In vitro interaction of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen in the asexual blood stage of Plasmodium falciparum 3D7.

Naphthoquine is a promising candidate for antimalarial combination therapy. Its combination with artemisinin has demonstrated excellent efficacy in clinical trials conducted across various malaria-endemic areas. A co-formulated combination of naphthoquine and azithromycin has also shown high clinical efficacy for malaria prophylaxis in Southeast Asia. Developing new combination therapies using naphthoquine will provide additional arsenal responses to the growing threat of artemisinin resistance. Furthermore, due to its long half-life, the possible interaction of naphthoquine with other drugs also needs attention. However, studies on its pharmacodynamic interactions with other drugs are still limited. In this study, the in vitro interactions of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen were evaluated in the asexual stage of Plasmodium falciparum 3D7. By using the combination index analysis and the SYBR Green I-based fluorescence assay, different interaction patterns of selected drugs with naphthoquine were revealed. Curcumin showed a slight but significant synergistic interaction with naphthoquine at lower effect levels, and no antagonism was observed across the full range of effect levels for all tested ratios. Atovaquone showed a potency decline when combined with naphthoquine. For ivermectin, a significant antagonism with naphthoquine was observed at a broad range of effect levels below 75% inhibition, although no significant interaction was observed at higher effect levels. Ketotifen interacted with naphthoquine similar to ivermectin, but significant antagonism was observed for only one tested ratio. These findings should be helpful to the development of new naphthoquine-based combination therapy and the clinically reasonable application of naphthoquine-containing therapies. IMPORTANCE: Pharmacodynamic interaction between antimalarials is not only crucial for the development of new antimalarial combination therapies but also important for the appropriate clinical use of antimalarials. The significant synergism between curcumin and naphthoquine observed in this study suggests the potential value for further development of new antimalarial combination therapy. The finding of a decline in atovaquone potency in the presence of naphthoquine alerts to a possible risk of treatment or prophylaxis failure for atovaquone-proguanil following naphthoquine-containing therapies. The observation of antagonism between naphthoquine and ivermectin raised a need for concern about the applicability of naphthoquine-containing therapy in malaria-endemic areas with ivermectin mass drug administration deployed. Considering the role of atovaquone-proguanil as a major alternative when first-line artemisinin-based combination therapy is ineffective and the wide implementation of ivermectin mass drug administration in malaria-endemic countries, the above findings will be important for the appropriate clinical application of antimalarials involving naphthoquine-containing therapies.

Disulfide-incorporated lipid prodrugs of cidofovir: Synthesis, antiviral activity, and release mechanism.

The double-stranded DNA (dsDNA) viruses represented by adenovirus and monkeypox virus, have attracted widespread attention due to their high infectivity. In 2022, the global outbreak of mpox (or monkeypox) has led to the declaration of a Public Health Emergency of International Concern. However, to date therapeutics approved for dsDNA virus infections remain limited and there are still no available treatments for some of these diseases. The development of new therapies for treating dsDNA infection is in urgent need. In this study, we designed and synthesized a series of novel disulfide-incorporated lipid conjugates of cidofovir (CDV) as potential candidates against dsDNA viruses including vaccinia virus (VACV) and adenovirus (AdV) 5. The structure-activity relationship analyses revealed that the optimum linker moiety was C2H4 and the optimum aliphatic chain length was 18 or 20 atoms. Among the synthesized conjugates, 1c exhibited more potency against VACV (IC50 = 0.0960 µM in Vero cells; IC50 = 0.0790 µM in A549 cells) and AdV5 (IC50 = 0.1572 µM in A549 cells) than brincidofovir (BCV). The transmission electron microscopy (TEM) images revealed that the conjugates could form micelles in phosphate buffer. The stability studies in the GSH environment demonstrated that the formation of micelles in phosphate buffer might protect the disulfide bond from glutathione (GSH) reduction. The dominant means of the synthetic conjugates to liberate the parent drug CDV was by enzymatic hydrolysis. Furthermore, the synthetic conjugates remained sufficiently stable in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and pooled human plasma, which indicated the possibility for oral administration. These results indicated 1c may be a broad-spectrum antiviral candidate against dsDNA viruses with potential oral administration. Moreover, modification of the aliphatic chain attached to the nucleoside phosphonate group was involved as an efficient prodrug strategy for the development of potent antiviral candidates.

Orthogonal dual reporter-based gain-of-signal assay for probing SARS-CoV-2 3CL protease activity in living cells: inhibitor identification and mutation investigation.

ABSTRACTThe main protease (3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2 has become a focus of anti-coronavirus research. Despite efforts, drug development targeting 3CLpro has been hampered by limitations in the currently available activity assays. Additionally, the emergence of 3CLpro mutations in circulating SARS-CoV-2 variants has raised concerns about potential resistance. Both emphasize the need for a more reliable, sensitive, and facile 3CLpro assay. Here, we report an orthogonal dual reporter-based gain-of-signal assay for measuring 3CLpro activity in living cells. It builds on the finding that 3CLpro induces cytotoxicity and reporter expression suppression, which can be rescued by its inhibitor or mutation. This assay circumvents most limitations in previously reported assays, especially false positives caused by nonspecific compounds and signal interference from test compounds. It is also convenient and robust for high throughput screening of compounds and comparing the drug susceptibilities of mutants. Using this assay, we screened 1789 compounds, including natural products and protease inhibitors, with 45 compounds that have been reported to inhibit SARS-CoV-2 3CLpro among them. Except for the approved drug PF-07321332, only five of these inhibit 3CLpro in our assays: GC376; PF-00835231; S-217622; Boceprevir; and Z-FA-FMK. The susceptibilities of seven 3CLpro mutants prevalent in circulating variants to PF-07321332, S-217622, and GC376 were also assessed. Three mutants were identified as being less susceptible to PF-07321322 (P132H) and S-217622 (G15S, T21I). This assay should greatly facilitate the development of novel 3CLpro-targeted drugs and the monitoring of the susceptibility of emerging SARS-CoV-2 variants to 3CLpro inhibitors.

Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

Selection and application of implementation strategies in implementation research / 中华预防医学杂志

Implementation research is a discipline that attempts to promote the application of evidence-based interventions in different settings and populations by using various methods and measures. Implementation strategies are the central part of implementation research, and as the field of implementation science evolves, more and more implementation strategies have been developed to facilitate the application of evidence-based interventions in the real world. To help researchers better understand and apply implementation strategies, this study will introduce implementation strategies in three aspects: classification, selection and application, and report.

The role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes / 中华预防医学杂志

Objective: To investigate the role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes. Methods: Based on a prospective cohort study, singleton live births and their mothers from the Ma'anshan Birth Cohort Study (MABC) were included as participants in this study. The maternal pregnancy-related anxiety symptoms in the third trimester of pregnancy were evaluated by using the Pregnancy-related Anxiety Questionnaire. The neonatal birth outcomes were collected from medical records. The placental tissues from 300 pregnant women with pregnancy-related anxiety and 300 without pregnancy-related anxiety were collected to detect the methylation of FKBP5, NR3C1 and HSD11B2 genes using the Methyl Target approach. The methylation factors were extracted by exploratory factor analysis. Linear regression or logistic regression models were used to analyze the association between pregnancy-related anxiety in the third trimester, methylation factor scores, and birth outcomes. The mediating role of methylation factors in the association between pregnancy-related anxiety in the third trimester and birth outcomes was analyzed by using the Process procedure. Results: The mean age of 2 833 pregnant women was (26.60±3.60) years old. After adjusting for confounding factors, pregnancy-related anxiety in the third trimester increased the risk of small-for-gestational-age (OR=1.32, 95%CI:1.00-1.74). A total of 5 methylation factors were extracted, and the factor 5 was loaded with FKBP5 CpGs 18-21. Pregnancy-related anxiety in the third trimester was negatively correlated with the factor 5 (β=-0.24,95%CI:-0.44--0.05). The factor 5 was positively correlated with the gestational age (β=0.17, 95%CI:0.06-0.27). In addition, the factor 2 (β=0.02,95%CI:0.00-0.04) and factor 3 (β=0.03,95%CI:0.01-0.05) were positively correlated with 5-min Apgar score after delivery. However, this study did not found the mediating role of the scores of the factor characterized by FKBP5 in the relationship between pregnancy-related anxiety and birth outcomes. Conclusion: Pregnancy-related anxiety in the third trimester may reduce the methylation level of FKBP5 CpGs 18-21 in placental tissues and is associated with the risk of small-for-gestational-age.

Impact of Tobacco Smoking on Health Care Utilization and Medical Costs in Chronic Obstructive Pulmonary Disease, Coronary Heart Disease and Diabetes.

OBJECTIVE: To determine the impact of smoking on disease-specific health care utilization and medical costs in patients with chronic non-communicable diseases (NCDs). METHODS: Participants were middle-aged and elderly adults with chronic NCDs from a prospective cohort in China. Logistic regressions and linear models were used to assess the relationship between tobacco smoking, health care utilization and medical costs. RESULTS: Totally, 1020 patients with chronic obstructive pulmonary disease (COPD), 3144 patients with coronary heart disease (CHD), and 1405 patients with diabetes were included in the analysis. Among patients with COPD, current smokers (ß: 0.030, 95% CI: -0.032-0.092) and former smokers (ß: 0.072, 95% CI: 0.014-0.131) had 3.0% and 7.2% higher total medical costs than never smokers. Medical costs of patients who had smoked for 21-40 years (ß: 0.028, 95% CI:-0.038-0.094) and ≥41 years (ß: 0.053, 95% CI: -0.004ß0.110) were higher than those of never smokers. Patients who smoked ≥21 cigarettes (ß: 0.145, 95% CI: 0.051-0.239) per day had more inpatient visits than never smokers. The association between smoking and health care utilization and medical costs in people with CHD group was similar to that in people with COPD; however, there were no significant associations in people with diabetes. CONCLUSION: This study reveals that the impact of smoking on health care utilization and medical costs varies among patients with COPD, CHD, and diabetes. Tobacco control might be more effective at reducing the burden of disease for patients with COPD and CHD than for patients with diabetes.

Expression level and function of MEX3A in non-small cell lung cancer / 中国肿瘤临床

Objective: To investigate the expression of MEX3A in non-small cell lung cancer (NSCLC) cells and the effects of MEX3A knockout on cell cycle, proliferation, invasion, migration, and apoptosis. Methods: We screened out MEX3A, which was significantly highly expressed, by mRNA microarray and The Cancer Genome Atlas (TCGA) database information analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of MEX3A in NSCLC cells. A549 and NCI-H292 cells showed high expression of MEX3A. RNA interference (RNAi) method was used to silence MEX3A in A549 and NCI-H292 cells. Cell counting kit-8 (CCK8) and Transwell assays were used to determine the effects of MEX3A knockout on proliferation, invasion, and migration in NSCLC cells. Flow cytometry was used to analyze the effects of MEX3A knockout on cell cycle and apoptosis. Results: A549 and NCI-H292 cells showed high expression of MEX3A. After silencing MEX3A, the proliferation, invasion, and migration of NSCLC cells were significantly decreased, while the cell cycle was blocked at G2/M phase and its apoptotic ability was weakened. Conclusions: MEX3A may play an important role as an oncogene in the growth and proliferation of NSCLC cells.

Evaluation of the Combination of Azithromycin and Naphthoquine in Animal Malaria Models.

Combination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only a few other combinations are now available. Increasing concern regarding the emergence and spread of artemisinin resistance in Plasmodium falciparum has led to a need for the development of new antimalarials. Moreover, the efficacy of current available chemoprophylaxis is compromised by drug resistance and noncompliance due to intolerable adverse effects or complicated dosing regimens. Therefore, new antimalarials that are more effective, safer, and more convenient are also urgently needed for malaria chemoprophylaxis. In this study, we assessed the combination of azithromycin and naphthoquine in animal malaria models. A dose-dependent interaction was observed in Peters' 4-day suppressive test on P. berghei K173-infected mice. Moreover, at inhibition levels of ≥90%, synergistic effects were found for combinations at various ratios. At an optimal dose ratio of 1:1, the combination of azithromycin and naphthoquine acted synergistically even by 4 weeks after the first dose and provided a more effective and sustained prophylaxis than did naphthoquine alone in blood-stage P. berghei K173 and P. cynomolgibastianelli L challenge models. The ability of the combination to delay and slow down resistance development in P. berghei K173 was also shown. These results showed clear evidence for the benefit of the combination therapy with azithromycin and naphthoquine in animal malaria models, providing some insight for further development of this therapy for malaria treatment and prophylaxis.

Analysis on the influencing factors of 31-day unplanned readmission in obstetrics department of public hospitals / 中华医院管理杂志

Objective:To explore the influencing factors of 31-day unplanned readmission in obstetrics.Methods:The medical records and relevant clinical data of 29 public hospitals in a province in 2017 were collected to construct a two-level logistic regression model on the influencing factors of 31-day unplanned readmission.Results:In 2017, there were 71 330 obstetric patients discharged from 29 public hospitals, 690 of whom were unplanned readmitted in 31 days, accounting for 0.97%. The type of medical insurance payment, number of previous hospitalization, condition of previous hospitalization, age, history of cesarean section, pregnancy complications and complications during delivery were all the factors influencing the 31-day unplanned readmission of obstetrics.Conclusions:The condition of 31-day unplanned readmission could be influenced by the factors of sociology, previous visit and clinical. These factors should be considered reasonably in the evaluation and management of obstetric quality.

Effect of Physical Activity on Hospital Service Use and Expenditures of Patients with Coronary Heart Disease: Results from Dongfeng-Tongji Cohort Study in China.

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.

Effect of Lumbricus Peptides on TLR4/NF-<i>κ</i>B Signaling Pathway in Spontaneous Hypertensive Rat Kidney / 中国实验方剂学杂志

@# <b>Objective:</b>to observe the effect and mechanism of lumbricus peptides on early renal injury in spontaneous hypertensive rats (SHR) based on Toll-like receptors 4 (TLR4)/nuclear factor-<i>κ</i>B(NF-<i>κ</i>B) signaling pathway. <b>Method:</b>The 40 SHRs were randomly divided into model group (equal volume of distilled water by intragastric administration), lumbricus peptides low, middle and high dose groups (126, 252, 504 mg·kg^-1), and Benazepril group (0.9 mg·kg^-1), <i>n</i>=8 in each group. 8 male rats with normal blood pressure at the same age were set as the normal control group,with equal volume of distilled water. After treatment for 60 consecutive days, enzyme-linked immunosorbent assay (ELISA) was used to determine microalbumin (mAlb)and <i>N</i>-acetyl-<i>β</i>-<i>D</i>-glucosaminidase (NAG) content in 24 h urine as well as the level of serum angiotensinⅡ (AngⅡ). Ultrastructural changes of rat kidneys were observed by transmission electron microscope. Western blot was used to detect renal TLR4, NF-<i>κ</i>B p65 protein levels. Immunohistochemical method was used to detect renal tumor necrosis factor-<i>α</i> (TNF-<i>α</i>) and interleukin 10 (IL-10) expression. <b>Result:</b>As compared with the normal control group, the levels of urine mAlb, NAG and serum Ang Ⅱ were increased in the model group (<i>P</i><0.05); the expression of TLR4 and NF-<i>κ</i>B p65 protein was increased (<i>P</i><0.05); expression of TNF-<i>α</i> was increased (<i>P</i><0.05), while IL-10 expression was decreased (<i>P</i><0.05). Transmission electron microscopy of kidney tissues showed that most of the glomeruli of the model group had podocyte foot process fusion, mesangial cells and mesangial matrix hyperplasia. As compared with the model group, the levels of urine mAlb, NAG, and serum Ang Ⅱ were decreased in the rats in lumbricus peptides groups and benazepril group (<i>P</i><0.05); the expression of TLR4 and NF-<i>κ</i>B p65 protein was decreased (<i>P</i><0.05); the positive expression of TNF-<i>α</i> in kidney was decreased to different extent (<i>P</i><0.05), but the expression of IL-10 was increased (<i>P</i><0.05). Transmission electron microscopy of kidney tissues showed that the damage of kidneys in rats after administration of high-dose lumbricus peptides and benazepril was improved in varying degrees. <b>Conclusion:</b>lumbricus peptides can reduce early renal damage in SHRs, and its mechanism may be achieved by regulating the AngⅡ-TLR4/NF-<i>κ</i>B pathway.

Effects of alcohol on benign prostate hyperplasia induced by testosterone propionate in mice / 中国应用生理学杂志

OBJECTIVE@#To study the effects of alcohol administration on benign prostate hyperplasia(BPH) and the reproductive toxicity during development of benign prostate hyperplasia.@*METHODS@#Seventy adult male Kunming mice were randomly divided into seven groups:control (group CON), negative control (group NC, injected subcutaneously with soybean oil, 25 mg/(kg·d), intragastric administration of distilled water, 7.5 ml/(kg·d)), alcohol for 7 and 21 days (group AL7 and AL21, intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)), testosterone propionate for 7 and 21 days (group TP7 and TP21, injected subcutaneously with testosterone propionate, 25 mg/(kg·d)), testosterone propionate+alcohol for 7 days (group TP+AL7, injected subcutaneously with testosterone propionate, 25 mg/(kg·d), and intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)),10 mice in each groups. Twenty-four hours after the last administration, mice were sacrificed. The indexes of prostate and testis and the parameters of sperm were determined in mice. The levels of free radicals, antioxidation and histopathological changes in testis and prostate were determined.@*RESULTS@#Compared with the control, TP7d group, AL7 and AL21d groups, the prostate coefficient of TP + AL7d group was increased significantly and the quantity and quality of sperm were decreased significantly (0.05).@*CONCLUSIONS@#The typical BPH state could be induced after 7-day treatment of testosterone propionate and alcohol. The testicular and sperm were damaged which enhanced the oxidative stress in reproductive system. The results indicated that alcohol could significantly promote the prostate hyperplasia induced by testosterone propionate in mice.

Impact of organizational and individual factors on patient-provider relationships: A national survey of doctors, nurses and patients in China.

OBJECTIVES: To provide an empirical examination of patient-provider relationships (PPR) and its association with organizational and individual factors. METHODS: A national cross-sectional survey was conducted by stratified cluster sampling in 77 hospitals across seven provinces in China between July 2014 and April 2015, involving 3621 doctors, 5561 nurses, and 8022 patients with response rates of 62.93%, 61.16%, and 33.08%, respectively. Self-perceived PPR was the outcome variable. Organizational factors included hospital type (western medicine [WM] and traditional Chinese medicine [TCM] hospital); hospital level (tertiary and secondary hospital); area of specialization (internal medicine and surgery); ratio of doctors (nurses) to ward beds; doctors/nurses' concerns about performance assessment; and patients' perceptions of healthcare cost. Individual factors included consultation, listening to patients and socio-demographic factors. RESULTS: 54.6% of doctors, 36.6% of nurses, and 10.2% of patients perceived PPR as poor. Organizational factors independently associated with providers' perception of poor PPR included hospital type (WM vs TCM: OR = 1.25 [95% CI: 1.06-1.47]) and concerns about performance assessment (high vs low levels: OR = 1.40 [95% CI: 1.14-1.72]) for doctors, and concerns about performance assessment (average vs low levels: OR = 0.79 [95% CI: 0.67-0.93]) for nurses. Those associated with patients' perception of poor PPR included hospital type (WM vs TCM: OR = 0.63 [95% CI: 0.53-0.74]) and hospital level (tertiary vs secondary: OR = 0.65 [95% CI: 0.51-0.82]). Doctors and nurses reporting listening to patients "frequently" had better perceptions of PPR (OR = 0.46 [95%CI: 0.38-0.56] and 0.49 [95% CI: 0.41-0.59] for doctors and nurses, respectively), as did their patients (OR = 0.24 [95% CI: 0.18-0.31] and 0.54 [95% CI: 0.35-0.84] for doctors and nurses, respectively). CONCLUSIONS: Although our findings require validation in different organizational settings given the likely variability of these associations across systems, our results suggest that implementing moderate levels promoting the level of medical treatment, and broadening doctors/nurses training regarding listening to patients, may benefit to enhance PPR.

Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone: Clinical, Virological, Immunological, and Evolutionary Analyses.

We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors. The viruses converged in a new clade within sublineage 3.2.4, which had a significantly lower case fatality rate.

Risk factors for congenital heart disease in Chinese neonates: a Meta analysis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the major risk factors for congenital heart disease (CHD) in Chinese neonates and to provide a reference for the prevention of CHD.</p><p><b>METHODS</b>A literature search was performed to collect the case-control studies on the risk factors for CHD in Chinese neonates published in 2001-2016. The relevant data were extracted accordingly. The quality of included studies was assessed by Newcastle-Ottawa Scale. Sensitivity analysis was conducted using different models to analyze the same data. The publication bias was assessed by Egger's test.</p><p><b>RESULTS</b>A total of 17 case-control studies involving 2 930 cases and 4 952 controls were included. The Meta analysis showed that the major risk factors for CHD in Chinese neonates were as follows: mother with advanced age (OR=2.649, 95%CI: 1.675-4.189), cold or fever (OR=4.558, 95%CI: 2.901-7.162), medication use in early pregnancy (OR=3.961, 95%CI: 2.816-5.573), passive smoking (OR=2.766, 95%CI: 1.982-3.859), abnormal childbearing history (OR=2.992, 95%CI: 1.529-5.856), noise exposure (OR=3.030, 95%CI: 1.476-6.217), radiation exposure (OR=2.363, 95%CI: 1.212-4.607), decoration (OR=4.979, 95%CI: 3.240-7.653), gestational diabetes (OR=5.090, 95%CI: 3.132-8.274), and pet raising (OR=2.048, 95%CI: 1.385-3.029).</p><p><b>CONCLUSIONS</b>Mothers with advanced age, cold or fever, medication use in early pregnancy, passive smoking, abnormal childbearing history, noise exposure, radiation exposure, decoration, gestational diabetes, and pet raising may increase the risk of CHD in Chinese neonates.</p>

Association between depression during pregnancy and low birth weight in neonates: a Meta analysis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the association between depression during pregnancy and low birth weight in neonates, and to provide a scientific basis for the prevention of low birth weight.</p><p><b>METHODS</b>Cohort studies on the association between depression during pregnancy and low birth weight were collected and a Meta analysis was performed. Data were extracted independently by two investigators, and quality assessment was performed according to Newcastle-Ottawa Scale. The Egger's test was used to evaluate publication bias.</p><p><b>RESULTS</b>A total of 12 cohort studies with 37 192 samples were included. The results of the Meta analysis showed that depression during pregnancy was associated with low birth weight (Z=2.08, P=0.038), and the neonates whose mothers had depression during pregnancy tended to have a high risk of low birth weight (RR=1.303, 95%CI: 1.015-1.672). The sensitivity analysis showed that the results of this Meta analysis were stable and reliable, and the Egger's test showed no publication bias.</p><p><b>CONCLUSIONS</b>Depression during pregnancy may be a risk factor for low birth weight in neonates.</p>

Transcatheter arterial chemoembolization in combination with percutaneous ablation therapy for the treatment of hepatocellular carcinoma: a meta-analysis / 介入放射学杂志

Objective To compare the differences in the long-term survival rate and the tumor shrinkage rate of inoperable hepatocellular carcinoma (HCC) between transcatheter arterial chemoembolization (TACE) combined with percutaneous ablation therapy and simple TACE therapy in order to provide the basis for the clinical treatment of HCC.Methods Randomized controlled trials (RCT) for comparing the difference in survival rates between TACE plus PA and simple TACE for inoperable HCC were searched from medical literature database,from which the relevant data were extracted.According to Cochrane manual standard,the quality of inclusion literature was evaluated.Results A total of 15 RCT papers were included in this study,including 859 HCC patients.The results of meta-analysis showed that all the 1-year,2-year and 3-year survival rates in TACE plus PA group were better than those in simple TACE group (RR=1.454,95％CI=1.333and 1.586,Z=8.56,P＜0.001;RR=1.781,95％CI=1.511 and 2.099,Z=6.88,P＜0.001;RR=2.351,95％CI=1.808 and 3.059,Z=6.37,P＜0.001,respectively).The tumor shrinkage rate in TACE plus PA group was also better than that in simple TACE group (RR=1.314,95％CI=1.190 and 1.452,Z=5.38,P＜0.001).The sensitivity analysis indicated that the results of the differences in survival rate and tumor shrinkage rate between the two groups were reliable.Conclusion The 1-year,2-year and 3-year survival rates as well as the tumor shrinkage rate of TACE plus PA group are higher than those of simple TACE group.

"Integration of traditional medical journals and new media in ""Internet + era""" / 中华医学图书情报杂志

Objective To study the integration of traditional medical journals and new media in the Internet +era. Methods The papers published in journals were integrated and a characteristic single disease misdiagnosis database was developed for providing precise and accurate information by making full use of the contributing, revie-wing, editing and proofreading platform into which the short message service, alipay or third party payment service and WeChat service were linked. Results The platform makes convenient for the authors, editors and reviewers of manuscripts, the database contributes to the deep development of journal contents and activates the journal vitality. Conclusion The traditional media can improve the work efficiency, integrate the journal contents and provide the characteristic service by making full use of modern technologies, thus contributing to the further development of journals.

Polymorphism of XRCC1 gene and its relation with genetic susceptibility of nasopharyngeal carcinoma in chinese living in jiangsu, zhejiang province and shanghai / 第二军医大学学报

Objective To study the polymorphism of XRCC1 gene and its relation with genetic susceptibility of the nasopharyngeal carcinoma (NPC) in Chinese living in Jiangsu, Zhejiang Province and Shanghai. Methods A case-control study was performed with 87 NPC patients and 94 healthy controls ofHan nationality in Chinese living in Jiangsu, Zhejiang Province and Shanghai. The two groups were matched by sex and age. PCR-RFLP technique was used to explore the relation of different XRCC1 polymorphismswith the susceptibility of NPC. Results The frequencies of the genotypes of XRCC1 Argl94Trp and Arg399Gln were similar between NPC andcontrol groups. The risk of NPC individuals with the Trp194Trp genotype was reduced compared with that in those with Argl94Arg genotype, but with no significant differences (0R = 0. 41, 95% CI:0. 081. 65, P = 0. 21). No association was observed between the genetic susceptibility ofNPC and other Argl94Trp variants or all Arg399Gln variants. Conclusion Our findings suggest that the polymorphism of XRCC1 has no association with the risk of nasopharyngeal carcinoma inChinese living in Jiangsu, Zhejiang Province and Shanghai, but the Trp194Trp variant genotype may be associated with a reduced risk of NPC.