1.Inhibitory Effects of the Slit Guidance Ligand 1-3’ Untranslated Region on the Fibrotic Phenotype of Cardiac Fibroblasts
Ya WANG ; Huayan WU ; Yuan GAO ; Rushi WU ; Peiying GUAN ; Hui LI ; Juntao FANG ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):466-474
ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region (3’UTR) of slit guidance ligand 1 (Slit1) (Slit1-3’UTR) on the fibrotic phenotypes of cardiac fibroblasts (CFs) and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs (mCFs). The expression of fibrosis-related genes in mCFs, such as collagen type 1 alpha1(COL1A1), collagen type 3 alpha3 (COL3A1) and alpha smooth muscle actin (α-SMA) were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ (Ang Ⅱ) was used to treat mCFs, and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt, miR-34a-5p mimic was transfected into mCFs, followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt, and the levels of miR-34a-5p and its target gene SIRT1(si-SIRT1) in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes, proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs, while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes, and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.
2.Discussion on right lung volume reduction techniques in lung transplantation surgery
Hongyi WANG ; Yixing LI ; Jinteng FENG ; Heng ZHAO ; Yanpeng ZHANG ; Shan GAO ; Jizhao WANG ; Shuo LI ; Guangjian ZHANG
Organ Transplantation 2025;16(6):907-913
Objective To investigate the clinical effects of different right lung volume reduction techniques when the donor lung is oversized and mismatched with the recipient. Methods Clinical data of 10 recipients who underwent right lung volume reduction lung transplantation at the First Affiliated Hospital of Xi'an Jiaotong University from October 2022 to June 2024 were collected, including gender, age, primary disease type, and type of transplantation. A retrospective analysis was performed on postoperative complications within 90 days, duration of mechanical ventilation, hospital stay, and survival status to explore the impact of different volume reduction techniques on the survival rate of lung transplant recipients. Results A total of 10 right lung volume reduction recipients were included in this study, with 2 cases of upper lobe reduction, 7 cases of middle lobe reduction, and 1 case of lower lobe reduction. Three recipients developed airway complications (one each with upper, middle, and lower lobe reduction). The 30-day survival rate was 90% and the 1-year survival rate was 70%. One recipient with upper lobe reduction died of septic shock during the perioperative period, one with lower lobe reduction died of airway anastomotic fistula 2 months after surgery, and one with middle lobe reduction died of renal insufficiency 1 year after surgery. All 7 recipients with middle lobe reduction successfully passed the perioperative period, with one case of airway anastomotic stenosis (1/7). The average duration of mechanical ventilation was 71 hours, and the average hospital stay was 26 days. The 30-day survival rate was 7/7, and the 1-year survival rate was 6/7. Conclusions Middle lobe reduction in right lung transplantation surgery has the advantages of low incidence of airway complications, good safety, and minimal loss of lung function, and may be a better right lung volume reduction option with potential for application.
3.Advances in metabolic reprogramming in heart failure
Lei HUANG ; Wen-Wen LI ; Pei-Wen WENG ; Shan GAO
Chinese Pharmacological Bulletin 2024;40(8):1418-1423
Adenosine triphosphate(ATP)production in cardio-myocytes in healthy heart depends primarily on the oxidative phosphorylation of fatty acids and,to a lesser extent,on the oxi-dation or glycolysis of glucose.Patients with heart failure devel-op severe disturbances in energy metabolism,including disturb-ances in substrate uptake and utilization,oxidative phosphoryla-tion,and ATP shuttling,resulting in inadequate cardiac energy supply.By intervening in energy metabolism pathways,cardiac efficiency can be increased,energy production deficits can be reduced,and cardiac function can be improved in patients with heart failure.We hence have reviewed and outlined the mecha-nisms and therapeutic implications of metabolic changes during heart failure.
4.Application and research progress of interferon-α in antiviral therapy
Yan-Dong YAO ; Gao-Fu LI ; Li-Shan TIAN ; Yue GAO ; Wei ZHOU
Chinese Pharmacological Bulletin 2024;40(11):2010-2014
This review discusses the application,mechanism,challenges,and future research directions of interferon-α(IFN-α)in antiviral research and treatment.It provides an overview of the basic biological characteristics of IFN-α,including its mechanism of action in the antiviral immune response.The arti-cle explores the use of IFN-α in treating various viral diseases,such as COVID-19,chronic hepatitis C,and hepatitis B,high-lighting the challenges faced in clinical treatment.To address these challenges,it discusses the focus of future research.This review offers a comprehensive understanding of the application ofα-interferon in modern medicine,demonstrating its importance in the field of antiviral treatment,while also pointing out the limitations of current treatment practices and potential directions for future research.
5.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
6.Construction of discharge readiness assessment index for elderly patients after hip fracture surgery
Shan LI ; Jie SONG ; Mi SONG ; Chen QIU ; Yuan GAO
Chinese Journal of Modern Nursing 2024;30(6):707-712
Objective:To construct an evaluation index of discharge readiness suitable for elderly patients after hip fracture surgery in China, so as to provide a basis for the implementation of discharge readiness services for elderly patients after hip fracture surgery.Methods:From January 2018 to March 2023, a preliminary version of the discharge readiness evaluation indicators for elderly patients with hip fracture was constructed through literature search and semi-structured interviews. From April to May 2023, the Delphi method was used to select 19 experts from the medical and nursing fields to conduct two rounds of expert inquiries on various indicators. The final version of the discharge preparation evaluation indicators for elderly hip fracture patients was constructed through indicator screening and modification.Results:Through literature search and reading, 13 literatures were obtained. A total of 101 expert opinions were collected in two rounds of expert consultation, and the participation rate and questionnaire recovery rate of the two rounds of expert consultation were 100.00% (19/19). The judgment coefficient and familiarity coefficient of the two rounds of expert consultation were 0.979 and 0.832, respectively, and the expert authority coefficient were both 0.905.The Kendall's harmony coefficients of the two rounds of expert correspondence were 0.154 and 0.157, respectively ( P<0.01). The final evaluation index of discharge readiness of elderly patients with hip fracture included three primary indexes and 12 secondary indexes. Conclusions:The evaluation index of discharge readiness of elderly patients after hip fracture surgery established in this study is scientific and reliable, providing a basis for accurately assessing discharge readiness of elderly patients after hip fracture surgery.
7.Analysis of Clinical Characteristics and Prognosis of AML Patients with Co-Mutation of CEBPA Gene and GATA2 Gene
Xue-Wei YANG ; Shan-Shan LI ; Yan-Hua SU ; Jia-Yue SUN ; Yu-Juan GAO
Journal of Experimental Hematology 2024;32(5):1313-1316
Objective:To analyze the clinical characteristics and prognosis of patients with co-mutation of CEBPA gene and GATA2 gene,so as to facilitate clinicians to formulate more accurate individualized treatment plans for patients.Methods:A total of 43 acute myeloid leukemia(AML)patients with CEBPA double mutations and CEBPA-bZIP domain mutation admitted to the First Affiliated Hospital of Harbin Medical University from January 2017 to April 2022 were included,and the clinical characteristics and prognosis of patients with GA TA2 gene mutation among them were compared and analyzed.Results:The median age of patients with GA TA2 gene mutation was 48.0 years,which was significantly lower than 57.0 years of patients without GATA2 gene mutation(P<0.05).However,there were no significant differences in sex,white blood cell count,hemoglobin concentration,platelet count,immunophenotype,bone marrow and peripheral blood blast cell ratio and complete remission rate between the two groups(P>0.05).The median overall survival and event-free survival time of patients with GATA2 gene mutation were not reached,while those of patients without GATA2 gene mutation were 14.8 and 8.1 months,respectively(both P<0.05).Conclusion:The median age of patients with GATA2 gene mutation is lower than that of patients without GATA2 gene mutation.GATA2 gene mutation further prolongs the survival time of AML patients with CEBPA double mutations and CEBPA-bZIP domain mutation.
8.Chemical constituents from the large polar fraction of the roots of Lindera reflexa and their antitumor activities
Zhi-Hao TIAN ; Xiao-Ya SUN ; Shan-Shan ZHANG ; Zhi-Ning GAO ; Yan LI ; Ruo-Xi CHEN ; Sui-Qing CHEN
Chinese Traditional Patent Medicine 2024;46(8):2617-2623
AIM To study the chemical constituents from the large polar fraction of the roots of Lindera reflexa Hemsl.and their antitumor activities.METHODS The large polar fraction from the roots of L.reflexa was isolated and purified by silica gel column,Sephadex LH-20 gel column,semi-preparative HPLC and ODS medium pressure column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Thirteen compounds were isolated and identified as 2,6-dimethoxy-4-hydroxyphenyl-1-O-β-D-glucopyranoside(1),3-hydroxy-4,5-dimethoxyphenol-β-D-glucopyranoside(2),syringin(3),1-O-3,4-dimethoxy-5-hydroxyphenyl-(6-O-3,5-dimethoxygalloyl)-β-D-glucopyranoside(4),p-cymen-7-yl β-D-glucopyranoside(5),pisumionoside(6),staphylionoside D(7),dendranthemoside B(8),lynoiside(9),nudiposide(10),icariside B1(11),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(12),(+)-N-(methoxycarbonyl)-N-norboldine(13).Compounds 3 and 13 showed obvious cytotoxicity against human lung cancer cells(A549)and human gastric cancer cells(MGC80-3).CONCLUSION Compounds 1-13 are isolated from the roots of L.reflexa for the first time.Compounds 3 and 13 have good anti-tumor activities.
9.The expression of CD24 antigen in multiple myeloma patients and its predictive value after induction therapy
Mengru LIU ; Bin CHU ; Yuan CHEN ; Mengzhen WANG ; Minqiu LU ; Shan GAO ; Lei SHI ; Qiuqing XIANG ; Lijuan FANG ; Qi YAN ; Na JI ; Kai SUN ; Li BAO
Chinese Journal of Laboratory Medicine 2024;47(10):1178-1185
Objective:This study analyzed the expression of CD24 antigen on bone marrow plasma cells (BMPC) of patients with multiple myeloma (MM) and the predictive value of induction therapy.Methods:This clinical observational study utilized 258 MM patients samples treated at the Hematology Department of Beijing Jishuitan Hospital who met the inclusion criteria in the Department of Hematology, Capital Medical University, from August 12th, 2022 to February 1st, 2024. According to the different stages of the disease, patients were divided into three groups: 78 cases of Newly Diagnosed Multiple Myeloma(NDMM) (42 males and 36 females, aged 62±11), 56 cases of the relapse refractory group (34 males and 22 females, aged 64±9), and 124 cases of the disease remission group (68 males and 56 females, aged 62±10). Multiparameter flow cytometry (MFC) was used to detect the expression level of CD24 antigen on BMPC and the relationship between CD24 and MM disease status. The clinical data and test results of 78 NDMM patients at initial diagnosis were retrospectively analyzed, including gender, age, MFC detection of the positive expression rate of antigens (CD19, CD20, CD24, CD27, CD56), the results of efficacy evaluation after induction therapy, ISS staging, R-ISS staging, blood hemoglobin, β2-microglobulin, human serum albumin, serum creatinine, lactate dehydrogenas, correction of calcium, BMPC ratio, and the results of FISH. The patients were divided into a deep remission group [including complete remission (CR) and very good partial remission (VGPR)] with 43 cases and a non-deep remission group (non CR and VGPR) with 17 cases according to the difference of antigen positive expression rate after induction therapy. The differences of antigen expression on BMPC between the two groups were compared. Binary logistic regression was used to analyze the relationship between the expression of each antigen and the efficacy after induction therapy in patients, and the results showed that CD24 was more correlated with the achievement of deep remission after induction therapy than other antigens. Therefore, taking the positive expression rate of CD24 in NDMM patients at the initial diagnosis and deep remission after induction therapy as the research objects, the predictive value of CD24 for NDMM patients reaching deep remission after induction therapy was analyzed by using receiver operating characteristic curve (ROC), and the optimal cutoff value was obtained. NDMM was divided into two groups according to the cut-off value, and the differences between the two groups in clinical baseline data and prognostic indicators were compared.Results:The positive rates of plasma cell CD24 expression in the NDMM group, the relapse refractory group and the disease remission group were 2.18 (95% CI 0.08-81.85)%, 3.81 (95% CI 0.10-64.56)%, 8.74 (95% CI 0.79-95.55)% respectively. Compared with the disease remission group, the NDMM and relapse refractory group was lower ( Z=-7.889, -5.282, respectively, P<0.001). Univariate analysis showed that there was a significant difference in the positive expression rate of CD24 at initial diagnosis between the deep remission group and the non-deep remission group ( Z=-3.265, P<0.001), while there was no significant difference in CD19 ( Z=-0.271, P=0.787), CD20 ( Z=-0.205, P=0.837), CD27 ( Z=-0.582, P=0.560), and CD56 ( Z=-0.328, P=0.743) between the two groups. Binary logistic regression analysis showed that compared with other antigens [CD19 ( OR=1.045, 95% CI 0.975-1.120, P=0.217), CD20 ( OR=1.000, 95% CI 0.971-1.030, P=0.976), CD27 ( OR=0.997, 95% CI 0.977-1.016, P=0.734), CD56 ( OR=1.006, 95% CI 0.990-1.006, P=0.449)], the expression of CD24 ( OR=0.423, 95% CI 0.990-1.006, P=0.449) on BMPC in NDMM patients was most closely related to the achievement of deep remission was achieved after induction therapy. The lower the proportion of CD24 at the initial diagnosis was, the lower the probability of achieving deep remission after induction therapy was. The area under the curve (AUC) of CD24 in predicting deep remission after induction therapy was 0.772 (95% CI 0.655-0.889, P=0.001), with a sensitivity of 60.50%, a specificity of 85.00%, and the optimal critical value was 2.21%. Compared with the group with plasma CD24 positive rate>2.21%, the group with plasma CD24 positive rate<2.21% had a higher proportion of male (39.47%vs 65.00%, χ2=5.092, P=0.024), ISS stagingⅢ (41.67% vs 58.33%, χ2=6.175, P=0.046), β2 microglobulin (3.19 mg/L vs 4.14 mg/L, Z=-2.257, P=0.024), and BMPC [(8.672±1.827)% vs (19.530±3.188)%, t=-2.963, P=0.004] detected by MFC, and the differences were statistically significant. Conclusions:The low positive rate of plasma cell CD24 is closely related to the higher tumor burden and the worse disease status of MM patients. In addition, the positive expression rate of CD24 is at initial diagnosis can predict the efficacy achieved after induction therapy, and the lower positive rate of CD24 is, the worse the efficacy achieved after induction therapy. At the same time, MFC detection of CD24 is convenient and efficient in the evaluation and prediction of MM.
10.Clinical characteristics and treatment outcomes of chronic dacryocystitis-related corneal ulcers
Qing HUANG ; Fengmei SHAN ; Jie LI ; Xiaoyu ZHANG ; Xiuhai LU ; Fuhua WANG ; Hua GAO ; Xiaolin QI
Chinese Journal of Experimental Ophthalmology 2024;42(5):442-447
Objective:To analyze the clinical characteristics and treatment outcomes of chronic dacryocystitis-related corneal ulcers and to provide a basis for the rational clinical diagnosis and treatment.Methods:An observational case series study was performed.A total of 31 patients (31 eyes) diagnosed with chronic dacryocystitis-related corneal ulcers in Eye Hospital of Shandong First Medical University were enrolled from January 2016 to January 2020, with an average age of (53.0±10.8) years.The typical ocular signs, results of the etiological examination and microbial sensitivity test, treatment process and outcomes were analyzed.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.20191020-1).Written informed consent was obtained from each subject before any medical examination.Results:The average history of chronic dacryocystitis was (3.6±1.9) years.Corneal ulcers were mostly located in the peripheral cornea and had a rounded morphology with clear borders.The positive rate of corneal scraping was 74.2%(23/31), with bacteria in 19 eyes, fungal hyphae in 3 eyes, and both gram-positive cocci and fungal hyphae in 1 eye.The positive rate of microbial culture was 74.2%(23/31), with positive bacterial culture in 20 eyes (gram-positive cocci in 16 eyes and gram-negative bacilli in 4 eyes) and fungal growth in 3 eyes.The sensitivity rates of gram-positive cocci to vancomycin, rifampicin, moxifloxacin, and levofloxacin were 100%(16/16), 87.5%(14/16), 81.3%(13/16), and 75.0%(12/16), respectively.All patients were treated with surgery for chronic dacryocystitis, including 22 cases of endoscopic dacryocystorhinostomy, 7 cases of dacryocystectomy, and 2 cases of lacrimal duct probing combined with intubation.Among the 9 cases with an ulcer depth of <1/3 of the corneal thickness (CT), 6 cases were cured after (10.8±3.2) days of drug treatment and 3 cases underwent corneal lesion resection.The 6 patients with an ulcer depth of 1/3-2/3 of the CT underwent conjunctival flap covering surgery.Among the 16 patients with an ulcer depth of >2/3 of the CT, lamellar keratoplasty was performed in 6 cases, penetrating keratoplasty in 8 cases and evisceration in 2 cases with infectious endophthalmitis.Conclusions:Chronic dacryocystitis-related corneal ulcers are mainly located at the periphery of the cornea, and gram-positive cocci infections are the most common pathogenic bacteria.In patients with mild symptoms, corneal ulcers heal gradually after treatment with sensitive antibiotics.For patients with severe infections, appropriate surgery should be selected according to the depth of the corneal ulcer.

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