Ceritinib as First-line Treatment for Advanced Lung Adenocarcinoma with COX7A2L-ALK Fusion: A Case Report and Literature Review / 中国肺癌杂志

Lung cancer is the most common in incidence and mortality worldwide. With the development of next generation sequencing (NGS) detection technology, more and more patients with rare anaplastic lymphoma kinase (ALK) fusion mutations were detected. A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors. The best response of the patient was assessed as partial response (PR) with Ceritinib treatment. By literature review, 22 cases of rare ALK fusion were reported in 19 articles. Combined with this case, 23 cases were analyzed. The objective response rate (ORR) was 82.6% (19/23) and disease control rate (DCR) was 95.7% (22/23) for rare ALK fusions patients treated with ALK inhibitors. Lung adenocarcinoma patients with rare ALK fusion could benefit from ALK inhibitors.
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Preparation and Application of Monoclonal Antibody Against Human von Willebrand Factor Propeptide / 中国实验血液学杂志

OBJECTIVE@#To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody.@*METHODS@#The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected.@*RESULTS@#Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation.@*CONCLUSION@#Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.

Challenges and countermeasures on the translation of scientific research achievements of public hospitals in China / 中华医院管理杂志

Public hospitals play an important role in independent innovation of basic medicine and clinical medicine. As key players in translation of medical research achievements, they play a pivotal role in promoting the development of medical sciences. At present, these hospitals however, are faced with challenges in the translation, namely system defects, unclear property rights ownership, misleading research project goals, defective assessment mechanism, insufficient funding, and lack of translation channels. In such considerations, the authors suggested based on their experiences to improve the translation system of scientific research achievements, set up special departments for translation, clarify the rights to use and dispose of scientific research achievements and that to yields. They also proposed to actively guide the establishment of clinical application projects, improve the evaluation mechanism, and broaden channels of funding. These measures are expected to accelerate the translation of scientific research achievements.

Levosimendan does not reduce the mortality of critically ill adult patients with sepsis and septic shock: a meta-analysis / 中华医学杂志(英文版)

Background:@#Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and septic shock have been inconsistent. We aimed to provide an updated analysis of the therapeutic value of levosimendan in adult patients with sepsis and septic shock, in order to provide evidence-based medical evidence for its use.@*Methods:@#PubMed, Embase, Cochrane Library, Wanfang Data, and CNKI were searched until August 2018 without language restriction. Randomized controlled studies of levosimendan with either inotropic drugs or placebo for the treatment of sepsis or septic shock were enrolled. The primary outcome was mortality, and cardiac index and serum lactate levels were the secondary outcomes.@*Results:@#A total of 20 randomized controlled studies were included in this meta-analysis, including 1467 patients, with 738 patients in the experimental group (levosimendan group) and 729 patients in the control group (other inotropic drugs or placebo). There were no significant differences in mortality between the levosimendan and control groups (fixed-effect relative risk [RR] = 0.90, 95% confidence interval [CI] [0.79, 1.03], P = 0.13). Levosimendan increased the cardiac index (VMD [weighted mean difference] = 0.51, 95% CI [0.06, 0.95], P = 0.02); and serum lactate levels were lower (VMD = -1.04, 95% CI [-1.47, -0.60], P < 0.00001).@*Conclusions:@#Based on current clinical evidence, levosimendan does not reduce mortality in adult critically ill patients with sepsis and septic shock. Physicians should use levosimendan with caution in patients with sepsis and septic shock.

Visualization Analysis of Domestic Drug Centralized Procurement Study from 2000 to Jun. 2018 / 中国药房

OBJECTIVE： To explore the situation and research hotspots of drug centralized procurement study， and to find existing problems in the development of this field so as to provide reference for further improving drug centralized procurement in China. METHODS： The literatures were retrieved from CNKI， Wanfang and VIP database during 2000-Jun. 2018. CiteSpace software， which was a visualization software， was used to analyze statistically the publication time， author， research institution and keywords. RESULTS： A total of 3 455 literatures were included in the study. The number of literatures in this field had increased significantly since 2009. The author and institution cooperation network were scattered relatively. The research teams were mainly universities and research institutes， few of which were public hospitals. Before 2009，the scholars focused on feasibility analysis of the implementation of drug centralized procurement policy in China， analysis of centralized drug procurement system and model introduction. After New Medical Reform in 2009， great importance was attached to effect evaluation of essential medicine centralized procurement and rational drug use in public hospital. In recent year， the latest outbreak of the keywords were “drug pricing reform”“price negotiation”“medical insurance payment”“drug shortage”“tripartite linkage of medical institutions”“drug purchasing with quantity”“supply guarantee” and so on， which were the newest research hotspots.  CONCLUSIONS： The research focus of drug centralized procurement is changing with the adjustment of national policy. At present， the focus of research in this field has shifted to the research on the mode and situation of drug purchasing with quantity， the reform of medical insurance payment standard， the negotiation of drug price in public hospitals and the reform of drug price. Under the background of “Tripartite Linkage of Medical Institutions”， the strategy of drug supply guarantee system was improved， and the countermeasures are explored to alleviate drug shortage and irrational drug use. In the future， cooperation and academic exchanges should be strengthened in this field so as to make the multi-center and multi-disciplinary cooperation mode should become the mainstream. At the same time， public hospitals should enhance their main position and actively participate in research on related topics， so as to promote to establish and improve the drug supply guarantee system and reduce the medical burden of the public.

Levosimendan does not reduce the mortality of critically ill adult patients with sepsis and septic shock: a meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and septic shock have been inconsistent. We aimed to provide an updated analysis of the therapeutic value of levosimendan in adult patients with sepsis and septic shock, in order to provide evidence-based medical evidence for its use.@*METHODS@#PubMed, Embase, Cochrane Library, Wanfang Data, and CNKI were searched until August 2018 without language restriction. Randomized controlled studies of levosimendan with either inotropic drugs or placebo for the treatment of sepsis or septic shock were enrolled. The primary outcome was mortality, and cardiac index and serum lactate levels were the secondary outcomes.@*RESULTS@#A total of 20 randomized controlled studies were included in this meta-analysis, including 1467 patients, with 738 patients in the experimental group (levosimendan group) and 729 patients in the control group (other inotropic drugs or placebo). There were no significant differences in mortality between the levosimendan and control groups (fixed-effect relative risk [RR] = 0.90, 95% confidence interval [CI] [0.79, 1.03], P = 0.13). Levosimendan increased the cardiac index (VMD [weighted mean difference] = 0.51, 95% CI [0.06, 0.95], P = 0.02); and serum lactate levels were lower (VMD = -1.04, 95% CI [-1.47, -0.60], P < 0.00001).@*CONCLUSIONS@#Based on current clinical evidence, levosimendan does not reduce mortality in adult critically ill patients with sepsis and septic shock. Physicians should use levosimendan with caution in patients with sepsis and septic shock.

Analysis of blood lipid characteristics and related factors in early childhood systemic lupus erythematosus / 中华风湿病学杂志

Objective To explore the characteristics of lipid profile in children with systemic lupus erythematosus (SLE) and its risk factors.Methods A total of 225 untreated children with SLE were enrolled in this study.According to the values of low-density lipoprotein cholesterol (LDL-C),very low density lipoprotein cholesterol (VLDL-C),high-density lipoprotein cholesterol (HDL-C),totalglycerin (TG) and triglyceride (TG),they were grouped into LDL-C normal group and elevated group,VLDL-C normal group and elevated group,HDL-C normal group and lower group,TG normal group and elevated group,TC normal group and elevated group.We used x2 test,binary logistic regression and t-test to analyze the relationship between various lipid groups and clinical symptoms,laboratory tests,disease activity,hormones and complications.Results One hundred and eighty-five cases (82.22％) of children with SLE developed dyslipidemia,mainly manifested as increased LDL-C,VLDL-C,TG,TC levelsand decreased HDL-C level.There was a positive correlation between urea nitrogen and TG (r=0.257,P＜0.01),positive correlation with LDL-C (r=0.129,P＜0.05)and positive correlation with VLDL-C (r=0.225,P＜0.01).Albumin and TG (r=-0.464,P＜0.01),TC (r=-0.246,P＜0.01),LDL-C (r=-0.138,P＜0.05),VLDL-C (r=-0.426,P＜0.05) were negatively correlated.Urine protein level (2 h) was positively correlated with TG (r=0.257,P＜0.01).Systemic lupus erythematosus disease activity index (SLEDAI) was positively correlated with TG (r=0.597,P＜0.01),positively correlated with VLDL-C (r=0.565,P＜0.01) and negatively correlated with HDL-C (r=-0.324,P＜0.01).Complement C3 was negatively correlated with TG (r=-0.284,P＜0.01).The positive proportion of anti-dsDNA antibody [TG-increased group (58/89) was higher than TG normal group (70/136) (x2=4.1 16,P=0.042);TC normal group (112/186) was higher than TC-increased group (16/39) (x2=4.841,P=0.028);LDL-C elevated group (7/21) was higher than LDL-C normal group (121/204) (x2=5.240,P=0.022)].The proportion of coronary involvement events in the TG increased group (25/89) was higher than that in the TG positive group (17/136) (x2=8.612,P=0.003).The proportion of LN was higher in each dyslipidemia group [TG increased group (54/89) was higher than TG normal group (34/136) (x2=28.75,P＜0.01);TC increased group (23/39) was higher than TC normal group (65/186)(x2=7.816,P=0.005);LDL-C elevated group (14/21) was higher than LDL-C normal group (75/204) (x2=7,385,P=0.007);VLDL-C elevated group (12/17) was higher than the VLDL-C normal group (76/208) (x2=7.651,P=0.006)] (P＜0.05).Conclusion Children with SLE have significant dyslipidemia.A variety of factors are involved in children with SLE dyslipidemia.Dyslipidemia can cause multiple organ damage in children with SLE.

Comparison of effects between IL-2 and IL-7 on glutamic acid decarboxylase 65 reactive T cell responses in patients with Type Ⅰ diabetes / 中南大学学报(医学版)

Objective:To explore the type of cytokine (IL-2 or IL-7) and its most optimal concentration regarding the improvement of the signal-to-noise ratio of glutamic acid decarboxylase 65 (GAD65) in enzyme-linked immunospot (ELISPOT) assay in Type 1 diabetic (T1DM) patients.Methods:Twenty T1DM patients (Group A) and sixteen healthy controls matched with age and sex (Group B) were enrolled in our study,and their peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method.GAD65,internal control and Pediacel served as "five-for-one" vaccine were selected as the stimulating antigen.Different concentrations of IL-2 [0 U/mL (Group 1),0.5 U/mL (Group 2),2.5 U/mL (Group 3) and 12.5 U/mL (Group 4)] were added to the culture system.The CD4+ T cells of secreting interferon-gamma (IFN-γ) in the above groups were determined by ELISPOT.The spots number,net values and stimulating index (SI) were compared in GAD65 (signal) and internal control (background).Next,another 21 T1DM patients (Group C) and 12 healthy controls matched with age and sex (Group D) were enrolled,and the specific T cell response to the GAD65 antigen was detected.The net values and SI were compared between the best optimal concentration of IL-2 (2.5 U/mL,Group 5) and IL-7 (0.5 ng/mL,Group 6).Results:1) After adding IL-2 into the Group A,the amount of GAD65 reactive T cells in different groups increased compared with Group A1,while the background in the internal control also increased gradually with the increased concentration of IL-2.There was no significant difference in net value (signal-noise) in the different concentration between the Group A3 and the Group A4 (P＞0.05).The SI in the Group A3 (2.8),the highest one,was significantly higher than that in the Group B3 (1.3) (P＜0.05).2) Although the number of GAD65 spots in the Group C6 and the Group D6 were slightly higher than that in the Group C5 and the Group D5,respectively,the background in the Group C6 and the Group D6 also increased,without statistical significance (P＞0.05).The mean net value spot and SI in the Group C5 (net value:5.5;SI:2.8) were both significantly higher than those in the Group C6 (net value:4.3;SI:1.8) (bothP9＜0.05).Conclusion:The concentration of 2.5 U/mL for IL-2 is proved to be the best optimal concentration for GAD65 specific T-cell responses in ELISPOT in patients with T1DM.IL-2 is much better than IL-7 in improvement of the SI in the ELISPOT.

The short-term effects of particulate matter on lung function of college students in autumn and winter in Wuhan / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of indoor and outdoor PM2.5 (fine particulate matter, particulate matter with an aerodynamic diameter ≤ 2.5 µm) on lung function of college students in autumn and winter in Wuhan.</p><p><b>METHODS</b>In this panel study, 37 college students (excluded subject of respiratory disease and smoking history) aged 19 - 21 were investigated by cluster sampling in a university in Wuhan. The follow-up study lasted for 28 days in total, including two study periods, Oct. 29 to Nov. 11, 2009 (autumn) and Dec. 23, 2009 to Jan.5, 2010 (winter), the peak expiratory flow (PEF) of the college students were measured daily in the morning and evening in the university. PM10 and PM2.5 were monitored indoors and outdoors. The effects of PM on lung function of college students were analyzed by using generalized estimating equation (GEE).</p><p><b>RESULTS</b>Average daily concentrations of indoor, outdoor PM2.5 in autumn were (91.3 ± 43.7) and (104.2 ± 49.4) µg/m(3) respectively, while in winter the concentrations of indoor and outdoor PM2.5 were (110.6 ± 42.3) and (143.5 ± 51.2) µg/m(3). The single pollutant model showed that in winter, the evening PEF decrement was significantly associated with increasing outdoor PM2.5. With an increase of 10 µg/m(3) outdoor PM2.5, the PEF measured in the evening decreased 1.27 L/min (95%CI: 0.02 - 2.52 L/min, respectively). Meanwhile, the results showed that 2-days lagged outdoor PM2.5 was also significantly associated with morning PEF. An increase of 10 µg/m(3) 2-days lagged outdoor PM2.5 caused the decrease of 1.82 L/min (95%CI: -3.53 - -0.11 L/min) of PEF measured in the morning. Controlling the influence of gaseous pollutants and building the two pollutants models, the results indicated that no significant changes of PEF of students being exposed to PM2.5 on same day (lag 0) were observed. However, under consideration of SO2 effect, significant association between an increase of 10 µg/m(3) 2-days lagged outdoor PM2.5 and changes of morning PEF (-1.81 L/min, 95%CI: -3.51 - -0.11 L/min, P = 0.037) was found. The relationship between changes of concentrations and PEF was not observed in autumn in this study.</p><p><b>CONCLUSION</b>In our panel study, exposure to outdoor PM2.5 is significantly associated with PEF among college students in winter, but not in autumn.</p>

Pulsed-field gel electrophoresis typing on non-O157 Shiga toxin-producing Escherichia coli isolates / 中华流行病学杂志

<p><b>OBJECTIVE</b>To establish a database and to understand the molecular epidemiological features of non-O157 Shiga toxin-producing Escherichia coli (STEC) isolates from different animal reservoirs and patients.</p><p><b>METHODS</b>Pulsed-field gel electrophoresis (PFGE) was performed according to the PulseNet protocol with minor modifications. A dendrogram was constructed using the BioNumerics.</p><p><b>RESULTS</b>Under the PulseNet protocol, 62 PFGE patterns were obtained from 76 non-O157 STEC isolates and then divided into A to M groups. Isolates from different sources were widely distributed in different groups, but were predominant seen in certain groups.</p><p><b>CONCLUSION</b>The non-O157 STEC isolates in China were highly polymorphic. PulseNet protocol seemed to be suitable for the typing of Chinese non-O157 STEC isolates.</p>

Effect of repetitive transcranial magnetic stimulation on serum brain derived neurotrophic factor in depressive patients / 中华行为医学与脑科学杂志

Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS) treatment on the brain derived neurotrophic factor(BDNF) serum levels in depressive patients.Methods Sixty-eight unipolar depressions treated with venlafaxine were randomly assigned to the real rTMS group(n =34)and the sham rTMS group(n =34),which were accepted the real or the shame rTMS treatment on the left dorsolateral prefrontal lobes respectively.The Hamilton Rating Scale for Depression (HAMD) and BDNF serum was assayed before and after 4 weeks' treatment.Results 1) A significant increase of serum BDNF((12.2 ± 1.3) μg/L vs (5.6 ± 0.8) μg/L,t=-9.167,P=0.000;(11.4 ± 1.5)μg/L vs (6.0± 1.0)μg/L,t=-7.421,P=0.000)and a significant decline of HAMD((11.6 ± 1.7) score vs (32.6 ± 2.5) score,t =14.654,P =0.000 ; (4.2 ± 2.8) score vs (31.8 ± 3.2)score,t=12.089,P =0.000) were found after the treatment in the real and the shame group,and the real group changed more significantly than the shame group ((6.7 ± 0.8) μg/L vs (5.1 ± l.2) μg/L,t =2.690,P =0.009 ; (21.0 ± 2.1) score vs (17.6 ± 2.6) score,t =2.693,P =0.000).2) A negative correlation was found between the serum BDNF levels and the HAM D scores before the treatment(r =-0.530,P=0.003; r =-0.490,P =0.004),and a positive correlation between changes of BDNF levels and HAMD scores changes(r =0.439,P =0.006 ; r =0.454,P =0.005).Conclusion The rTMS treatment can increase serum BDNF levels in depressive patients.