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Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

《医学前沿（英文）》 2022年 第16卷 第5期   页码 701-713 doi: 10.1007/s11684-022-0951-0

摘要： A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.

关键词： acquired resistance     EGFR inhibitor     apoptosis     lung cancer    

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lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired

《医学前沿（英文）》 2022年 第16卷 第3期   页码 389-402 doi: 10.1007/s11684-021-0856-3

摘要： Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2=0.033; P=0.018), followed by acute kidney injury (AKI; R2=0.032; P=0.011) and plasma MIP-1β level (R2=0.027; P=0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients’ lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

关键词： severe community-acquired pneumonia     lung microbiota     clinical improvements     7-category ordinal scale     Prevotellaceae    

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bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired

《医学前沿（英文）》 2021年 第15卷 第5期   页码 718-727 doi: 10.1007/s11684-020-0807-4

摘要： Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II–IV aGvHD, including two with grade III–IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

关键词： severe aplastic anemia     non-severe acquired aplastic anemia     haploidentical bone marrow transplantation     outcomes    

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Analysis of antibiotic usage for viral community-acquired pneumonia in adults

Rongmeng Jiang, Bing Han, Chang Dou, Fei Zhou, Bin Cao, Xingwang Li

《医学前沿（英文）》 2021年 第15卷 第1期   页码 139-143 doi: 10.1007/s11684-019-0736-2

摘要： The rationale for the antibiotic treatment of viral community-acquired pneumonia (CAP) in adults was analyzed to develop a clinical reference standard for this condition. Clinical data from 166 patients diagnosed with viral pneumonia across 14 hospitals in Beijing from November 2010 to December 2017 were collected. The indications for medications were evaluated, and the rationale for the use of antibiotics was analyzed. A total of 163 (98.3%) patients with viral pneumonia were treated with antibiotics. A combination of C-reactive protein (CRP) and procalcitonin (PCT) was used as markers to analyze the possible indications for antibiotic use. With threshold levels set at 0.25 µg/L for PCT and 20 mg/L for CRP, the rate of unreasonable use of antibiotics was 55.2%. By contrast, at a CRP level threshold of 60 mg/L, the rate of antibiotic misuse was 77.3%. A total of 39 of the 163 (23.9%) patients did not meet the guidelines for drug selection for viral CAP in adults. The unreasonable use of antibacterial drugs for the treatment of viral CAP in adults is a serious concern. Clinicians must reduce the unnecessary use of antibiotics.

关键词： adult     antibiotic     viral pneumonia    

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Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single

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《医学前沿（英文）》 2016年 第10卷 第4期   页码 430-436 doi: 10.1007/s11684-016-0492-5

摘要：

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 (range, 17 to 78) years with a female predominance (male:female ratio, 1:1.60). ADAMTS 13 activity were analyzed in 43 patients, among whom 33 (76.7%) patients had a baseline level of<5%. Mortality was 30%. Plasma exchange (PEX) was performed in 62 of 69 (89.9%) episodes. Corticosteroids were administered in 54 of 69 (78.3%) episodes. Other immunosuppressants (e.g., vincristine, cyclosporine, and cyclosporin) were used in 7 of 69 (10.1%) episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.

关键词： thrombotic thrombocytopenic purpura     ADAMTS 13     plasma exchange    

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Sudden death due to arrhythmogenic right ventricular cardiomyopathy: Two case reports

CHEN Xinshan, ZHANG Yigu, RAO Guangxun, HUANG Guangzhao

《医学前沿（英文）》 2007年 第1卷 第3期   页码 338-342 doi: 10.1007/s11684-007-0065-8

摘要： Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of primary myocardial disease characterized by the regional or global replacement of right ventricular myocardium by fatty and fibrolipomatous tissues. The ARVC, usually presenting with different clinical manifestations and pathological changes, were mainly seen in young men and is one of the main causes of sudden death in the young. Here two autopsied cases of Chinese men aged 30 and 23 years old who appeared healthy but died suddenly while at work are reported respectively. One of the victims had extensive and severe pathological changes in his heart involving the left ventricular wall as well as the ventricular septum and the right atrium. Not only was there a global fatty and fibrolipomatous tissue replacement of the right ventricular myocardia, but also mild sarcoplasmic coagulation in the myocardium and focal lymphocytic infiltration in the myocardial interstitium of the right ventricular wall. In addition, slight atherosclerosis of the coronary artery and intimal thickening of the sino-atrial node were observed. It is believed that there are no marked differences in the pathological changes of ARVC between Chinese patients and patients from western countries. The etiology and pathogenesis of ARVC could not be explained by a single cause or factor and they are probably related to various congenital and acquired causes or factors.

关键词： sarcoplasmic coagulation     acquired     ventricular myocardium     sino-atrial     autopsied    

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Study on factors affecting TB/HIV co-infection in four counties of China

Shi-Ming CHENG MD, Yu-Ji LAI MS, Er-Yong LIU MS, Lin ZHOU MD, Xue-Jing WANG MS, Qiu-Lan CHEN MS, Dong-Ming LI MS, Ning WANG MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 185-191 doi: 10.1007/s11684-010-0040-7

摘要： The factors affecting case detection of tuberculosis (TB)/human immunodeficiency virus (HIV) co-infection cases were explored in order to provide evidence-based formulation of a TB/HIV co-infection control strategy in China. Four counties with different modes of HIV transmission and varying cooperation mechanisms between TB and HIV institutions were selected. HIV test among TB patients and TB examination among people living with HIV/acquired immunodeficiency syndrome (AIDS) were conducted. Patients also completed questionnaires on potential factors affecting TB/HIV co-infection. The results showed that 19 (1.7%) were HIV-positive among 1089 cases of people living with active TB who received HIV testing. Conversely, there were 126 (10%) cases of active TB among 1255 cases of people living with HIV/AIDS. Among the newly discovered 145 cases of TB/HIV co-infection, AIDS institutions found 86.9% of these co-infections and 14.1% came from TB institutes. In different registration categories, there were 31 (21.4%) cases of smear positive TB, 104 (71.7%) cases of smear negative TB, and extrapulmonary cases accounted for 10 (6.9%). Gender, occupation, marital status, ethnic group, education, HIV transmission route, CD4 level, and type of TB susceptible symptoms had significant effects on whether HIV/AIDS patients were co-infected with TB disease (<0.01). Sex, age, ethnic group, occupation, and type of tuberculosis had no significant influence on whether TB patients had HIV infection. AIDS institutions could find more TB/HIV co-infection patients in comparison with TB institutions, particularly in patients with smear negative pulmonary tuberculosis and extrapulmonary tuberculosis. Therefore, a cooperation mechanism should be built up between TB and HIV control systems, and routine TB checks should be conducted for HIV/AIDS patients. In areas where sex or drug use is the major transmission mode of HIV infection, antiretroviral therapy should be expanded, treatment adherence should be improved and patients’ immunity level should be increased in order to decrease TB incidence. Cough and expectoration of more than two weeks, bloody sputum, and recurrent fevers could be revealing symptoms in TB screening of HIV/AIDS patients.

关键词： tuberculosis/acquired immunodeficiency syndrome     dual infection     prevention and control     case detection     impact factors    

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Co-infection of HIV and parasites in China: Results from an epidemiological survey in rural areas of Fuyang city, Anhui province, China

Li-Guang TIAN MPH, Jia-Xu CHEN PhD, Yu-Chun CAI BM, Jian GUO MPH, Xiao-Mei TONG, Qin LIU DVM, Xiao-Nong ZHOU PhD, Tian-Ping WANG PhD, Xiao-Mei YIN, Wei-Duo WU, Li ZHOU, Feng-Feng WANG, Zhen-Li WANG MSc, Guo-Jin CHENG, Peter STEINMANN PhD, Lan-Hua LI MSc,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 192-198 doi: 10.1007/s11684-010-0039-0

摘要： The aim of this study was to investigate epidemiological characteristics of co-infection of HIV and intestinal parasites in a HIV/AIDS highly endemic area in China. A cross-sectional survey was carried out in two villages where HIV/AIDS prevalence in residents was over 1%. Stool samples of all residents in the two targeted villages were examined for the presence of intestinal parasites. Blood examination was performed for the HIV infection detection and anemia test. A questionnaire survey was carried out in all residents participating in the study. A total of 769 individuals were enrolled in the investigation, 720 of whom were involved in stool examination of intestinal parasites. The infection rates of parasites in the residents of the targeted villages were as follows: 0.56% for , 4.03% for Hookworm, 0.28% for , 0.42% for , 21.39% for , 3.89% for , 1.67% for spp., 4.44% for spp., and no infection for . The overall infection rate of intestinal worms was 4.72%, intestinal parasite infection rate was 24.31%, the anemia prevalence rate was 34.68%, the co-infection rate of HIV and intestinal helminthes 2.17%, the co-infection rate of HIV and intestinal protozoa 28.26%, of which the co-infection rates of HIV and , and HIV and spp. were 19.57% and 13.04%, respectively. A significant difference of spp. infection rate was found between HIV-positive group (13.04%) and HIV-negative group (4.70%) (<0.05). Higher prevalence of anemia (34.68%) occurred in the study villages, particularly in children (>50%) and women (>39%). It was concluded that the infection rate of intestinal protozoa in the residents was higher than that of intestinal helminthes in the local setting, and a same pattern appeared in the co-infection rate of HIV and parasites. An interesting finding is that the infection rate of spp. among the HIV-positives was significantly higher than that in the HIV-negatives, and children and women had higher anemia prevalence.

关键词： human immunodeficiency virus (HIV)     acquired immunodeficiency syndrome (AIDS)     co-infection     intestinal parasites     helminthes     protozoa     China    

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标题 作者 时间 类型 操作

Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

期刊论文

lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired

期刊论文

bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired

期刊论文

Analysis of antibiotic usage for viral community-acquired pneumonia in adults

Rongmeng Jiang, Bing Han, Chang Dou, Fei Zhou, Bin Cao, Xingwang Li

期刊论文

Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single

null

期刊论文

Sudden death due to arrhythmogenic right ventricular cardiomyopathy: Two case reports

CHEN Xinshan, ZHANG Yigu, RAO Guangxun, HUANG Guangzhao

期刊论文

Study on factors affecting TB/HIV co-infection in four counties of China

Shi-Ming CHENG MD, Yu-Ji LAI MS, Er-Yong LIU MS, Lin ZHOU MD, Xue-Jing WANG MS, Qiu-Lan CHEN MS, Dong-Ming LI MS, Ning WANG MD,

期刊论文

Co-infection of HIV and parasites in China: Results from an epidemiological survey in rural areas of Fuyang city, Anhui province, China

Li-Guang TIAN MPH, Jia-Xu CHEN PhD, Yu-Chun CAI BM, Jian GUO MPH, Xiao-Mei TONG, Qin LIU DVM, Xiao-Nong ZHOU PhD, Tian-Ping WANG PhD, Xiao-Mei YIN, Wei-Duo WU, Li ZHOU, Feng-Feng WANG, Zhen-Li WANG MSc, Guo-Jin CHENG, Peter STEINMANN PhD, Lan-Hua LI MSc,

期刊论文