1.Effect of sodium-glucose cotransporter 2 inhibitor empagliflozin in alleviating uremic cardiomyopathy and related mechanism
Shi CHENG ; Yeqing XIE ; Wei LU ; Jiarui XU ; Yong YU ; Ruizhen CHEN ; Bo SHEN ; Xiaoqiang DING
Chinese Journal of Clinical Medicine 2025;32(2):248-258
Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM+EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P<0.01); UCM+EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P<0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P<0.05); ventricular remodeling was alleviated (P<0.05), though there was no significant improvement in systolic function in UCM+EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P<0.01); the myocardial pathology improved with reduced collagen deposition in UCM+EMPA group (P<0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P<0.01), while myocardial hypertrophy was alleviated in UCM+EMPA group (P<0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P<0.05), but downregulated in UCM+EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM+EMPA group (P<0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.
2.Exploring effective components and therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treatment of chronic non-atrophic gastritis by UHPLC-Q-TOF/MS combined with network pharmacology
Tao WEN ; Guangyang JIAO ; Mengpei ZHAO ; Xiaoqiang YUE ; Feng ZHANG ; Wansheng CHEN
Journal of Pharmaceutical Practice and Service 2025;43(9):455-462
Objective To investigate the effective components and therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treating chronic non-atrophic gastritis. Methods The primary and secondary ion fragments of chemical components of Chaihu-Guizhi-Ganjiang decoction were obtained by UHPLC-Q-TOF/MS. Comparing with reference standards and literature information, a comprehensive characterization of the chemical constituents of Chaihu-Guizhi-Ganjiang decoction was conducted. Then, the network pharmacology approach was applied to explore the therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treatment of chronic non-atrophic gastritis based on the components in plasma and verified by immunohistochemical results. Results A total of 24 absorbed components of Chaihu-Guizhi-Ganjiang decoction were characterized, including 11 flavonoid glycosides, 3 fatty acids, 3organic acids, 2 gingerols, 2 flavonoids and, 1 each of fatty aldehydes, triterpenoids and amino acids, which mainly acted on TNF-α, IL-6, STAT3, and PTGS2. It exerted therapeutic effects by modulating signaling pathways, including the IL-17 signaling pathway and the AGE-RAGE signaling pathway, etc. Conclusion This study provided the first exploration of the effective components and therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treatment of chronic non-atrophic gastritis by UHPLC-Q-TOF/MS, which could offer scientific references for its further research.
3.Atractylodin induces programmed necrosis of non-small cell lung cancer A549 cells and inhibits xenograft growth in nude mice by activating the RIPK1/RIPK3/MLKL signaling pathway
WANG Yibo ; JIAO Bin ; WANG Xiaoqiang ; CHEN Chixing ; ZENG Cimei
Chinese Journal of Cancer Biotherapy 2024;32(2):146-153
目的:探讨苍术素(ATR)通过调节受体相互作用蛋白激酶(RIPK)1/RIPK3/混合谱系激酶结构域样(MLKL)信号通路对非小细胞肺癌(NSCLC)A549细胞程序性死亡及裸鼠移植瘤生长的影响。方法:使用0~160 μmol/L的ATR处理A549细胞,MTT法检测细胞存活率以确定后续实验给药浓度。使用ATR和/或RIPK1抑制剂Nec-1(necrostatin-1)、caspase抑制剂Z-VAD-FMK处理A549细胞,验证ATR是否诱导A549细胞发生程序性坏死。将A549细胞分为对照组、ATR-L组、ATR-M组、ATR-H组(分别用0、10、20、40 μmol/L ATR处理)、ATR+Nec-1组(40 μmol/L ATR+50 μmol/L Nec-1处理),处理24 h后,采用PI单染及Hoechst33342/PI双染法检测细胞死亡情况、透射电镜观察细胞死亡形态、DCFH-DA荧光探针法检测细胞内ROS水平、JC-1染色法检测线粒体膜电位、WB法检测细胞中RIPK1/RIPK3/MLKL信号通路相关蛋白质的表达水平。构建A549细胞裸鼠移植瘤模型,用10 mg/kg ATR(溶于玉米油中)对裸鼠灌胃给药5周,观察ATR对移植瘤生长的影响,WB法检测移植瘤组织中RIPK1/RIPK3/MLKL信号通路相关蛋白质的表达水平。结果:10~160 μmol/L的ATR可显著抑制A549细胞增殖,选择10、20、40 μmol/L的ATR进行后续实验。ATR组A549细胞存活率显著低于对照组(P<0.01)和ATR+Nec-1组(P<0.01),而ATR+z-VAD组细胞存活率显著低于z-VAD组(P<0.01),说明ATR可诱导A549细胞发生程序性坏死而非凋亡。与对照组比较,ATR处理组A549细胞发生肿胀,线粒体内脊消失呈空泡化,细胞内容物向外泄漏,细胞核聚集,表现为坏死特征,ATR-L组、ATR-M组、ATR-H组A549细胞死亡率、ROS水平及p-RIPK1、p-RIPK3、p-MLKL表达水平均显著升高,线粒体膜电位显著降低(均P<0.01),且呈药物浓度依赖性;与ATR-H组比较,ATR+Nec-1组细胞死亡率、ROS及p-RIPK1、p-RIPK3、p-MLKL表达水平降低,线粒体膜电位显著升高(均P<0.01)。裸鼠移植瘤实验结果显示,与对照组比较,ATR组裸鼠移植瘤体积、移植瘤质量均降低(P<0.05,或P<0.01),而与瘤组织中p-RIPK1、p-RIPK3、p-MLKL蛋白表达水平均显著升高(均P<0.01)。结论:ATR可能通过激活RIPK1/RIPK3/MLKL信号通路诱导A549细胞发生程序性坏死,抑制A549细胞及其裸鼠移植瘤的生长。
4.Clinical progress of internal fixation in the treatment of femoral neck fracture in middle-aged and elderly patients
Tianjiao YAN ; Yujie JIN ; Chao SUN ; Xiaoqiang ZHOU ; Zhenquan XU ; Guangxiang CHEN ; Xiangxin ZHANG
International Journal of Surgery 2024;51(3):196-202
Middle-aged and elderly patients with femoral neck fracture often suffer from basic diseases. Conservative treatment will significantly increase the incidence of complications. At present, surgical treatment is mostly advocated. Internal fixation is one of the effective treatment methods for middle-aged and elderly patients with femoral neck fracture. It has the advantages of improving hip joint function, accelerating patient recovery, and improving patient quality of life. At present, there are many choices of internal fixation in the world, each has its own advantages and disadvantages, and there is no unified standard. Different surgical methods can be selected according to various factors such as fracture type, patient′s physical condition and surgical auxiliary technology. This article reviews the clinical progress of internal fixation for femoral neck fractures in middle-aged and elderly patients from four aspects: the characteristics of femoral neck fractures in middle-aged and elderly patients, common internal fixation methods, 3D printing guide plate auxiliary technology and artificial intelligence auxiliary technology.
5.Value of preoperative quantitative ultrasound analysis of quadriceps femoris in predicting chronic post-surgical pain after total knee arthroplasty
Xiaoqiang LI ; Wei CHEN ; Mingyue LI ; Tianchi SHAN ; Wen SHEN
Chinese Journal of Tissue Engineering Research 2024;28(9):1388-1393
BACKGROUND:Total knee arthroplasty is one of the effective methods to treat end-stage knee osteoarthritis.However,some patients still experience chronic post-surgical pain.It is significant to find out the influencing factors of chronic post-surgical pain.Demographic factors,social psychological factors and perioperative pain were the focus of previous studies,but muscle factors closely related to the occurrence and development of knee osteoarthritis were rarely reported. OBJECTIVE:To evaluate the value of preoperative quantitative ultrasound analysis of quadriceps femoris in predicting chronic post-surgical pain after total knee arthroplasty. METHODS:A total of 250 patients with knee osteoarthritis who underwent the first unilateral total knee arthroplasty under elective general anesthesia from January to August 2022 in the Affiliated Hospital of Xuzhou Medical University were selected.All patients were treated with the same anesthesia and operative methods.Before the surgery,clinical data were recorded,and the thickness and echo intensity of quadriceps femoris on the operated side were measured by ultrasound imaging,which could quantify the degree of quadriceps femoris atrophy.Multivariate logistic regression was used to analyze the independent factors affecting the occurrence of chronic post-surgical pain,and receiver operating characteristic curves were used to evaluate its predictive value. RESULTS AND CONCLUSION:(1)250 subjects were involved in the result analysis,and 91 of them had chronic post-surgical pain,with an incidence of 36.4%.(2)There were significant differences between the chronic pain and non-chronic pain groups in preoperative pain score during movement,preoperative Western Ontario and McMaster University Osteoarthritis Index,preoperative anxiety and depression scale score,preoperative muscle thickness and echo intensity of quadriceps femoris,and postoperative acute pain score(P<0.05).(3)Multivariate logistic regression analysis showed that preoperative thickness of quadriceps femoris was an independent protective factor for chronic post-surgical pain and preoperative pain score during movement was an independent risk factor for chronic post-surgical pain.(4)Receiver operating characteristic curves showed that the area under the curve of the preoperative thickness of quadriceps femoris was 0.625(95%CI:0.555-0.695),and the critical value was 2.78 cm,sensitivity was 0.802,specificity was 0.415.(5)It is concluded that the preoperative thickness of quadriceps femoris is an independent protective factor for chronic post-surgical pain,but its predictive efficacy is low,and its clinical application needs to be further verified or modified.
6.Screening and analysis of ferroptosis related genes in peripheral blood mononuclear cells of patients with systemic lupus erythematosus
Kang TAO ; Yuan TIAN ; Shifei LI ; Bing NI ; Xiaoqiang CHEN ; Zhifang ZHAI
Chinese Journal of Rheumatology 2024;28(2):93-98
Objective:To analyze the differentially expressed genes in PBMCs of patients with systemic lupus erythematosus (SLE) by bioinformatics methods screening and analyzing the key genes related to ferroptosis, and explore the possible mechanism of ferroptosis involved in the pathogenesis of SLE at the transcription level.Methods:The data sets and samples of healthy people (HC) and SLE patients who met the screening criteria were retrieved from the Gene Expression Omnibus (GEO), a sub-database of the National Center for Biotechnology Information (NCBI). The differentially expressed genes, GO enrichment analysis and KEGG pathway enrichment analysis were analyzed by GEO2R, R language and related software packages. The protein interaction network (PPI) of differential genes was analyzed by STRING, Cytoscape and other tools to explore the key genes and pathways. In addition, real-time quantitative reverse transcription PCR (RT-qPCR) was used to verify the expression of key genes. Mann-Whitney U test was used to compare the expression of key genes in PBMCs between the two groups. Spearman rank correlation analysis was used to explore the relationship between SLE disease activity and the level of key genes. Results:Six data sets were included in this study. A total of 166 genes related to ferroptosis were differentially expressed between SLE and HC groups. The differential genes were specifically expressed in alveolar macrophages, neutrophils, CD49 + cells and CD31 + cells. GO enrichment analysis and KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly involved in multiple signaling pathways closely related to SLE, such as oxidative stress response, infection and TNF signaling pathway. Hub genes screened by different algorithms all suggested RELA as a key gene, and RT-qPCR confirmed that compared with the RELA gene expression level in the HC group [0.75(0.37,1.13)], the expression level in SLE group [2.02 (1.19,4.06)] was increased, the difference was statistically significant ( Z=-3.08, P=0.002), and was positively correlated with the corresponding SLEDAI score of SLE samples ( r=0.52, P=0.019). Conclusion:The ferroptosis of many immune cells, including alveolar macrophages and CD49 + NK cells, is involved in the pathogenesis of SLE. RELA may be involved in the ferroptosis of PBMCs in SLE through the NF-κB pathway.
7.Arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint athrosis
Zhe ZHAO ; Hongli GENG ; Jianquan LIU ; Yongsheng LI ; Jianwen YIN ; Xiaoqiang CHEN ; Guanghui WANG ; Xiangyu CHENG ; Jiabei LI ; Zhiqin DENG ; Aozhengzheng DONG ; Manyi WANG ; Xiaofei ZHENG ; Wencui LI
Chinese Journal of Orthopaedics 2024;44(1):25-32
Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.
8.Expert consensus on the rational application of the biological clock in stomatology research
Kai YANG ; Moyi SUN ; Longjiang LI ; Zhangui TANG ; Guoxin REN ; Wei GUO ; Songsong ZHU ; Jia-Wei ZHENG ; Jie ZHANG ; Zhijun SUN ; Jie REN ; Jiawen ZHENG ; Xiaoqiang LV ; Hong TANG ; Dan CHEN ; Qing XI ; Xin HUANG ; Heming WU ; Hong MA ; Wei SHANG ; Jian MENG ; Jichen LI ; Chunjie LI ; Yi LI ; Ningbo ZHAO ; Xuemei TAN ; Yixin YANG ; Yadong WU ; Shilin YIN ; Zhiwei ZHANG
Journal of Practical Stomatology 2024;40(4):455-460
The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.
9.Predictive model of postoperative hypotension in patients undergoing hepatocellular carcinoma resec-tion with controlled low central venous pressure
Junxiong WU ; Xiaoqiang DU ; Kun CHEN ; Ji-Andong LIU
The Journal of Clinical Anesthesiology 2024;40(8):809-813
Objective To investigate the prediction model of hypotension in patients with hepato-cellular carcinoma resection using controlled low central venous pressure technique(CLCVP).Methods A total of 144 patients with liver cancer admitted from January 2020 to June 2023 were retrospectively ana-lyzed,including 81 males and 63 females,aged 45-64 years,BMI 22-26 kg/m2,ASA physical status Ⅰ or Ⅱ.144 patients were randomly divided into trial set(n=96)and verification set(n=48)according to 2:1.The trial set and verification set were divided into hypotensive group and non-hypotensive group ac-cording to whether hypotension occurred after operation.Preoperative albumin,preoperative hemoglobin,op-eration method,operation time,tumor site,tumor size,hilar block time,number of hilar block times,hilar block interval time,blood loss,mean intraoperative CVP,intraoperative fluid volume,and intraoperative u-rine volume were collected.Univariate and multivariate Logistic analysis were used to analyze the risk factors of hypotension in the experimental group,and a risk prediction model was established.The risk prediction model was verified in the validation group.Results There were 29 patients(30.2%)of postoperative hy-potension in the test group and 15 patients(31.3%)of postoperative hypotension in the validation group.Compared with the non-hypotensive group,the preoperative albumin in the hypotensive group was signifi-cantly decreased(P<0.05),the operation time was significantly prolonged,the ratio of tumor diameter≥5 cm,and the amount of blood loss were significantly increased(P<0.05).Multivariate analysis showed that preoperative albumin elevation(OR=0.216,95%CI 0.164-0.665,P<0.05)was an independent protective factor for postoperative hypotension.Prolonged operative time(OR=2.649,95%CI 1.802-7.553,P<0.05),tumor diameter≥5 cm(OR=3.789,95%CI 2.011-12.458,P<0.05),in-creased blood loss(OR=8.873,95%CI 2.750-17.553,P<0.05)was an independent risk factor for postoperative hypotension.According to the results of multi-factor analysis,the risk factors of postoperative hypotension in patients with controlled low central venous pressure hepatocellular carcinoma resection were established:F=-408.64-(1.534×preoperative albumin)+(0.974×operation time)+(1.332×tumor diameter≥5 cm)+(2.183×blood loss).The risk model was validated in the validation set,and the area under the ROC curve(AUC)was0.821(0.695-0.943),the sensitivity was71.7%,and the speci-ficity was 86.5%.The Hosmer-Lemeshow goodness of fit test showed that χ2=10.654,P=0.222.Conclusion Prolonged operative time,tumor diameter≥5 cm and increased blood loss are risk factors for hypotension after hepatocellular carcinoma resection using CLCVP technique,and higher preoperative albumin is protective factor.The establishment of risk prediction model through multi-factor analysis has good forecasting value.
10.Application of excel sheets combined with QR codes in precision navigation and location management of sterile instrument rooms in the operating room
Zhuang LIN ; Weishan HUANG ; Yan ZHANG ; Xiongqin CHEN ; Lianhua CHEN ; Xiaoqiang LIN ; Shihuan JIANG
Modern Hospital 2024;24(10):1531-1534
Objective To explore the effectiveness of using Excel sheets combined with QR codes for precision naviga-tion and location management of sterile instrument rooms in the operating room.Methods The study focused on the location management of nearly 1,000 sterile instruments in three sterile instrument rooms of our hospital.Instruments from July to Septem-ber 2023 were used as the control group,employing traditional location management methods.Instruments from October to De-cember 2023 were used as the observation group,applying Excel sheets and QR codes for precise navigation and location manage-ment.Results The time taken by new nurses and interns to find and retrieve sterile instruments decreased from(4.61±0.32 min)to(1.41±0.15 min).The accuracy of retrieving sterile instruments increased from 83.33%to 98.33%.The compliance rate for location management of sterile instruments improved from 75%to 100%.Nurse satisfaction increased from 81.67%to 96.67%,with significant differences observed(P<0.05).Conclusion The application of Excel sheets combined with QR codes for precision navigation and location management of sterile instrument rooms in the operating room effectively reduces re-trieval time for sterile instruments,decreases error rates,optimizes management processes,enhances work efficiency,avoids sur-gical delays,ensures patient safety,minimizes conflicts between medical staff and patients,and increases nurse satisfaction.This approach is worthy of clinical promotion and application.

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