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.Prognostic Value of Radiation-Induced Lymphopenia in Patients with Unresectable Primary Hepatocellular Carcinoma Receiving Radiotherapy
Jinlong TONG ; Haiyu WANG ; Xiaoqiang TIAN ; Ying LI ; Shihui LU ; Wei YE
Cancer Research on Prevention and Treatment 2024;51(12):1007-1014
Objective To evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. Methods The clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. Results The baseline and min ALC of 98 patients during radiotherapy were 1.52×109/L and 0.45×109/L, respectively(P<0.001). The optimal cut-off value of min ALC for the prediction of the one-year survival rate was 0.38×109/L. GTV, the mean dose of the liver and spleen, the V5 and V10 of the liver and spleen, and the V15 of the spleen were correlated with min ALC, and the V5 of the liver was an independent predictor of min ALC. The overall survival of patients with high min ALC was higher than that of patients with low min ALC. Independent prognostic factors were min ALC≤0.38×109/L (HR=0.515, P=0.024), min ALC≥grade 3 (HR=0.576, P=0.032), tumor thrombus in the portal/vena cava, Child-Pugh grade A, increase of ≥2 points in the Child-Pugh score after radiotherapy, and received more than two other therapies. Conclusion Min ALC≤0.38×109/L and min ALC≥grade 3 have independent prognostic value in patients with unresectable hepatocellular carcinoma receiving radiotherapy.
3.Impact of optimizing stroke green channel on treatment efficiency of acute ischemic stroke treatment efficiency in a county hospital
Yao WANG ; Lei SHI ; Guangbu LI ; Qiyun ZHU ; Xiaoqiang WU ; Maolin LU ; Haiyang LIN ; Wei QI ; Wei GAO ; Ruiyin ZHOU ; Qifeng LU ; Baodong WU
Chinese Journal of Clinical Medicine 2024;31(6):971-976
Objective To evaluate the impact of optimizing the stroke green channel on the efficiency of acute ischemic stroke management in a county hospital. Methods A retrospective analysis of the emergency stroke green channel treatment data from Sixian People’s Hospital from May 2020 to April 2021 (before optimization of the green channel) and from May 2021 to April 2022 (after optimization of the green channel) was conducted. The rates of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) patients, as well as door-to-needle time (DNT), door-to-puncture time (DPT), and the modified Rankin scale (mRS) scores of patients three months post-treatment before and after the optimization of the stroke green channel were compared. Results Within one year before and after optimization of the green channel, the number of acute visits for ischemic stroke was 3 143 and 2 623, respectively. Before optimization, 84 and 51 underwent IVT and MT, respectively. After optimization of the green channel, the ratios of patients underwent IVT (n=215) and MT (n=103) significantly increased, and both DNT and DPT were significantly shortened (P<0.000 1); the proportion of MT patients with an mRS score of 0-2 at 3 months post-discharge significantly increased (46/99 vs 13/46, P=0.038). Conclusion After optimizing the green channel at Sixian People’s Hospital, the efficiency of stroke treatment has significantly improved, and the patients’ prognosis improved.
4.Analysis of the Current Status and Prospects of Multi-Omics Technologies in the Field of Traditional Chinese Medicine
Hongye PENG ; Chunli LU ; Xiaoqiang HUANG ; Shuxia HUANG ; Mo ZHAO ; Jing LIU ; Wenliang LV
Journal of Traditional Chinese Medicine 2024;65(8):775-781
Due to the complexity of traditional Chinese medicine (TCM) interventions and the diversity of herbal components, single-omics technologies such as genomics, transcriptomics, proteomics, and metabolomics often cannot comprehensively elucidate the scientific connotations of TCM. Multi-omics technologies driven by system biology can analyze the theoretical connotations and application mechanisms of TCM from different levels such as genes, gene expression, proteins, and metabolites, in line with the holistic view of TCM, which helps to promote the modernization of TCM. By reviewing the literature on the application of omics technologies in the field of TCM, it is found that multi-omics technologies have been widely used in TCM for syndrome differentiation, evaluation of herbal quality, elucidation of pharmacological mechanisms, and drug toxicity assessment, providing comprehensive explanations of the mechanisms of action of TCM and overcoming the limitations of single-omics technologies, and having obtained significant achievements. However, multi-omics technologies also face challenges such as high cost, difficulties in data analysis due to large data volumes, and insufficient translation of research results. In the future, it is expected that through strengthening interdisciplinary cooperation, conducting long-term and dynamic clinical research, standardizing and normalizing data analysis processes, adopting appropriate and reasonable multi-omics integration patterns, establishing multi-omics databases for TCM, revealing the individualized characteristics, therapeutic mechanisms, and disease regulatory networks of TCM, the modernization of TCM will be promoted.
5.Preliminary evaluation of surgical treatment for postpartum diastasis recti
Lu LIU ; Xiaoqiang ZHU ; Nan LIU ; Jiajie LIU ; Rui TANG
Journal of Surgery Concepts & Practice 2024;29(4):329-335
Objective To evaluate the clinical efficacy,safety and the postoperative functional improvement of the surgical treatment for postpartum diastasis recti(PDR).Methods A retrospective study was conducted on the patients with PDR who underwent surgical treatment in Department of Hernia and Abdominal Wall Surgery,Shanghai East Hospital,Tongji University from November 2018 to October 2023.The patients'demography,operation data,postoperative complications,recurrence and functional evaluation before and after surgery were analyzed.Results A total of 39 cases were included.Open surgery was performed in 21 cases,laparoscopic surgery in 17 cases,and hybrid surgery in 1 case.On the basis of linear alba reconstruction(LAR),26 cases were additionally repaired with Sublay mesh,9 with Onlay,and 1 with intraperitoneal onlay mesh(IPOM);the other 3 cases were only performed with LAR.The follow-up ranged 6-45 months,and the completion rate was 92.3%.During the follow-up,no recurrence was observed,and the overall complication rate was 20.5%,including 1 case with delayed wound healing,2 cases with seroma,and 5 cases with skin disorders in paraumbilical and subumbilical area.There were significant changes of European Registry for abdominal wall hernias quality of life(EuraHS QoL)score and Oswestry disability index(ODI)after operation,indicating significant improvement in QoL and lower back pain.The inter-recti distance(IRD)of the patients undergoing laparoscopic surgery was less than that of the patients undergoing open surgery(median 4.0 cm vs.4.5 cm),and the duration of hospital stay of the patients undergoing laparoscopic surgery was shorter than that of open surgery(median 7 days vs.9 days).Conclusions In general,the surgical treatment of PDR is safe and effective,and it can not only correct the separation,but also improve QoL and lower back pain of the patients.Tailored surgical procedures should be selected for patients with different conditions.
6.Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy
Pengjie JI ; Qiongjiao LU ; Xiaoqiang CHEN ; Yuebing CHEN ; Xiane PENG ; Zhiwei CHEN ; Cheng LIN ; Shaojun LIN ; Jingfeng ZONG
Cancer Research and Treatment 2023;55(4):1113-1122
Purpose:
This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT).
Materials and Methods:
A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test.
Results:
There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT.
Conclusion
Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.
7.Theraputic Effect and Quality of Life Assessment in Patients with Neuropathic Pain Due to Bone Metastasis from Hepatocellular Carcinoma Treated with Radiotherapy and Pregabalin
Jinlong TONG ; Xiaoqiang TIAN ; Ying LI ; Shihui LU ; Lixue WANG ; Haiyu WANG
Cancer Research on Prevention and Treatment 2023;50(12):1214-1220
Objective To evaluate the short-term efficacy and quality of life of primary hepatocellular carcinoma patients after radiotherapy and pregabalin treatment for neuropathic pain with bone metastasis. Methods 32 patients with primary hepatocellular carcinoma bone metastases were treated with radiotherapy combined with pregabalin treatment.Then, we prospectively studied the analgesic efficacy for neuropathic pain and quality of life, used the brief pain inventory and douleur neuropathique 4 questionnaire (DN4) to evaluate pain at baseline, one and two months after radiotherapy, assessed pain response using the international consensus endpoint definition of bone metastasis, and used European Organization for Research and Treatment of Cancer Research and Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and bone metastasis module (QLQ-BM22) for quality of life assessment. Results One and two months after radiotherapy, the average DN4 score of neuropathic pain decreased, and the objective pain relief rates were 62.8% and 68.6%, respectively.The physical, emotional, social, and role functional scores of EORTC QLQ-C30 functional scale significantly increased in the first month after radiotherapy.Symptom scale of pain (
8. Application of population modeling analysis to evaluate the impact of gene polymorphism on drug PK/PD
Lu LIU ; Yufei SHI ; Qingfeng HE ; Weimin CAI ; Xiaoqiang XIANG ; Fengyan XU ; Kun WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1275-1282
Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD.
9.Association between mitochondrial dysfunction and hepatocellular carcinoma
Xiaoqiang GAO ; Shi ZUO ; Xiaodong JIA ; Yinying LU
Journal of Clinical Hepatology 2022;38(6):1436-1439
Hepatocellular carcinoma (HCC) is a type of tumor with a high incidence rate, a low rate of early diagnosis, and poor prognosis, and its development and progression involve many factors. As an important organelle in cells, mitochondria is the "energy factory" of cells and is one of the main sites for the production of reactive oxygen species in vivo, and it also participates in the regulation of cell apoptosis. There are varying degrees of changes in mitochondrial membrane, oxidation respiratory chain, mitochondrial dynamics, mitochondrial DNA, and mitochondrial calcium homeostasis during the development and progression of HCC, and such changes may affect the progression of HCC. This article systematically elaborates on the association between mitochondria and HCC, so as to provide a new direction for the diagnosis and treatment of HCC.
10.Research advances in sodium taurocholate cotransporting polypeptide in hepatobiliary diseases
Xiaoqiang GAO ; Shi ZUO ; Xiaodong JIA ; Yinying LU
Journal of Clinical Hepatology 2022;38(5):1179-1182
Sodium taurocholate cotransporting polypeptide (NTCP) is not only an important transporter for bile acid absorption into the liver, but also a functional receptor for HBV and HDV, and extensive studies have been performed for its structure, function, gene characteristics, and expression and regulation mechanisms. NTCP is also associated with chronic viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, primary biliary cholangitis, and hepatocellular carcinoma. This article elaborates on the role of NTCP in various hepatobiliary diseases, so as to provide new direction for the diagnosis and treatment of related diseases.

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