1.Construction and characterization of an infectious clone of an HIV-1 CRF01_AE isolate from China
Jingwan HAN ; Dijing JIA ; Shuai CHANG ; Hanping LI ; Yongjian LIU ; Lei JIA ; Xiaolin WANG ; Bohan ZHANG ; Jingyun LI ; Lin LI
Chinese Journal of Experimental and Clinical Virology 2025;39(5):556-564
Objective:To construct an infectious clone of a Chinese HIV-1 CRF01_AE epidemic strain with strong replication capacity,and comprehensively identify its viral phenotype and replication capacity.Methods:Using the CRF01_AE clinical isolate GX2005002,which was previously isolated from whole blood of an HIV-1-infected individual in China by our laboratory,as the parental strain,the full-length genome of the virus(9.7 kb)was divided into 5' half fragment(5.1 kb)and 3' half fragment(4.6 kb)for amplification. The proviral DNA was used as a template to amplify the virus genome,which was then ligated into the eukaryotic expression vector pEASY-T1. The consistency of its sequence with the parental strain sequence was identified through full-length genome sequencing and phylogenetic analysis. The replication capacity,syncytium inducibility,and cell tropism were experimentally identified to determine its phenotypic consistency with the parental strain.Results:An infectious clone of the CRF01_AE strain was successfully constructed,and its genome sequence exhibited high consistency with the sequence of the parental strain. By transfecting target cells,a derivative virus with infectious activity and replication capability was successfully rescued. The derived virus maintained phenotypic characteristics consistent with the parental strain,such as cell tropism and syncytium inducibility.Conclusion:This study successfully constructed an infectious clone of a Chinese HIV-1 CRF01_AE epidemic strain with clear background and distinct phenotype. The genomic sequence and viral phenotypic characteristics of the derived virus are basically consistent with the parental strain,providing strong representation of the original isolate and serving as a powerful tool for research on the correlation between the genetic characteristics,viral phenotype,and pathogenicity of HIV-1 CRF01_AE strains.
2.Value of Cardiac Magnetic Resonance Feature Tracking Technique in Evaluating Right Ventricle Function in Immune Checkpoint Inhibitor Induced Myocarditis
Peijun LIU ; Yining WANG ; Yi LI ; Lu LIN ; Xiao LI ; Yingxian LIU ; Hanping WANG ; Jian CAO ; Shihai ZHAO ; Jian WANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1400-1405
To investigate the clinical value of cardiac magnetic resonance feature tracking (CMR-FT) technology in the assessment of the right ventricle function in patients with immune checkpoint inhibitor (ICIs)-related myocarditis. Patients who visited Peking Union Medical College Hospital from April 2022 to April 2024, were diagnosed as ICIs-related myocarditis by cardiologists, and had normal right ventricular ejection fraction (RVEF) were enrolled in myocarditis group. Meanwhile, healthy individuals without cardiovascular diseases were selected as healthy control group. All subjects underwent cardiac magnetic resonance (CMR) examinations. Cardiac function parameters of the left and right ventricles were measured in the subjects, including left ventricular ejection fraction (LVEF), RVEF, left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI), right ventricular end-systolic volume index (RVESVI), and right ventricular end-diastolic volume index (RVEDVI). Additionally, myocardial strain of the left and right ventricles were recorded, encompassing left ventricular global longitudinal strain (LV-GLS), left ventricular global circumferential strain (LV-GCS), left ventricular global radial strain (LV-GRS), right ventricular global longitudinal strain (RV-GLS), right ventricular global circumferential strain (RV-GCS), and right ventricular global radial strain (RV-GRS). A total of 30 patients were induded in the myocarditis group and 20 in the healthy control group. The LVEF in the myocarditis group was was lower than that in the control group [(58.0±6.9)% Right ventricular myocardial strain obtained through CMR-FT technology can reveal early right ventricular cardiac dysfunction in patients with ICIs-related myocarditis, providing crucial evidence for early clinical prevention and timely intervention.
3.Comparison of the prognostic value of 15 nutritional/inflammatory indicators in postoperative cancer patients
Xiaoqian LIU ; Kai SUN ; Xiaolin WANG ; Qianqian ZHAO ; Xiaoxiao WU ; Fangqi SHEN ; Xi CHEN ; Chenxu TIAN ; Di WU ; Chunhua SONG ; HongXia XU ; Minghua CONG ; Hanping SHI ; Pingping JIA
Journal of Capital Medical University 2025;46(3):410-419
Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P<0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI<104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.
4.Renal insufficiency induced by anaplastic lymphoma kinase inhibitors
Haiting WU ; Hanping WANG ; Wei YE ; Xuemei LI ; Ke ZHENG
Adverse Drug Reactions Journal 2025;27(4):245-247
A 66-year-old female patient with lung adenocarcinoma was treated with crizotinib [the first-generation anaplastic lymphoma kinase (ALK) inhibitors] 250 mg twice daily. Prior to treatment, the patient's liver and kidney functions were normal. One month after treatment, her serum creatinine (Scr) was 85 μmol/L, and alanine aminotransferase (ALT) was 115 U/L. After discontinuing crizotinib for 10 days, both Scr and ALT returned to normal. One month later, the patient underwent a right lower lobectomy. Crizotinib was restarted postoperatively, and she developed symptoms of lower limb edema and poor appetite. After more than 3 months of treatment, her Scr increased to 129 μmol/L, ALT was 96 U/L, and aspartate aminotransferase (AST) was 83 U/L. Crizotinib was then switched to alectinib (the second-generation ALK inhibitors) 600 mg orally twice daily, and the patient's gastrointestinal symptoms and liver function were rapidly improved. However, her Scr continued to increase gradually (140-150 μmol/L). Renal biopsy pathology indicated IgA nephropathy and acute tubular injury. After 4 months of alectinib treatment, Scr was 174 μmol/L, and the drug was promptly discontinued. One month after discontinuation, Scr decreased to 125 μmol/L. Due to tumor progression, the patient restarted alectinib at a reduced dose (300 mg twice daily). Three months later, Scr increased to 177 μmol/L. Subsequently, alectinib was replaced with lorlatinib (the third-generation ALK inhibitors) 100 mg once daily due to tumor progression. After 6 months of treatment, the tumor condition was controlled, and Scr decreased to 124 μmol/L.
5.Comparison of the prognostic value of 15 nutritional/inflammatory indicators in postoperative cancer patients
Xiaoqian LIU ; Kai SUN ; Xiaolin WANG ; Qianqian ZHAO ; Xiaoxiao WU ; Fangqi SHEN ; Xi CHEN ; Chenxu TIAN ; Di WU ; Chunhua SONG ; HongXia XU ; Minghua CONG ; Hanping SHI ; Pingping JIA
Journal of Capital Medical University 2025;46(3):410-419
Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P<0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI<104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.
6.Renal insufficiency induced by anaplastic lymphoma kinase inhibitors
Haiting WU ; Hanping WANG ; Wei YE ; Xuemei LI ; Ke ZHENG
Adverse Drug Reactions Journal 2025;27(4):245-247
A 66-year-old female patient with lung adenocarcinoma was treated with crizotinib [the first-generation anaplastic lymphoma kinase (ALK) inhibitors] 250 mg twice daily. Prior to treatment, the patient's liver and kidney functions were normal. One month after treatment, her serum creatinine (Scr) was 85 μmol/L, and alanine aminotransferase (ALT) was 115 U/L. After discontinuing crizotinib for 10 days, both Scr and ALT returned to normal. One month later, the patient underwent a right lower lobectomy. Crizotinib was restarted postoperatively, and she developed symptoms of lower limb edema and poor appetite. After more than 3 months of treatment, her Scr increased to 129 μmol/L, ALT was 96 U/L, and aspartate aminotransferase (AST) was 83 U/L. Crizotinib was then switched to alectinib (the second-generation ALK inhibitors) 600 mg orally twice daily, and the patient's gastrointestinal symptoms and liver function were rapidly improved. However, her Scr continued to increase gradually (140-150 μmol/L). Renal biopsy pathology indicated IgA nephropathy and acute tubular injury. After 4 months of alectinib treatment, Scr was 174 μmol/L, and the drug was promptly discontinued. One month after discontinuation, Scr decreased to 125 μmol/L. Due to tumor progression, the patient restarted alectinib at a reduced dose (300 mg twice daily). Three months later, Scr increased to 177 μmol/L. Subsequently, alectinib was replaced with lorlatinib (the third-generation ALK inhibitors) 100 mg once daily due to tumor progression. After 6 months of treatment, the tumor condition was controlled, and Scr decreased to 124 μmol/L.
7.Construction and characterization of an infectious clone of an HIV-1 CRF01_AE isolate from China
Jingwan HAN ; Dijing JIA ; Shuai CHANG ; Hanping LI ; Yongjian LIU ; Lei JIA ; Xiaolin WANG ; Bohan ZHANG ; Jingyun LI ; Lin LI
Chinese Journal of Experimental and Clinical Virology 2025;39(5):556-564
Objective:To construct an infectious clone of a Chinese HIV-1 CRF01_AE epidemic strain with strong replication capacity,and comprehensively identify its viral phenotype and replication capacity.Methods:Using the CRF01_AE clinical isolate GX2005002,which was previously isolated from whole blood of an HIV-1-infected individual in China by our laboratory,as the parental strain,the full-length genome of the virus(9.7 kb)was divided into 5' half fragment(5.1 kb)and 3' half fragment(4.6 kb)for amplification. The proviral DNA was used as a template to amplify the virus genome,which was then ligated into the eukaryotic expression vector pEASY-T1. The consistency of its sequence with the parental strain sequence was identified through full-length genome sequencing and phylogenetic analysis. The replication capacity,syncytium inducibility,and cell tropism were experimentally identified to determine its phenotypic consistency with the parental strain.Results:An infectious clone of the CRF01_AE strain was successfully constructed,and its genome sequence exhibited high consistency with the sequence of the parental strain. By transfecting target cells,a derivative virus with infectious activity and replication capability was successfully rescued. The derived virus maintained phenotypic characteristics consistent with the parental strain,such as cell tropism and syncytium inducibility.Conclusion:This study successfully constructed an infectious clone of a Chinese HIV-1 CRF01_AE epidemic strain with clear background and distinct phenotype. The genomic sequence and viral phenotypic characteristics of the derived virus are basically consistent with the parental strain,providing strong representation of the original isolate and serving as a powerful tool for research on the correlation between the genetic characteristics,viral phenotype,and pathogenicity of HIV-1 CRF01_AE strains.
8.Effects of comprehensive moxibustion with Huolong cupping based on meridian theory in patients with lung-spleen qi deficiency type allergic rhinitis
Zhihui WANG ; Xiuhong LONG ; Liyun DING ; Fen LUO ; Hanping WEI ; Aihong MING ; Sihui LIN ; Yunfan YANG ; Tian FENG
Chinese Journal of Modern Nursing 2024;30(5):666-671
Objective:To explore the effect of comprehensive moxibustion with Huolong cupping in patients with lung-spleen qi deficiency type allergic rhinitis.Methods:This study was a randomized controlled trial. From October 2022 to April 2023, convenience sampling was used to select 66 patients with lung-spleen qi deficiency type allergic rhinitis who visited the Otolaryngology Head and Neck Clinic of Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine as the research subject. The patients were randomly divided into an experimental group ( n=33) and a control group ( n=33). Both groups received routine oral Chinese medicine treatment. On the basis of routine treatment, the experimental group performed comprehensive moxibustion with Huolong cupping on the meridians of the Du meridian and bladder meridian. This study compared the scores of Nasal Airway Resistance (NAR), Total Nasal Symptom Score (TNSS), Visual Analogue Scale (VAS), and Chinese version of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) between two groups of patients before and after intervention. Results:Eventually 30 patients in each of the experimental group and control group completed the study. After intervention, the NAR score of the experimental group was lower than that of the control group, and the difference was statistically significant ( P<0.05). Repeated measures analysis of variance showed that with the increase of treatment time, the TNSS, VAS, and RQLQ scores of the experimental group were lower than those of the control group with statistical differences ( P<0.05), and the time effect, inter group effect, and interaction effect were statistically significant ( P<0.05) . Conclusions:Huolong cupping comprehensive moxibustion can reduce nasal resistance, meliorate nasal symptoms and accompanying nasal symptoms, and improve the quality of life of patients.
9.Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer’s disease
Jiwei JIANG ; Yaou LIU ; Anxin WANG ; Zhizheng ZHUO ; Hanping SHI ; Xiaoli ZHANG ; Wenyi LI ; Mengfan SUN ; Shirui JIANG ; Yanli WANG ; Xinying ZOU ; Yuan ZHANG ; Ziyan JIA ; Jun XU
Chinese Medical Journal 2024;137(18):2202-2212
Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.
10.Isolation and cultivation of HIV strains circulating in China and the screening and identification of the standard strains
Siqi LI ; Guoxin ZHU ; Lin LI ; Jingyun LI ; Hanping LI ; Yongjian LIU ; Lei JIA ; Xiaolin WANG ; Tianyi LI ; Bohan ZHANG ; Jingwan HAN ; Chuntao MA
Chinese Journal of Experimental and Clinical Virology 2023;37(3):286-295
Objective:To screen the HIV standard strains with typical biological characteristics of HIV strains circulating in China through the isolation, culture, genotype and phenotype identification of HIV from the whole blood samples of HIV-infected persons, confirm genetic characteristics, traceability, and in line with the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023).Methods:Whole blood samples were collected from 48 HIV infected patients. Peripheral blood mononuclear cells (PBMCs) were isolated from the samples and co-cultured with PBMCs isolated from healthy persons′ whole blood samples to isolate and culture HIV from infected persons. We determined concentration of p24 antigen and the virus titer in the culture supernatant. The viral RNA was extracted from the successfully isolated strains, and the gag, pol genes and env C2V3 fragments of the viral genome were amplified and sequenced. The genotype, gene recombination and drug resistance sites were determined according to the viral gene sequences. Virus infection and replication were monitored by inoculating the virus culture supernatant into Ghost cells expressing CCR5 or CXCR4 to determine the viral tropism.The formation of syncytium was observed by inoculating the virus culture supernatant into MT-2 cells to determine whether was a syncytium-induced phenotype. Results:Fourteen strains with p24 antigen concentration > 1 ng/ml in culture supernatant were isolated and cultured from 48 fresh EDTA anticoagulated whole blood samples of HIV infected persons. Of the 14 strains, only one strain with a titer≥10 5 TCID 50/ml, 8 strains with titers ≥10 4 TCID 50/ml, and the other 5 strains with titers≥10 3 TCID 50/ml. Phylogenetic analysis showed that the genotypes of the strains were 9 strains of subtype B, 3 strains of CRF01_AE and 2 strains of CRF07_BC recombinant. Genotypic resistance analysis showed that 11 strains contained drug resistance sites. Ghost cells were used to verify the tropism of the strains, and it was found that 8 strains were CCR5 tropism, 6 strains were CXCR4 & CCR5 dual tropism. Only 2 of the 14 strains could induce MT-2 cytopathic effect, which was syncytium-inducing phenotype. Conclusions:Fourteen HIV strains with typical biological and genetic characteristics were isolated to screen the standard HIV strains. Among which, 1 strain was evaluated as a standard HIV strain that meets the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023). This study can also provide technical guidance for the screening of the HIV standard strains. Next step is to complete the application and reserve database construction according to the sharing mechanism of the HIV standard strains, to provide resources for the researches of HIV vaccines and drugs.

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