1.Role of ferroptosis in fibrosis: From mechanism to potential therapy
Xuemeng QIU ; Qing BI ; Jiyue WU ; Zejia SUN ; Wei WANG
Chinese Medical Journal 2024;137(7):806-817
Fibrosis, which is a manifestation of the physiological response to injury characterized by excessive accumulation of extracellular matrix components, is a ubiquitous outcome of the repair process. However, in cases of repetitive or severe injury, fibrosis may become dysregulated, leading to a pathological state and organ failure. In recent years, a novel form of regulated cell death, referred to as ferroptosis, has been identified as a possible contributor to fibrosis; it is characterized by iron-mediated lipid peroxidation. It has garnered attention due to the growing body of evidence linking ferroptosis and fibrogenesis, which is believed to be driven by underlying inflammation and immune responses. Despite the increasing interest in the relationship between ferroptosis and fibrosis, a comprehensive understanding of the precise role that ferroptosis plays in the formation of fibrotic tissue remains limited. This review seeks to synthesize previous research related to the topic. We categorized the different direct and indirect mechanisms by which ferroptosis may contribute to fibrosis into three categories: (1) iron overload toxicity; (2) ferroptosis-evoked necroinflammation, with a focus on ferroptosis and macrophage interplay; and (3) ferroptosis-associated pro-fibrotic factors and pathways. Furthermore, the review considers the potential implications of these findings and highlights the utilization of ferroptosis-targeted therapies as a promising strategy for mitigating the progression of fibrosis. In conclusion, novel anti-fibrotic treatments targeting ferroptosis could be an effective treatment for fibrosis.
2.Molecular epidemiological analysis of group A rotavirus in diarrhea cases in children under 5 years of age in Guangdong Province,2021-2022
Cai-Xia LI ; Chang ZHANG ; Wei ZHANG ; Han-Ri ZENG ; Huan-Ying ZHENG ; Bo-Sheng LI ; Bi-Xia KE
Chinese Journal of Zoonoses 2024;40(9):834-840
This study investigated the epidemiological and genotypic characteristics of group A rotavirus(RVA)in children under 5 years of age with diarrhea at a viral diarrhea surveillance sentinel hospital in Guangdong Province from 2021 to 2022,to provide a basis for RVA prevention and control.A total of 1 858 fecal samples from children under 5 years of age with diarrhea in 2021-2022 were collected.Rotavirus antigen was detected with ELISA,and positive samples were further sequenced and categorized.Among the 1 858 samples,156 were RVA positive.The positivity rates in boys and girls were 8.76%and 7.87%,respectively.Significant differences were observed in the detection rates of RVA infection among age groups.The rate of RVA infection increased gradually from December to April of the following year.In 2021,the main endemic strains of RVA in the Guangdong region were of the G9P[8]subtype,and the rare G8P[8]subtype increased in China.In 2022,the G8P[8]subtype surpassed the G9P[8]subtype for the first time.In cases of diarrhea in infants younger than 5 years in Guangdong Province from 2021 to 2022,the RVA genotypes were diverse,the G9P[8]genotype significantly decreased,and the G8P[8]subtype became a dominant genotype.Continuous RVA genotype monitoring remains necessary to assess the risk of RVA-related disea-ses.
3.Changes in Neutrophil Percentage-to-Albumin Ratio and Its Relationship with Short-Term Prognosis in Patients with Multiple Myeloma Treated with VRD
Xiao-Long LI ; Bi-Wei WANG ; Hui SUN ; Hong-Tao LIU ; Xi CHEN ; Huan WANG
Journal of Experimental Hematology 2024;32(6):1759-1763
Objective:To analyze the dynamic changes of neutrophil percentage-to-albumin ratio (NPAR) during treatment with bortezomib-lenalidomide-dexamethasone (VRD) in patients with multiple myeloma (MM),and explore the relationship between NPAR value and short-term prognosis of MM patients. Method:The data of 80 MM patients who underwent VRD chemotherapy at Tangshan Workers Hospital from January 2019 to April 2021 were retrospectively analyzed. NPAR levels were measured before VRD chemotherapy (T0),and on the first day of the third (T1),sixth (T2),and eighth (T3) chemotherapy cycles. All patients were followed up for 1 year,with the recurrence,progression,or death occurring within 1 year after the completion of VRD treatment as the endpoint event. The patients were divided into a good prognosis group and a poor prognosis group based on the follow-up results. The changes in NPAR at T0,T1,T2,and T3 in the two groups were statistically analyzed. The restricted cubic spline method was used to analyzed the relationship between NPAR and adverse short-term prognosis in MM patients undergoing VRD chemotherapy. Results:Among the 80 MM patients,25 cases (31.25%) had poor short-term prognosis,including 19 cases (23.75%) of progression or recurrence,and 6 cases (7.50%) of all-cause mortality. The levels of neutrophils and NPAR in the poor prognosis group at T0,T1,T2 and T3 were higher than those in the good prognosis group at the same period,while the albumin levels in the poor prognosis group at T0,T1,and T2 were lower than those in the good prognosis group at the same period (P<0.05);There was no significant difference in albumin levels between the poor prognosis group and the good prognosis group at T3 (P>0.05). Within the poor prognosis group and the good prognosis group,the levels of neutrophils and NPAR decreased sequentially at T0,T1,T2,and T3,while the levels of albumin increased sequentially,and the differences between each stage were statistically significant (P<0.05). The restricted cubic spline model showed an approximate J-shaped curve between the risk of poor short-term prognosis and the pre-treatment NPAR level in MM patients (P<0.05). If the pre-treatment NPAR>0.52,the risk of poor short-term prognosis in MM patients increased with the increase of NPAR value. Conclusion:After VRD treatment,the NPAR value of MM patients gradually decreases,and there is a correlation between the NPAR value before VRD treatment and the risk of poor prognosis after treatment. If NPAR>0.52 before treatment,the higher the NPAR value,the higher the risk of poor short-term prognosis in MM patients.
4.Effect of thoracic paravertebral nerve block on postoperative analgesia in patients undergoing CABG under general anesthesia: a meta-analysis
Ning XU ; Mingchao BI ; Wei RONG
Chinese Journal of Anesthesiology 2024;44(4):447-453
Objective:To systematically review the effect of bilateral thoracic paravertebral nerve block (TPVB) on postoperative analgesia in the patients undergoing coronary artery bypass grafting (CABG) under general anesthesia (GA) using a meta-analysis.Methods:A systematic search of PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, and VIP databases was performed, with a limited search period ending in December 2023. Randomized controlled trials regarding bilateral TPVB combined with GA versus GA alone for postoperative analgesia following CABG were included. The primary outcome was the rate of 24 h postoperative rescue analgesia. Secondary outcomes were intraoperative opioid consumption, incidence of intraoperative adverse reactions, indicators related to postoperative recovery, and incidence of postoperative adverse reactions. This meta-analysis was performed by using the " meta" package in R studio software.Results:A total of 9 papers ( n=788) were included. Compared to GA, bilateral TPVB combined with GA reduced intraoperative opioid consumption ( SMD=-1.88, 95% confidence interval [ CI] -2.80--0.96), decreased the rate of 24 h postoperative rescue analgesia ( RR=0.17, 95% CI 0.06-0.46) and the incidence of postoperative adverse reactions ( RR=0.39, 95% CI 0.25-0.60) and shortened postoperative extubation time ( MD=-1.52, 95% CI -2.01--1.03), postoperative intensive care unit stay ( MD=-4.40, 95% CI -5.29--3.51) and postoperative hospitalization time ( MD=-0.70, 95% CI -1.37--0.04). Conclusions:Bilateral TPVB can enhance the postoperative analgesic effect in the patients undergoing CABG under general anesthesia.
5.Chemical constituents from the leaves of Citrus reticulata and their anti-inflammatory activities
Fa-Ke YANG ; Xing YANG ; Zhi-Bi ZHANG ; Rui YIN ; Hong-Chuan ZHANG ; Xu-Li DENG ; Wei-Mao DONG ; Yi-Mou WANG ; Hong-Ping HE ; Fa-Wu DONG
Chinese Traditional Patent Medicine 2024;46(9):2972-2979
AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P<0.05,P<0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.
6.PI3K/Akt pathway-based investigation of total Astragalus saponins on sarcopenia in a rat model of type 2 diabetes mellitus
Lei-Lei MA ; Ji-An LI ; Wen-Xuan XU ; Jing-Ya WANG ; Zhao-Yang TIAN ; Jia-Yu LI ; Ru-Jie HAN ; Xiao-Jin LA ; Chun-Yu TIAN ; Hong CHANG ; Zi-Yang DAI ; Bi-Wei ZHANG
Chinese Traditional Patent Medicine 2024;46(11):3612-3619
AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P<0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P<0.05,P<0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P<0.05,P<0.01);decreased protein expressions of FoxO1 and Murf1(P<0.05,P<0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P<0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.
7.Constructing a diagnostic prediction model for antibody-mediated rejection after kidney transplantation based upon bioinformatics and machine learning algorithms
Jiyue WU ; Zejia SUN ; Qing BI ; Xuemeng QIU ; Wei WANG
Chinese Journal of Organ Transplantation 2024;45(10):718-727
Objective:To construct a diagnostic prediction nomogram for antibody-mediated rejection (AMR) after kidney transplantation (KT) based upon peripheral blood gene expression profiling and preliminarily screening potential drugs for AMR.Methods:Seven large kidney transplant cohort datasets related to AMR were retrieved from the database of GEO. Differential expression analysis was utilized for identifying differentially expressed genes between AMR and normal recipients. Multiple machine learning algorithms of random forest (RF), extreme gradient boosting (XGB), support vector machine (SVM) and generalized linear model (GLM) were employed for constructing diagnostic models for AMR after kidney transplantation. Receiver operating characteristic (ROC) curve was plotted for comparing the accuracy of each model. The key genes of optimal model were integrated for creating a diagnostic prediction nomogram for AMR. Calibration curve and decision curve analyses were employed for evaluating the accuracy of nomogram. The differentially expressed genes from biopsy tissues of AMR recipients were uploaded to the database of CMap for identifying potential therapeutic drugs through screening Top 5 compounds with opposite expression patterns to AMR.Results:Seven genes of CXCL10, FCGR1B, GBP5, CD69, LY96, BCL2A1 and EVI2A were over-expressed in both peripheral blood and biopsy tissues of AMR recipients. There were statistically significant differences with recipients without AMR (FDR<0.05). The AMR diagnostic model based upon RF algorithm demonstrated the highest AUC value (0.904) among various machine learning algorithms. Its AUC values were 0.876 and 0.824 in external datasets of GSE50084 and GSE175718. As for the diagnostic prediction nomogram constructed through integrating five key genes of BCL2A1, CXCL10, FCGR1BP, CD69 & EVI2A from RF model, calibration curve indicated that the predicted outcomes of nomogram approximated actual outcomes. Decision curve indicated that net benefit rate of nomogram was higher than that of extreme curves over a wide range of horizontal axis. The predicted results of CMap suggested that Top 5 compounds were raltegravir, rilmenidine, hydrastine, metyrapone and valproic acid.Conclusions:The nomogram constructed based upon peripheral blood gene expression profiling demonstrates high accuracy and generalizability in the diagnosis of AMR. As predicted by CMap, raltegravir, rilmenidine, hydrastine, metyrapone and valproic acid may be potential therapeutic drugs for AMR.
8.Progresses in electro-clinical aspects of restless sleep disorders
Chao WEI ; Xiaoli WANG ; Bi WANG ; Jiang ZHU ; Na YUAN ; Yonghong LIU
Chinese Journal of Neurology 2024;57(6):677-681
Restless sleep disorder was first reported in children, manifested with the large muscle groups movement during sleep named as large muscle movement. The movement of large muscle group refers to the non-periodic abnormal movement of large muscle group such as head, trunk and limbs during sleep period according to the criteria of American Sleep Association in 2022. The clinical and neuroelectrophysiological research progress of restless sleep disorder, interpretation and clinical significance of large muscles movement are summarized in this article.
9.Clinical efficacy of endovascular interventional therapy for spontaneous isolated superior mesen-teric artery dissection
Yu LI ; Rongjie ZHANG ; Wei SUN ; Yuxuan XIAO ; Xianru BI ; Yingxue HAO
Chinese Journal of Digestive Surgery 2024;23(6):845-852
Objective:To investigate the clinical efficacy of endovascular interventional therapy for spontaneous isolated superior mesenteric artery dissection(SISMAD).Methods:The retrospective cohort study was conducted. The clinical data of 87 patients with SISMAD who were admitted to The First Affiliated Hospital of Army Medical University from March 2012 to March 2023 were collected. There were 80 males and 7 femals, aged 54(49,61)years. Of 87 patients, 55 cases undergoing conservative therapy were allocated into conservative therapy group and 32 cases under-going endovascular interventional therapy were allocated into endovascular interventional therapy group. Observation indicators: (1) clinical characteristics; (2) treatment; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were represented as absolute numbers and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) clinical characteristics. There were significant differences in the cases with symptoms, percentage of neutrophils between the conservative therapy group and the endovascular interventional therapy group ( P<0.05). There was no significant difference in the proportion of Yun classification between the two groups ( P>0.05). (2)Treatment. There were significant differences in the complete vascular remodeling, duration of hospital stay, and total expenses between the conservative therapy group and the endovascular interventional therapy group ( χ2=23.752, t=-4.213, -16.421, P<0.05). There were 34 patients in the conservative therapy group and 24 patients in the endovascular interventional therapy group with relieved abdominal pain, respectively, showing no significant difference between the two groups ( P>0.05). For symptomatic patients in the conservative therapy group, symptoms including abdominal pain, nausea, vomiting, diarrhea, hematochezia were relieved or disappeared, and no intestinal ischemia or rupture occurred. For patients in the endovascular interventional therapy group, 30 cases were implanted stents, the operation time was 115(86,155)minutes, volume of intraoperative blood loss was 5(5,10)mL, dose of contrast media was (200±51)mL. There were 23, 8 and 1 cases with the contrast medium as Iodoxanol, Ioprosamide, Iodohexanol, respectively. About the surgical methods, 14 patients received single bare stent implantation, 3 cases received bare stent-assisted coil embolization, 10 cases received multiple bare stent implantation, 3 cases received covered stent implantation, 2 cases received angiography alone. A total of 39 self-expandable bare metal stents and 3 self-expandable covered stents were implanted. The diameter and length of the stents were (6.5±1.0)mm and (69±23)mm, respectively. Two asymptomatic patients had failure in endovascular interventional therapy and underwent superior mesenteric artery angiography. For the endovascular interventional therapy group, 92.3%(24/26) of patients were relieved abdominal pain and 2 patients with abdominal pain were improved after symptomatic treatment. (3) Follow-up. All the 87 patients were followed up for 12(4,24)months, without recurrent abdominal pain or secondary intervention. During the follow-up, 82 patients underwent computed tomography angiography or ultrasonography, and 5 patients had no available results. There was no SISMAD related death or superior mesenteric artery rupture. Eight patients in the conservative therapy group achieved complete vascular remodeling, versus 21 cases in the endovascular interventional therapy group, showing a significant difference between the two groups ( χ2=23.752, P<0.05). Conclusions:Compared with conservative therapy, patients undergoing endovascular interventional therapy for SISMAD has loner hospital stay, higher total costs, higher complete vascular remodeling rate. There is no recurrent abdominal pain in two methods.
10.A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection
Zhan ZENG ; Mingfang ZHOU ; Yanjie LIN ; Xiaoyue BI ; Liu YANG ; Wen DENG ; Tingting JIANG ; Leiping HU ; Mengjiao XU ; Lu ZHANG ; Wei YI ; Minghui LI
Chinese Journal of Hepatology 2024;32(2):113-118
Objective:To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection.Methods:A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data.Results:A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z ?=?-1.981, P ?=?0.048), aspartate aminotransferase (AST, z ?=?-3.956, P ?0.001), HBV load ( z ?=?-15.292, P ?0.001), and HBeAg ( z ?=?-4.77, P ?0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion:Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

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