1.Palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis: A new target for anti-myocardial fibrosis.
Xuewen YANG ; Yanwei ZHANG ; Xiaoping LENG ; Yanying WANG ; Manyu GONG ; Dongping LIU ; Haodong LI ; Zhiyuan DU ; Zhuo WANG ; Lina XUAN ; Ting ZHANG ; Han SUN ; Xiyang ZHANG ; Jie LIU ; Tong LIU ; Tiantian GONG ; Zhengyang LI ; Shengqi LIANG ; Lihua SUN ; Lei JIAO ; Baofeng YANG ; Ying ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4789-4806
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
2.Clinical efficacy of transcatheter tricuspid valve replacement in cardiac implantable electronic lead-related tricuspid regurgitation: A multi-center retrospective cohort study
Jingyi CAO ; Xiaoping NING ; Ning LI ; Fan QIAO ; Fan YANG ; Bailing LI ; Guangwei ZHOU ; Lin HAN ; Zhiyun XU ; Fanglin LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):818-825
Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.
3.Syndrome Differentiation and Treatment of Children Bronchiolitis Obliterans by Stages from the Perspective of Phlegm,Stasis,Block and Deficiency
Ya ZOU ; Tingjun LI ; Hongbing WANG ; Xiaoping JING
Journal of Traditional Chinese Medicine 2024;65(21):2264-2268
It is believed that children bronchiolitis obliterans (BO) is located at the lung and closely related to the spleen and kidney. Phlegm, stasis, block and deficiency are the main pathogenesis. This article promotes staged differentiation and treatment of BO considering the clinical manifestations and pathogenesis characteristics. The attack stage is dominated by phlegm and stasis blocking the lung, for which the method of dissolving phlegm and dispelling stasis, relieving cough and calming panting should be used; Xiaoqinglong Decoction(小青龙汤) and Sanzi Yangqin Decoction (三子养亲汤) with modifications and selfmade Modified Wuhu Decoction (五虎汤加味) are recommended for cold-phlegm blocking the lung syndrome and phlegm heat blocking the lung syndrome, respectively. In sustained stage, the upper excess and lower deficiency together with phlegm-stasis blocking the lung are the pathogenesis, for which the method of dissolving phlegm and dispelling stasis, reopening the block and supplementing deficiency is suggested, and Xiaoqinglong Decotion (小青龙汤) and Duqi pills (都气丸) with modifications can be used. In convalescent stage, the pathogenesis is lung-spleen-kidney depletion with residual pathogen. It suggested to supplement the deficiency and consolidate the root, as well as clear the residual pathogen, for which Baogen NO.1 Decoction (宝根1号方) with modifications can be used.
4. Construction and application of inflammatory bowel disease cohort database
Xiaoping WU ; Tao ZHENG ; Jingyuan FANG ; Jinlu TONG ; Zhijun CAO ; Yuqi QIAO
Chinese Journal of Gastroenterology 2023;28(4):237-242
Under the organization of Renji Hospital, Shanghai Jiao Tong University School of Medicine, a specialized disease database of inflammatory bowel disease (IBD) cohort was deployed, and a brief introduction of the database was made in this article. The IBD data set was established by referring to domestic and foreign standards. Through data extraction, cleaning, normalization and other information processing technologies, data from multi‑source heterogeneous platform were arranged to form a specialized major disease database of IBD cohort and the efficiency and quality of data collection in clinical practice, teaching and scientific research were guaranteed. The display and personalized export capacities of the database can promote the researches on IBD and assist the clinical decision‑making. It provides not only efficient, comprehensive and reliable research‑level data support for scientific research, but also a precise guidance for diagnosis and treatment of the disease. Furthermore, it can excavate the potential clinical principles based on medical big data.
5.Modified Wuhutang Alleviates Airway Inflammation and Down-regulates Expression of Muc5AC, STAT3, NF-κB, and NLRP3 in Lung Tissues of RSV-infected Asthmatic Mice
Linlin YU ; Jing WANG ; Ya ZOU ; Weiwei CHENG ; Xiaoping JING
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(19):108-115
ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin (Muc) 5AC, signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB), and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in respiratory syncytial virus (RSV)-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control (CON), asthma (ovalbumin, OVA), RSV infection-induced asthma (OVA+RSV), high-, medium-, and low-dose (4.08, 2.04, 1.02 g·kg-1·d-1, respectively) modified Wuhutang, and dexamethasone (Dxms, 0.1 g·kg-1d-1) groups (n=10). The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions (1.0 × 106 PFU·mL-1, 50 μL). Wuhutang was administrated by gavage, and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration, and then the lung tissue was stained by hematoxylin-eosin (HE) and Van Gieson (VG) for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated (p)-STAT3, STAT3, p-NF-κB, NF-κB, and NLRP3. ResultCompared with the CON group, the OVA group presented airway inflammatory cell infiltration, tissue hyperemia and edema, and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group, modified Wuhutang alleviated the airway inflammatory cell infiltration, tissue hyperemia and edema, and collagen fiber deposition, and the high-dose group had the best performance. Compared with the CON group, the OVA group and the OVA+RSV group showed increased expression level of Muc5AC (P<0.01). Compared with the OVA+RSV group, modified Wuhutang reduced the expression level of Muc5AC, and the reduction was significant in the high-dose group (P<0.05). Compared with the high-dose modified Wuhutang group, Dxms lowered the expression level of Muc5AC (P<0.05). Compared with the CON group, the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3, p-NF-κB, and NLRP3 (P<0.05, P<0.01). Compared with the OVA+RSV group, modified Wuhutang down-regulated the protein levels of p-STAT3, p-NF-κB, and NLRP3 (P<0.01). Compared with the high-dose modified Wuhutang group, the Dxms group showed up-regulated levels of p-STAT3, p-NF-κB proteins (P<0.01). ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC, p-STAT3, p-NF-κB, and NLRP3 in RSV-infected asthmatic mice, which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.
6.Expression levels of HBV pregenomic RNA and hepatitis B core-related antigen in circulating serum and their association with recurrence in chronic hepatitis B patients after withdrawal from nucleos(t)ide analogues
Shiwan ZHANG ; Xing CHEN ; Jiao LIU ; Min ZHAO ; Xiaoping MEI
Journal of Clinical Hepatology 2023;39(1):56-62
Objective To investigate the expression levels of HBV pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in circulating serum of chronic hepatitis B (CHB) patients after withdrawal from nucleos(t)ide analogues (NUC), as well as the correlation of HBV pgRNA and HBcrAg levels in circulating blood in different periods of time with recurrence in CHB patients after drug withdrawal. Methods Among the patients who attended the outpatient service of Affiliated Hospital of North Sichuan Medical College from December 2019 to July 2022, a total of 108 CHB patients who received anti-HBV therapy for at least 5 years and met the criteria for drug withdrawal in 2017 EASL Guidelines were enrolled. According to the time of drug withdrawal, the patients were divided into 4-, 12-, and 24-week groups after drug withdrawal, and according to the presence or absence of recurrence, they were divided into recurrence group and non-recurrence group. Quantitative real-time PCR was used to measure the level of HBV pgRNA in circulating serum of CHB patients; ELISA was used to measure the expression level of HBcrAg in peripheral venous blood; quantitative real-time PCR was used to measure HBV DNA load with high accuracy. The t -test was used for comparison of continuous data between two groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Pearson correlation test was used to investigate the correlation between the indices in circulating blood. Results For the CHB patients after drug withdrawal, the recurrence rate was 17.1% at 4-12 weeks, cumulative recurrence rate reached 29.3% after 24 weeks of follow-up, the patients with positive HBV DNA alone accounted for 64.3% and 60.0%, respectively, those with positive HBeAg alone accounted for 28.5% and 20.0%, respectively, and those with positive HBV DNA and HBeAg accounted for 7.1% and 20.0%, respectively. The expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum of CHB patients at 24 weeks after drug withdrawal were significantly higher than those at the time of drug withdrawal and at 4 weeks after drug withdrawal, and there was a significant difference between groups at different time points (all P < 0.05). Compared with the non-recurrence group, the recurrence group had significantly higher expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum ( t =2.549, 8.654, and 27.429, all P < 0.05), and further analysis of the recurrence group showed that the levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum at 12-24 weeks were significantly higher than those at 4-12 weeks (all P < 0.05). At the time of drug withdrawal, the recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg in circulating serum than the non-recurrence group ( t =18.561 and 6.152, both P < 0.001). The Pearson correlation analysis showed that in the recurrence group after drug withdrawal, HBV pgRNA and HBcrAg were positively correlated with HBV DNA in circulating serum ( r =0.82 and 0.66, both P < 0.001), while no such correlation was observed in the non-recurrence group ( r =0.14 and 0.04, both P > 0.05). Conclusion The recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg than the non-recurrence group at the time of drug withdrawal, suggesting that the levels of HBV pgRNA and HBcrAg in the CHB patients of the non-recurrence group at the time of drug withdrawal may be used as the reference thresholds for safe drug withdrawal in CHB patients, and measurement of HBV pgRNA and HBcrAg may be one of the potential reference indicators for the selection of anti-HBV treatment endpoints in the future.
7.Clinical Observation of Modified Yinqiaosan Combined with Antibiotics in Treatment of Acute Tonsillitis in Children with Wind-heat Invading Lung Syndrome
Jinghua QIAO ; Linlin YU ; Xiaoping JING ; Xiaoyan DONG ; Mingda GU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):121-125
ObjectiveTo observe the clinical effect of modified Yinqiaosan combined with antibiotics in the treatment of acute tonsillitis in children with wind-heat invading lung syndrome. MethodA total of 96 children with acute tonsillitis of wind-heat invading the lung syndrome were randomized into control group and observation group. The control group was treated with routine antibiotics, and the observation group was treated with modified Yinqiaosan and antibiotics for 7 days. The scores of major symptoms (sore throat, erythmatous throat, dysphagia, erythmatous tonsils and suppuration) and minor symptoms (fever, cough, stool, and tongue) and the levels of inflammation- and immune-related indexes [white blood cell (WBC), C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), and interferon-γ (IFN-γ)] were compared between two groups. ResultThe data of 92 children were statistically analyzed: 45 in the observation group and 47 cases in the control group. The total clinical effective rate of the observation group was 95.56%, as compared with the 93.62% of the control group. After treatment, the scores of major symptoms in the observation group were lower than those in the control group (P<0.05), and the scores of cough, defecation, and tongue in the observation group were lower than those in the control group (P<0.05). The levels of inflammation- and immune-related indexes after treatment in the observation group were lower than those before treatment (P<0.05). Except IFN-γ, the levels of the inflammation- and immune-related indexes in the control group were lower than those before treatment (P<0.05). After treatment, the levels of SAA and IL-6 in the observation group were lower than those in the control group (P<0.05). ConclusionModified Yinqiaosan combined with antibiotics can significantly reduce the expression of SAA and IL-6 in the treatment of children with acute tonsillitis, thereby alleviating inflammation and clinical symptoms and improving prognosis.
8.Expert statement on the construction criteria of critical care department in municipal and district designated hospitals under the pandemic prevention and control
Ruilan WANG ; Jiao LIU ; Ke MA ; Zhixiong WU ; Jian LU ; Lei LI ; Shaolin MA ; Jun GUAN ; Bin XU ; Yiqi YU ; Xiaoping SHAO ; Xiaoxiao MENG ; Yuan GAO ; Wenhong ZHANG ; Dechang CHEN
Chinese Critical Care Medicine 2022;34(6):561-570
The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.
9.Liver quality standards and donor scoring system for citizen organ donation after death
Rui HE ; Yingbin HUANG ; Ming HAN ; Xiaoping WANG ; Jian ZHOU ; Xiaopeng YUAN ; Yitao ZHENG ; Gang CHEN ; Yuan LIAO ; Jingdong LI ; Xiaofeng ZHU ; Qiang TAI ; Jiefu HUANG ; Xingyuan JIAO
Chinese Journal of General Surgery 2022;37(11):801-806
Objective:To establish donor liver quality related risk factors for the loss of function of transplanted liver.Methods:The data of donors and recipients of liver transplantation at the Organ Donation and Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University from Nov 2011 to Dec 2018 were analyzed retrospectively. Propensity score matching (PSM) was performed to evaluate and screen the data of donors and recipients, in order to balance the covariates.Results:Of the organ donation, there were 70 males and 20 females , aging (40.6±16.3) years. Of the liver transplantation recipients, there were 70 males and 20 females , aging (41.8±20.3) years. Liver dysfunction after transplantation was significantly correlated with the following variables: the donor's CPR time( t=0.429, P=0.000), 15-minute retention rate of indocyanine green ( χ2=67.151, P=0.000), liver function grading ( χ2=54.154, P=0.000), bullae fatty liver grading ( χ2=8.120, P=0.017), vesicular fatty liver grading ( χ2=16.000, P=0.001), ICU stay time ( χ2=14.900, P=0.001)and serum creatinine level ( χ2=44.685, P=0.000). The donor scoring system was established in our studying. For the 90 organ donation cases, the donated liver quality were classified into four levels,which were of good correspondence to the prognosis of the recipients. Conclusion:This donor scoring system and grading standards established by analyzing the high-risk factors of liver dysfunction after transplantation helps evaluate the quality of donor liver in China.
10.Analysis of the influencing factors of fatigue after stent implantation in patients with airway stenosis
Miao XU ; Xinwei HAN ; Xiaoping LOU ; Dechao JIAO ; Zhen YU ; Yahua LI ; Ziling JIA ; Zongming LI
Chinese Journal of Modern Nursing 2020;26(18):2508-2512
Objective:To explore the influencing factors of fatigue after stent implantation in patients with airway stenosis.Methods:Totally 104 patients with airway stenosis hospitalized in a hospital from July 2016 to June 2019 were selected, and all the patients were planned to received stent implantation. The patients were evaluated with Identity-Consequence Fatigue Scale (ICFS) postoperatively, and divided into the fatigue group and the non-fatigue group according to the evaluate results. The data of the two groups were consulted, and their gender, age, primary tumor, combined underlying disease, postoperative physical activity, pathological staging, history of radical surgery before stenting, preoperative radiotherapy and chemotherapy, degree of stenosis, type of stenosis, infiltration juga, stent placement site, and re-intervention after stenting were analyzed. Univariate and Logistic regression analysis were performed over the above influencing factors.Results:All the 104 patients with airway stenosis completed postoperative fatigue evaluation. The total score of ICFS was (82.16±8.07) . The scores of postoperative fatigue, attention, vitality, energy, daily activities and the total score were higher than those before operation, and the differences were statistically significant ( P<0.01) . Among the 104 patients with airway stenosis, 28 developed postoperative fatigue, with an incidence of 26.92%. Univariate and multivariate Logistic analysis revealed that postoperative physical activity, pathological staging, infiltrating and re-intervention after stenting were the main influencing factors to fatigue after stent implantation in patients with airway stenosis ( P<0.05) . Conclusions:Patients with airway stenosis have a high incidence of fatigue after stent implantation, which is affected by many factors. Effective intervention measures should be formulated according to the risk factors in order to reduce the incidence of postoperative fatigue.

Result Analysis
Print
Save
E-mail