Safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant chemotherapy combined with immunotherapy / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.

Expression of MSI1 and HER2 in mammary Paget's disease and their correlation with clinicopathological features and prognosis / 中华病理学杂志

Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.

Clinicopathological and molecular features of metaplastic thymoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.

Quantifying the duration of the preclinical detectable phase in cancer screening: a systematic review / 한국역학회지

OBJECTIVES@#The aim of this study was to provide an overview of published mathematical estimation approaches to quantify the duration of the preclinical detectable phase (PCDP) using data from cancer screening programs. @*METHODS@#A systematic search of PubMed and Embase was conducted for original studies presenting mathematical approaches using screening data. The studies were categorized by mathematical approach, data source, and assumptions made. Furthermore, estimates of the duration of the PCDP of breast and colorectal cancer were reported per study population. @*RESULTS@#From 689 publications, 34 estimation methods were included. Five distinct types of mathematical estimation approaches were identified: prevalence-to-incidence ratio (n=8), maximum likelihood estimation (n=16), expectation-maximization algorithm (n=1), regression of observed on expected (n=6) and Bayesian Markov-chain Monte Carlo estimation (n=5). Fourteen studies used data from both screened and unscreened populations, whereas 19 studies included only information from a screened population. Estimates of the duration of the PCDP varied between 2 years and 7 years for breast cancer in the Health Insurance Plan study (annual mammography and clinical breast examinations in women aged 40-64 years) and 2 years and 5 years for colorectal cancer in the Calvados study (a guaiac fecal occult blood test in men and women aged 45-74 years). @*CONCLUSIONS@#Different types of mathematical approaches lead to different estimates of the PCDP duration. We advise researchers to use the method that matches the data available, and to use multiple methods for estimation when possible, since no method is perfect.

Study on the association between occupational noise exposure and cardiovascular diseases / 中华劳动卫生职业病杂志

Occupational noise is one of the most common occupational hazards in the workplace. Long-term exposure to occupational noise could not only lead to the damage of the hearing system, but also may cause a certain impact on the cardiovascular system. Studies have shown that occupational noise exposure was positively associated with cardiovascular diseases, including hypertension, coronary heart disease and myocardial infarction. However, the results of studies on occupational noise exposure and stroke are still controversial. This paper reviews the relationship between occupational noise exposure and hypertension, coronary heart disease, stroke, myocardial infarction by summarizing the epidemiological data of domestic and foreign population in recent years. Our study could provide evidence for the design and implementation of well-designed epidemiological and mechanism studies, and the recognition of the role of occupational noise exposure in the occurrence and development of cardiovascular diseases, so as to better protect workers' health.

Application of generalized estimation equations to establish prediction equation for tuberculosis drug resistance in Zhejiang province / 中华流行病学杂志

Objective: Drug-resistant tuberculosis (TB) may be resistant to one or multiple anti-TB drugs. We used generalized estimation equations to analysis the risk factors of drug-resistant TB and provide information for the establishment of a warning model for these non-independent data. Methods: The drug susceptibility test and questionnaire survey were performed in sputum positive TB patients from 30 anti TB drug-resistance surveillance sites in Zhejiang province. The generalized estimation model was established by the GENMOD module of SAS, with resistance to 13 kinds of anti-TB drugs as dependent variables and possible influencing factors, such as age, having insurance, HBV infection status, and history of anti-TB drug intake, as independent variables. Results: In this study, the probability of drug resistance at baseline level was 20.26%. Age, insurance, whether being co-infected with HBV, and treatment history or treatment withdrawal were statistically significantly correlated with anti-TB drug resistance. The prediction equation was established according to the influence degree of the factors mentioned above on drug resistance. Conclusion: The generalized estimation equations can effectively and robustly analyze the correlated binary outcomes, and thus provide more comprehensive information for drug resistance risk factor evaluation and warning model establishment.

Dynamic variations of BMI and influencing factors among HIV/AIDS patients receiving highly active antiretroviral therapy in Liuzhou, Guangxi Zhuang Autonomous Region, 2013-2014 / 中华流行病学杂志

Objective: To understand the dynamic variation of BMI and influencing factors among HIV/AIDS patients receiving highly active anti-retroviral therapy (HAART) in Liuzhou, Guangxi Zhuang Autonomous Region (Guangxi). Methods: HIV/AIDS patients receiving HAART for the first time since 1 January 2013 were selected. Data on BMI was analyzed among patients receiving HAART at baseline,6 months and 12 months after treatment. By using the general linear model repeated measures of analysis of variance, BMI dynamic variations and influencing factors were described and analyzed. Results: The average BMI of 2 871 patients at baseline, 6th months and 12th months appeared as (20.65±3.32), (20.87±3.22) and (21.18±3.20), respectively, with differences all statistically significant (F=18.86, P<0.001). BMI were increasing over time with treatments (F=37.25, P<0.001). Main influencing factors were noticed as: age, sex, marital status, baseline data of CD(4)(+)T cells and the WHO classification on clinical stages. Conclusions: Higher proportion of BMI malnutrition counts was seen among patients before receiving HAART in Liuzhou. BMI of the patients that were on HAART seemed being influenced by many factors. It is necessary to select appropriate treatment protocols on different patients so as to improve the nutritional status of the patients.

Association between total cholesterol and risk of lung cancer incidence in men: a prospective cohort study / 中华流行病学杂志

Objective: To assess the association and intensity of baseline TC level with the incidence of lung cancer in men in China. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history, anthropometry and TC level were collected at the baseline interview, as well as the information of newly-diagnosed lung cancer cases during the follow-up period. According to guidelines for blood lipids in Chinese adults and the distribution in the population, TC level was classified into five groups as followed: <160, 160-, 180-, 200- and ≥240 mg/dl, with the second quintile group (160- mg/dl) serving as the referent category. Cox proportional hazards regression model and restricted cubic spline (RCS) model were used to evaluate the association and the nonlinear association between baseline TC level and the risk of lung cancer in the men. Results: By December 31, 2014, for the 109 884 men, a follow up of 763 819.25 person-years was made with a median follow-up period of 7.88 years. During the follow up, 808 lung cancer cases were identified. After adjustment for age, education level, income level, smoking status, alcohol consumption level, history of dust exposure, FPG level and BMI, HR (95%CI) of lung cancer for men with lower TC level (<160 mg/dl) and higher TC level (≥240 mg/dl) were 1.34 (1.04- 1.72) and 1.45 (1.09-1.92), respectively, compared with men with normal TC level (160- mg/dl). The results didn't change significantly after exclusion of newly diagnosed cancer cases within 2 years of follow up and subjects with the history of hyperlipidemia. Conclusion: Our results showed that TC might be associated with higher risk of lung cancer. Men with lower TC level or higher TC level had higher risk for lung cancer. Keep moderate TC level might be one of the effective precaution for the prevention of lung cancer.

New psychoactive substances abuse among patients with access to methadone maintenance treatment in Jiangsu province: a case-control study / 中华流行病学杂志

Objective: To explore the reasons and factors associated with new psychoactive substances abuse among patients with access to methadone maintenance treatment (MMT). Methods: A well-developed questionnaire and urine tests were used to collect information about demographic characteristics, condition of MMT and drug abuse, family and social support of MMT clients. A 1∶1 matched case-control study was conducted, and conditional logistic regression model was used to identify factors associated with new psychoactive substances abuse. Results: A total of 212 (106 pairs) clients receiving MMT were recruited, and most of them were males (78.3%, 166/212), married or cohabitant (48.6%, 103/212) and unemployed (63.2%, 134/212). The average age of the clients was (45.1±7.2) years. The main types of abused new psychoactive substances were benzodiazepine (62.3%, 66/106) and methamphetamine (39.6%, 42/106). The proportion of abusing multi new psychoactive substances was 8.5% (9/106). Results from multivariate conditional logistic regression analysis indicated that using opioid drug during the past 6 months of MMT treatment might increase the risk of abusing new psychoactive substances (OR=3.25, 95%CI: 1.35-7.79), benzodiazepine (OR=3.25, 95%CI: 1.11- 9.47) and methamphetamine (OR=13.31, 95%CI: 1.12-158.01). Moreover, MMT for more than9 years reduced the risk of abuse of new psychoactive substances (OR=0.03, 95%CI: 0.01-0.21), benzodiazepine (OR=0.02, 95%CI: 0.00-0.36) and methamphetamine (OR=0.02, 95%CI: 0.00-0.69). Conclusion: Less new psychoactive substances abuse might be associated with longer duration of MMT treatment. And inappropriate support from family and friends might increase the risk of abusing new psychoactive substances in MMT clients, especially in clients who used opioid.

Study on relationship between prevalence or co-prevalence of risk factors for cardiovascular disease and blood pressure level in adults in China / 中华流行病学杂志

Objective: To study the relationship between blood pressure level and major risk factors for cardiovascular diseases in adults in China. Methods: A total of 179 347 adults aged ≥18 years were recruited from 298 surveillance points in 31 provinces in China in 2013 through complex multistage stratified sampling. The survey included face to face interview and physical examination to collect information about risk factors, such as smoking, drinking, diet pattern, physical activity, overweight or obesity, and the prevalence of hypertension. The blood pressure was classified into 6 levels (ideal blood pressure, normal blood pressure, normal high blood pressure and hypertension phase Ⅰ, Ⅱ and Ⅲ). The relationship between the prevalence or co-prevalence of risk factors for cardiovascular disease and blood pressure was analyzed. Results: The adults with ideal blood pressure, normal blood pressure, normal high pressure, hypertension phase Ⅰ, Ⅱ and Ⅲ accounted for 36.14%, 22.77%, 16.22%, 16.43%, 5.97% and 2.48%, respectively. Among them, the blood pressure was higher in men, people in Han ethnic group and those married, and the blood pressure was higher in those with older age, lower income level and lower education level, the differences were all significant (P<0.05). Whether taking antihypertensive drug or not, co-prevalence of risk factors influenced the blood pressure levels of both sexes (P<0.05), and the blood pressure levels of those taking no antihypertensive drug was influenced more by the co-prevalence of risk factors. Finally, multiple logistic analysis showed that the risks for high blood pressure in adults with 1, 2 and ≥3 risk factors were 1.36, 1.79 and 2.38 times higher, respectively, than that of the adults without risk factor. Conclusion: The more the risk factors for cardiovascular disease in adults, the higher their blood pressure were. It is necessary to conduct comprehensive behavior intervention targeting ≥ 2 risk factors for the better control of blood pressure in general population.

Alcohol consumption and the risk of lung cancer in males: a prospective cohort study / 中华流行病学杂志

Objective: To investigate the association between alcohol consumption and lung cancer risk in Chinese males. Methods: Information on alcohol consumption and outcomes were collected on a biennial basis among males in Kailuan Cohort (2006-2015). In addition, electronic databases of hospitals affiliated to Kailuan Community, Insurance Systems of Kailuan Community and Tangshan were also used for supplementary information retrieval. Cox proportional hazards regression models were used to evaluate the hazard ratio (HR) and 95%CI of baseline frequency and type of alcohol consumption associated with lung cancer risk in males. Non-drinkers were used as control group. Results: A total of 101 751 males were included and 913 new lung cancer cases were identified in the Kailuan male cohort study, with a total follow-up time of 808 146.56 person-years and a median follow-up time of 8.88 years by 31 December 2015. After adjusting for potential confounding factors, the HR of former drinkers, occasional drinkers (<1/day) and drinkers (≥1/day) were 1.30 (95%CI: 0.90-1.88), 0.80 (95%CI: 0.64-1.01) and 1.04 (95%CI: 0.85-1.27), respectively, compared with non-drinkers. In addition, drinking beer/red wine (HR=0.91, 95%CI: 0.69-1.20) and white wine (HR=0.99, 95%CI: 0.83-1.19) showed no significant association with lung cancer. The results were similar when stratified analysis were conducted. Conclusion: Our study results don't support the hypothesis that alcohol consumption is significantly associated with the risk of lung cancer in males.

Spatial-temporal distribution characteristics of hepatitis E in Shanghai, 2006-2016 / 中华流行病学杂志

Objective: To understand the epidemiologic characteristics and spatial-temporal distribution of hepatitis E in Shanghai between 2006 and 2016. Methods: The reported incidence of hepatitis E and health facilities' information between 2006 and 2016 were collected from the China Information System for Disease Control and Prevention. The geographic information were from Shanghai Surveying and Mapping Institute. The map scale was 1∶750 000. Global and local autocorrelation, and spatial-temporal detection methods were applied to determine the spatial-temporal characteristics of hepatitis E. Software ArcGIS 10.1 was used to analyze global and local spatial auto correlation of hepatitis E spatial clusters. Software SaTScan 9.4.4 was used to conduct scan for exploring the areas of hepatitis E temporal spatial clusters. Results: A total of 6 048 cases of hepatitis E were reported in Shanghai during 2006-2016. The average incidence was 2.14/100 000. Spatial auto correlation analysis indicated that there was significant spatial positive correlations and spatial-temporal clustering of hepatitis E in Shanghai, and the "high-high cluster" was mainly located in the downtown of the city. Conclusion: Understanding the spatial-temporal clustering areas of hepatitis E cases in Shanghai from 2006 to 2016 is important to the reasonable allocation of public health resources and effective prevention and control of hepatitis E.

Application of computed tomography and magnetic resonance imaging fusion images for delineating gross tumor volume in three-dimensional conformal radiotherapy of nasopharyngeal carcinoma

Background: To evaluate computed tomography [CT] and magnetic resonance imaging [MRI] fusion images for delineating gross tumor volume [GTV] in three-dimensional conformal radiotherapy [3D-CRT] of nasophanrygeal carcinoma [NPC], and compare treatment outcomes between CT- and CT+MRI-based targets

Materials and Methods: A total of 120 NPC patients treated with 3D-CRT were included, in which, 60 each were treated with CT-based and 60 with CT+MRI fusion targets. We explored the clinical application of CT+MRI fusion targets and compared the 1-, 3-, and 5-year survival and relapse rates between both targets

Results: The clinical characteristics and treatment factors were well balanced. The differences in public volume using CT alone in the CT+MRI [Group A] and the CT arm [Group B] were not significant [33.6+/-2.18 vs. 34.3+/-2.98, P > 0.05]. The public volumes of GTV in the two arms were 49.48+/-2.46 cm[3] and 33.6+/-2.18 cm[3] respectively [P < 0.05]. CT+MR fusion images did not influence the one-, three-, and 5-year survival rates [100% vs. 98.3%, 85.0% vs. 81.2%, and 73.3% vs. 68.3%, respectively]. The three- and 5-year out-of-field progression was reduced in the CT+MRI arm. However, only the difference in 3-year out-of-field relapse rate was significant [3.3% vs. 13.3%; P < 0.05]. The incidence of acute toxicities was similar between groups

Conclusion: The variability in GTV delineation in NPC was ascribed to intermodality and not interobserver variability. CT+MR fusion images likely reduced the 3-year out-of-field relapse rate

Predictive values of TNF-alpha, IL-6, IL-10 for radiation Pneumonitis

Background: To investigate the expression of TNF-alpha, IL-6, IL-10 in the plasma of patients with lung cancer who received radiation therapy [RT], and to analyze the correlation between these cytokines and radiation pneumonitis [RP]. Materials and Methods: Patients with lung cancer who received 3D-CRT in our hospital were prospectively evaluated. Circulating cytokine levels were measured with ELISA before RT and at the end of RT. Regular follow-up was undertaken 3 months after RT. Statistical analysis was applied to determine the relevance of cytokines to radiation-induced lung injury. Results: Of 104 patients, 29 [27.9%] developed RP. The levels of TNF-alpha and IL-6 levels in the plasma after RT were significantly higher than before RT [p<0.05], whereas IL -10 levels were significantly lower after RT than before RT [p<0.05]. Before RT, TNF-alpha levels were higher in RP group [p<0.05],but there were no differences in TNF-alpha levels after RT. No association was observed between IL-6 and IL-10 levels and the risk of RP. Univariate analysis showed that baseline pulmonary function, smoking history, histopathology, lung volume receiving >/=20 Gy [V20], Mean lung dose [MLD] and total radiation dose were related to RP, but only MLD was an independent risk factor for RP in lung cancer patients [OR>1]. Conclusion: TNF-alpha levels in plasma were closely related to RP but still cannot be used as predictors for RP

Efficacy of pyrimethamine/sulfadoxine versus chloroquine for the treatment of uncomplicated falciparum malaria in children aged under 5 years

The children aged under 5 years from vast African areas badly suffer from falciparum malaria and many of them die of this disease. Therapeutic efficacy of anti-malaria drugs, especially pyrimethamine-sulfadoxine [PS] and chloroquine [CQ] to falciparum malaria is frequently evaluated and reported in recent 10 years. Unfortunately, to date, these widespread materials and researches have not been systematically collected and analyzed. In our study, two investigators were employed to widely and independently gather researches on efficacy of PS vs. CQ mono-therapy of falciparum malaria in children aged below 5 years in unpublished and published databases. Meta-analyses were conducted in categories of PS group and CQ group respectively. Pooled OR of PS vs. CQ was 0.11 [95%CI, 0.05-0.24]. PS showed higher therapeutic efficacy to falciparum malaria in less-than-5-year children than CQ. Random model was chosen to analyze for the heterogeneity existence between different studies. Subgroup analyses were performed, but heterogeneity was still presented. Heterogeneity might be caused by different resistance of falciparum malaria to PS and CQ in different settings. Malaria type associated with parasite species, basic information of PS and CQ, and PS and CQ resistant malaria control measures were demonstrated and discussed respectively in detail in this article

Current approaches to assess QTc prolongation for small molecule drug development / 中国药理学与毒理学杂志

Assessment of QTc prolongation is a critical step for small molecule drug development.ICH S7B continues to be the main frame to guide the assessment for this potential cardiovascular risk.The ICH guideline outlines a 3-step approach to QTc prolongation,including in vitro bERG inhibition,ex vivo action potential duration (APD),and in vivo animal telemetry approch.Dog,monkey,swine,rabbit,ferret,and guinea pig are the common laboratory animals used for in vivo electrophysiology studies,especially using conscious Beagle Dog. In addition to all these guideline standard studies,many newly developed approaches,such as receptor binding for hERG inhibition,ex vivo methods such as perfused rabbit heart or guinea pig heartare are useful models for this purpose.All these methods display good correlation to clinic outcomes,and are low cost and have rapid turn-around time in nature; so that,they can help rapidly and predict this potential cardiac liability,resulting into accelerating process for small molecule drug candidate development.

Biodegradation of cypermethrin by a newly isolated actinomycetes HU-S-01 from wastewater sludge

A new cypermethrin degrading strain was isolated from wastewater sludge using enrichment technique. On the basis of morphological, physiological, biochemical characteristics tests and 16S rDNA sequence analysis, the strain was determined to be a Streptomyces species, probably a strain of Streptomyces parvulus, so it was designated as Streptomyces sp. HU-S-01. The strain Streptomyces sp.HU-S-01 is aerobic and optimum growth temperature for the strain was found to be 26-28°C with initial pH range 6.0-9.0 and pH 7.5 was found to be the optimum. This strain can also completely degrade 3-phenoxybenzoic acid within 96 h at the concentration of 50 mg/L. The kinetic constants Vmax, Km, Kcat and Kcat/ Km of enzyme for cypermethrin were 1.236 micro mol/min, 6.418 micro mol/mL, 13.493 min and 2.102 mL/mol.min, respectively. The degradation products of cypermethrin were identified using gas chromatograph-mass spectrometric [GC-MS] analysis. The degradation pathway followed by HU-S-01 involves oxidative as well as hydrolyzing. Biodegradation ability of strain Streptomyces sp. HU-S-01 without toxic byproducts reveals its potential for further study as a biological agent for the remediation of soil, water or crops, contaminated with cypermethrin

Hybrid anaerobic baffled reactor for treatment of desizing wastewater

Polyvinyl alcohol-containing desizing wastewater discharged within final textile wastewater has a great impact to the environment due to its poor biodegradability. An improved lab-scale hybrid anaerobic baffled reactor was developed to treat desizing wastewater. The modification was achieved by increasing the height of hybrid anaerobic baffled reactor and application of proper effluent recycle enabled to increase the ability of entrapping microbe-rich small particles in the reactor and prompted the formation of granules. The significant difficulty in hybrid anaerobic baffled reactor operation is the slow start-up procedure, which is crucial to the overall polyvinyl alcohol-containing desizing wastewater treatment. Therefore, the ability of a hybrid anaerobic baffled reactor, treating desizing wastewater, to achieve a prompt start-up was studied at lab-scale. Results showed that inoculated with anaerobic granular sludge and adoption of effluent recycle during start-up, the system demonstrated a good performance of polyvinyl alcohol removal efficiency [above 17.2%] and satisfactory stability of pH and alkalinity in effluent [range around 7.4-8.0 and 700-920 mg/L, respectively] and the sludge appeared obviously granulation. Thus, the prompt start-up was achieved after 60 days. The start-up strategy used for this process has achieved its goals by creating an active microbial population. The improved lab-scale hybrid anaerobic baffled reactor proved to be an efficient reactor configuration for the treatment of desizing wastewater, which favored the prompt start-up of hybrid anaerobic baffled reactor. The results also provide evidence to modify the design of anaerobic baffled reactor to improve reactor performance