULTS Asp pretreatment could significantly inhibit the increase of serum myocardial injury indexes in I/R model rats ，reduce inflammation and inhibit oxidative stress ，reduce myocardial infarct size and apoptosis ，and significantly up -regulated the expression of miR -340-5p and down-regulated the expression of HMGB 1 and TLR 4 proteins（P＜0.05）；inhibition of miR -340-5p or overexpression of HMGB 1 could reverse the above protective effects of Asp （P＜0.05）. miR-340-5p could target and negatively regulate HMGB 1 expression （P＜0.05）. CONCLUSIONS Asp can reduce inflammation and oxidative stress by regulating the miR -340-5p/HMGB1/TLR4 pathway，reduce apoptosis i n myocardial tissue ，and play a protective role against myocard ial I/R injury .

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3