Objective:To explore the effects of anterior cruciate ligament (ACL) reconstruction combined with lateral extra-articular tenodesis (LET) on the postoperative knee stability in the patients with ACL injury combined with high grade pivot-shift phenomenon.Methods:A retrospective study was conducted to analyze the 62 patients with primary ACL injury and high-grade pivot-shift phenomena who had been treated and followed up for at least 1 year at Sports Medicine Center, The First Affiliated Hospital, Army Medical University between January 2021 and December 2022. There were 37 males and 25 females, with an age of (29.3±7.0) years. By the different treatment methods, the patients were divided into a trial group of 25 cases treated by ACL reconstruction plus LET and a control group of 37 cases treated by ACL reconstruction only. The International Knee Documentation Committee (IKDC) subjective score, knee Lysolm score, anterior-posterior stability of the knee (KT-1000 side-to-side disparity), rotational stability (axial shift test), and anterior subluxation of the lateral compartment (ASLC) were compared between preoperation and 1 year postoperation, as well as between the 2 groups.Results:There were no significant differences between the 2 groups in the preoperative general data, indicating comparability ( P>0.05). Surgical procedures went on uneventfully in all patients. At 1 year postoperatively in the trial group, the IKDC subjective score [(86.0±7.2) points] and Lysholm score [(87.1±6.0) points] were significantly higher than those in the control group [(81.8±6.8) points and (82.1±5.5) points], and the side-to-side disparity [0.7 (0.0, 2.0) mm] was significantly smaller than that in the control group [2.3 (0.0, 4.0) mm], the percentage of postoperative residual pivot-shift positivity [8.0% (2/25)] was significantly lower than that in the control group [32.4% (12/37)], and the ASLC [(4.5±2.6) mm] was significantly smaller than that in the control group [(6.2±2.6) mm] (all P<0.05). At 1 year postoperatively in both groups, the of IKDC subjective score,Lysolm score, side-to-side disparity, axial shift test, and ASLC were significantly better than the preoperative values ( P<0.05). Conclusion:In the treatment of the patients with ACL injury plus high grade pivot-shift phenomenon, compared with ACL reconstruction alone, ACL reconstruction plus LET enhances their postoperative knee stability and functional outcomes, reduces their residual rotational laxity, and improves their ASLC.

Objective To investigate the effect of miR-129-1-3p on the osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)and its potential mechanism.Methods Negative control group,the miR-129-1-3p mimic group,the miR-129-1-3p inhibitor group and the corresponding negative control were constructed and transfected into hBMSCs.The formation of calcium-mineralized nodules was observed by alkaline phosphatase staining and alizarin red S staining.The expression levels of miR-129-1-3p and osteogenic differentiation markers were detected by qRT-PCR.Western blot detected the protein expressions of bone mor-phogenetic protein 2(BMP2),SMAD1 and p-SMAD1.Results After transfection,the expression level of miR-129-1-3p in mimic group was significantly increased(P＜0.05),the number of mineralized nodules was significantly decreased,and the expression levels ofBMP2,Runt-related transcription factor 2(RUNX2),osteocalcin(OCN)mRNA were significantly down-regulated(P＜0.05).BMP2 and p-SMAD1 protein were also significantly down-regulated(P＜0.05)compared with Mimic-NC group.The expression levels of BMP2,RUNX2,OCN mRNA were significantly up-regulated in inhibitor group(P＜0.05)compared with Inhibitor-NC group.BMP2 and p-SMAD1 protein were significantly up-regulated in inhibitor group(P＜0.05).Conclusion miR-129-1-3p can inhibit the osteo-genic differentiation of human bone marrow mesenchymal stem cells by suppressing BMP2/SMAD1 signaling pathway.

Objective To investigate the association between single nucleotide polymorphisms(SNP)rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia(CIN).Methods A total of 96 patients diagnosed with CIN were randomly collected as the CIN group,and 225 healthy individuals examined during the same period were selected as the control group using SPSS software.Genotyping of the above SNP loci was performed using the TaqMan probe method,and their correlation with CIN was analyzed.Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group,with the frequency of the allele A in the CIN group significantly lower than that in the control group(P<0.001;OR=0.48,95%CI:0.32～0.70).In the dominant model,individuals carrying the G allele(A/G-G/G)had a significantly increased risk of CIN(P<0.001;OR=2.67,95%CI:1.64～4.37).In contrast,no correlation was found between the rs6864584 and the risk of CIN.Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

Objective: To create a prediction model for stroke risk among middle-aged and elderly populations, so as to provide a basis for early identification of high-risk population for stroke. Methods: From October to December 2023, residents aged ≥45 years in Chongchuan District, Nantong City, Jiangsu Province were selected using a multi-stage stratified random sampling method. The demographic information, life behavior, and chronic disease data were collected through a questionnaire survey. The standardized prevalence of stroke was calculated using data from the seventh National Population Census. The subjects were randomly divided into the training set and the internal validation set according to the ratio of 8∶2. The basic demographic information, life behavior, and chronic diseases of residents aged ≥45 years in Rugao City were collected from July to August 2023 as the external validation set. Predictive factors were selected using multivariable logistic regression model, and a nomogram for stroke among residents aged ≥45 years was established. The prediction effect was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and Hosmer-Lemeshow goodness of fit test. Results: A total of 6 290 residents aged ≥45 years were included, including 2 975 males (47.30%) and 3 315 females (52.70%). The average age was (61.90±10.20) years. The prevalence of stroke was 3.80%, and the standardized prevalence was 3.36%. The multivariable logistic regression showed that age, smoking, hypertension, and hyperlipidemia were predictors of stroke risk among residents aged ≥45 years, and the prediction model was ln[p/(1-p)]=-4.619+0.046×age+0.383×smoking+0.887×hypertension+0.678×hyperlipidemia. The AUC values of the training set, internal validation set, and external validation set were 0.748, 0.755, and 0.738, respectively. The consistency indexes were 0.748, 0.755, and 0.738, respectively. The Hosmer-Lemeshow goodness of fit test showed a good fitting effect (P>0.05). Conclusion The prediction model based on age, smoking, hypertension, and hyperlipidemia has good discrimination and calibration, and can be used to predict the risk of stroke among middle-aged and elderly populations aged ≥45 years.

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.