The impact of the world's first regulatory, multi-setting intervention on sedentary behaviour among children and adolescents (ENERGISE): a natural experiment evaluation.

BACKGROUND: Regulatory actions are increasingly used to tackle issues such as excessive alcohol or sugar intake, but such actions to reduce sedentary behaviour remain scarce. World Health Organization (WHO) guidelines on sedentary behaviour call for system-wide policies. The Chinese government introduced the world's first nation-wide multi-setting regulation on multiple types of sedentary behaviour in children and adolescents in July 2021. This regulation restricts when (and for how long) online gaming businesses can provide access to pupils; the amount of homework teachers can assign to pupils according to their year groups; and when tutoring businesses can provide lessons to pupils. We evaluated the effect of this regulation on sedentary behaviour safeguarding pupils. METHODS: With a natural experiment evaluation design, we used representative surveillance data from 9- to 18-year-old pupils before and after the introduction of the regulation, for longitudinal (n = 7,054, matched individuals, primary analysis) and repeated cross-sectional (n = 99,947, exploratory analysis) analyses. We analysed pre-post differences for self-reported sedentary behaviour outcomes (total sedentary behaviour time, screen viewing time, electronic device use time, homework time, and out-of-campus learning time) using multilevel models, and explored differences by sex, education stage, residency, and baseline weight status. RESULTS: Longitudinal analyses indicated that pupils had reduced their mean total daily sedentary behaviour time by 13.8% (95% confidence interval [CI]: -15.9 to -11.7%, approximately 46 min) and were 1.20 times as likely to meet international daily screen time recommendations (95% CI: 1.01 to 1.32) one month after the introduction of the regulation compared to the reference group (before its introduction). They were on average 2.79 times as likely to meet the regulatory requirement on homework time (95% CI: 2.47 to 3.14) than the reference group and reduced their daily total screen-viewing time by 6.4% (95% CI: -9.6 to -3.3%, approximately 10 min). The positive effects were more pronounced among high-risk groups (secondary school and urban pupils who generally spend more time in sedentary behaviour) than in low-risk groups (primary school and rural pupils who generally spend less time in sedentary behaviour). The exploratory analyses showed comparable findings. CONCLUSIONS: This regulatory intervention has been effective in reducing total and specific types of sedentary behaviour among Chinese children and adolescents, with the potential to reduce health inequalities. International researchers and policy makers may explore the feasibility and acceptability of implementing regulatory interventions on sedentary behaviour elsewhere.

Application of aptamer-conjugated graphene oxide for specific enrichment of microcystin-LR in Achatina fulica prior to matrix-assisted laser desorption ionization mass spectrometry.

Microcystin-LR (MC-LR), as a hepatotoxin, can cause liver swelling, hepatitis, and even liver cancer. In this study, MC-LR aptamer (Apt-3) modified graphene oxide (GO) was designed to enrich MC-LR in white jade snail (Achatina fulica) and pond water, followed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) analysis. Results indicated that the Apt-3/PEG/GO nanocomposites were highly specific to MC-LR, and the detection limit of MALDI-MS was 0.50 ng/mL. Moreover, the MC-LR can be released from nanocomposites at 75°C, thus, the reuse of Apt-3/PEG/GO is realized. Real sample analysis indicated that the Apt-3/PEG/GO nanocomposites coupled with MALDI-MS were efficient in detecting trace amounts of MC-LR in real samples. With the merits of being low cost, reusable, and easy to besynthesized, this Apt-3/PEG/GO MALDI-MS is expected to be comprehensively applied by anchoring suitable aptamers for different targets.

Neuroprotective effect of plasmalogens on AlCl3-induced Alzheimer's disease zebrafish via acting on the regulatory network of ferroptosis, apoptosis and synaptic neurotransmission release with oxidative stress as the center.

Plasmalogens (Pls) are considered to play a potential role in the treatment of neurodegenerative diseases. In the present study, an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 was established to investigate whether the marine-derived Pls could alleviate cognitive impairments of AD zebrafish. Behavioral tests were carried out to assess the athletic ability. The transcriptional profiles of zebrafish in the control, AD model and AD_PLS group were compared and analyzed to determine the potential mechanisms of dietary Pls on AD. The study found that Pls could reverse athletic impairment in the AD zebrafish model, and the expression levels of genes related to ferroptosis, synaptic dysfunction and apoptosis were significantly altered between experimental groups. Further analysis showed that all of these genes were associated with oxidative stress (OS). These data suggest that healthy protective role of marine-derived Pls on AD zebrafish may result from inhibition of ferroptosis and neuronal apoptosis, restoring synaptic neurotransmission release, and reducing neuroinflammation. Among them, Oxidative stress is acted as the center to connect different regulation pathways. This study provides evidence to support the essential roles of OS in pathogenesis of AD, and the application of Pls in relieving AD.

High prevalence of hyperuricemia and the association with metabolic syndrome in the rural areas of Southwestern China: A structural equation modeling based on the Zhuang minority cohort.

BACKGROUND AND AIMS: The prevalence of hyperuricemia (HUA) and metabolic syndrome (MetS) in the Zhuang minority had not been examined. We aimed to determine the prevalence of HUA and MetS, and explore the interrelationship among the serum uric acid to creatinine (SUA/Cr) ratio, MetS, and its components. METHODS AND RESULTS: A cross-sectional study was conducted with structured questionnaire and physical examination based on the Zhuang minority cohort. A Structural Equation Model was performed to examine the hypothesis link between the SUA/Cr ratio, MetS, and its components. 10,902 aged 35-74 years Zhuang minority adults were included. The total prevalence of HUA and MetS was 17.5% and 23.7%, respectively. The SUA/Cr ratio had a positive effect on MetS (the standardized coefficient ßr was 0.311 in males and 0.401 in females). The SUA/Cr ratio was positively associated with obesity (ßr = 0.215), dyslipidemia (ßr = 0.177), and high blood pressure (ßr = 0.034) in males and was positively associated with obesity (ßr = 0.303), dyslipidemia (ßr = 0.162), and hyperglycemia (ßr = 0.036) in females. CONCLUSIONS: The prevalence of HUA in the aged 35-74 years Zhuang minority adults was high while the prevalence of MetS was relatively low. As HUA is an earlier-onset metabolic disorder and the SUA/Cr ratio had a positive effect on MetS and its components, the prevention measures of MetS should be strengthened. And the SUA/Cr ratio can be used as an early warning sign to implement the intervention measures of MetS.

The lead time and geographical variations of Baidu Search Index in the early warning of COVID-19.

Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of "COVID-19 epidemic", "Novel Coronavirus" and "COVID-19" can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0-28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5-8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1-3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (rs:0.70-0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase.

High Prevalence of Hyperuricemia and Associated Factors among Zhuang Adults: A Cross-Sectional Study Based on the Ethnic Minority Population Cohort in the Southwestern China.

The highest prevalence of hyperuricemia was found in Zhuang minority adults in two national surveys in China, with only 1% Zhuang study subjects. However, the prevalence of hyperuricemia and the associated factors in Zhuang adults have not been well-addressed. A cross-sectional study was conducted to explore the prevalence of hyperuricemia and the common comorbidities, and the associated factors in Zhuang adults based on the Guangxi Ethnic Minority Population Cohort. Among 11,175 Zhuang adults aged 35-74 years, the age- and sex-standardized prevalence rate was 18.1% for hyperuricemia and 1.1% for gout. The standardized prevalence rate and awareness rate were 31.6% and 32.3%, respectively, for hypertension, and were 5.1% and 48.2%, respectively, for diabetes. High education level, history of coronary heart disease (CHD), hypertension, being a current drinker, high body mass index (BMI), central obesity, hyper-triglyceride (hyper-TG), hyper-total cholesterol (hyper-TC), hypo-high density lipoprotein cholesterol (hypo-HDL-C), and abnormal aspartate aminotransferase (AST) were risk factors, while smoking and diabetes were protective factors of hyperuricemia in males. Older age, being single/divorced, having a high education level, hypertension, drinking tea, high BMI, central obesity, hyper-TG, hyper-TC, hypo-HDL-C, and abnormal alanine aminotransferase (ALT) were risk factors in females. The high prevalence of hyperuricemia but low prevalence of gout and common comorbidities in Zhuang adults may be due to a lag effect of lifestyle changes. Health education and health management should be strengthened to prevent the progression of comorbidities, considering the lag effect and low awareness rate.

Epidemiological characterization of Clonorchis sinensis infection in humans and freshwater fish in Guangxi, China.

BACKGROUND: Clonorchiasis is a widespread yet neglected foodborne disease with over 85% of all cases found in China. Guangxi province, located in southeastern China, ranks among the highest endemic provinces. We explore the epidemiological status and determinants of Clonorchis sinensis (C. sinensis) infection in humans and freshwater fish in Guangxi, China. METHODS: Data on C. sinensis infection in humans from January 2008 to December 2017were extracted from the China Information System for Disease Control and Prevention. An active surveillance of C. sinensis infection in fish was conducted in 2016-2017. County level data including potential environmental, social-economical and behavioral determinants was also collected. Univariate and multivariate logistic regression models were used to explore the determinants of C. sinensis infection in humans and fish. Simple and multiple zero-inflated Poisson regression models were fit to assess the associated factors of clonorchiasis in humans at the county level. RESULTS: Totally, 4526 C. sinensis cases were reported between 2008 and 2017, with an annual prevalencerate of 0.96/100,000 persons. Of 101 counties in Guangxi, 97 reported at least 1 case. Among 2,098 fish samples, 203 (9.7%) from 70 counties contained C. sinensis. The rate was higher in small fish including Pseudorasbora parva (45.3%), Misgurnus anguillicaudatus (41.2%), Hemicculter leuciclus (34.5%), unclassified small fishes (30.9%), Cyprinidae (20.0%), Cirrhinus molitorella (16.4%), Carassius auratus (13.6%) and Cyprinus carpio (13.3%), while it was lower in fish species that are usually used in preparing raw fish dishes including Ctenopharyngodon idellus (3.6%), Spinibarbus denticulatus (3.7%), Monopterus albus (6.4%), Cyprinus carpio (4.4%), Oreochromis mossambicus (3.3%) and Spualiobarbus Curriculus (6.6%). The C. sinensis infection in fish was only associated with fish species. The estimated human clonorchiasis prevalence at the county level was positively associated with raw fish consumption habits and certain rivers. CONCLUSIONS: Clonorchiasis is highly prevalent in both humans and freshwater fish in Guangxi. Environmental, social-economic and behavioral determinants contribute to the high prevalence as well as the significant differential distribution by county. Regular surveillance should be implemented for clonorchiasis to demonstrate the change in epidemiology and burden, which will benefit the design of interventions.

The Efficacy and Safety of Revefenacin for the Treatment of Chronic Obstructive Pulmonary Disease: A Systematic Review.

Background Revefenacin (REV) is a novel once-daily long-acting muscarinic antagonist (LAMA) in the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). This systematic review incorporating a dose-response meta-analysis aimed to assess the efficacy and safety of REV. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their inception to April 2020. We included randomized controlled trials (RCTs) which evaluated the efficacy and safety of REV in COPD patients. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. Outcomes consisted of the mean change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline, adverse events (AEs), and serious adverse events (SAEs). A dose-response meta-analysis using the robust error meta-regression method was conducted. We used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. Results Nine RCTs (3,121 participants) were included in this systematic review. The meta-analyses indicated that 175 µg/day REV could significantly improve the trough FEV1 (MD=143.67, 95%CI: 129.67 to 157.68; I2=96%; 809 participants; studies=4; low quality) without increasing the risk of AEs (OR=0.98, 95%CI: 0.81 to 1.18; I2=34%; 2,286 participants; studies=7; low quality) or SAEs (OR=0.89, 95%CI: 0.55 to 1.46; I2=0%; 2,318 participants; studies=7; very low quality) compared to placebo. Furthermore, the effect of REV in increasing trough FEV1 was dose-dependent with an effective threshold of 88 µg/day (R2 = 0.7017). Nevertheless, only very low-quality to low-quality evidence showed that REV at a dose of 175 µg/day was inferior to tiotropium regarding the long-term efficacy, and its safety profile was not superior to tiotropium or ipratropium. Conclusion Current evidence shows that REV is a promising option for the treatment of moderate to very severe COPD. Due to most evidence graded as low quality, further studies are required to compare the efficacy, long-term safety and cost-effectiveness between REV and other LAMAs in different populations. Clinical Trial Registration: [PROSPERO], identifier [CRD42020182793].

Ratio of the interferon-γ signature to the immunosuppression signature predicts anti-PD-1 therapy response in melanoma.

Immune checkpoint inhibitor (ICI) treatments produce clinical benefit in many patients. However, better pretreatment predictive biomarkers for ICI are still needed to help match individual patients to the treatment most likely to be of benefit. Existing gene expression profiling (GEP)-based biomarkers for ICI are primarily focused on measuring a T cell-inflamed tumor microenvironment that contributes positively to the response to ICI. Here, we identified an immunosuppression signature (IMS) through analyzing RNA sequencing data from a combined discovery cohort (n = 120) consisting of three publicly available melanoma datasets. Using the ratio of an established IFN-γ signature and IMS led to consistently better prediction of the ICI therapy outcome compared to a collection of nine published GEP signatures from the literature on a newly generated internal validation cohort (n = 55) and three published datasets of metastatic melanoma treated with anti-PD-1 (n = 54) and anti-CTLA-4 (n = 42), as well as in patients with gastric cancer treated with anti-PD-1 (n = 45), demonstrating the potential utility of IMS as a predictive biomarker that complements existing GEP signatures for immunotherapy.

SPARC suppresses lymph node metastasis by regulating the expression of VEGFs in ovarian carcinoma.

Lymph node metastasis is one of the most valuable determinants for the prognosis of ovarian cancer. However, the molecular mechanisms underlying lymphangiogenesis in ovarian cancer is still poorly understood. Secreted protein acidic and rich in cysteine (SPARC), a Ca2+-binding matricellular glycoprotein that modulates cell adhesion, migration and differentiation, is thought to play a decisive role in tumor metastasis. Vascular endothelial growth factor (VEGF)-C and VEGF-D contributes to tumor-associated lymphatic vessel growth, enhancing the metastatic spread of tumor cells to lymph nodes. The aim of the present study was to investigate the relationship among SPARC, VEGFs and lymph node metastasis in ovarian cancer. We found that SKOV3 cells expressed high-level SPARC, much more than SKOV3-PM4 cells (a subline with high directional lymphatic metastatic potentials established from the metastatic lymph node generated by human ovarian carcinoma cell line SKOV3 in nude mice) did at both mRNA and protein levels. A SPARC-overexpressed SKOV3-PM4 cell line was constructed and it was found that upregulation of SPARC expression suppressed the growth, migration and invasion of SKOV3-PM4 cells as well as markedly reduced the expression of VEGF-D at both mRNA and protein level by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. In 47 of ovarian malignant tissues, the expression of SPARC, VEGF-C and VEGF-D were determined by immunohistochemistry. Lymphatic microvessel density (LVD) and microvessel density (MVD) were evaluated by immunostaining with CD34 and D2-40 antibodies, respectively. We found that SPARC expression was significantly lower in tissues with lymph node metastasis as compared to tissues without lymph node metastasis. SPARC expression was inversely associated with the degree of malignancy and it had a negative correlation with VEGF-C expression, VEGF-D expression, LVD and MVD which were actually higher for advanced tumors than for non-advanced tumors. These results suggest SPARC might function as a tumor suppressor inhibiting angiogenesis and lymphangiogenesis in ovarian cancer by reducing the expression of VEGF-C and VEGF-D.

Impact of intra-operative cell salvage on blood coagulation in high-bleeding-risk patients undergoing cardiac surgery with cardiopulmonary bypass: a prospective randomized and controlled trial.

BACKGROUND: Intra-operative cell salvage (CS) was reported to have no impairment on blood coagulation in low-bleeding-risk cardiac surgery with cardiopulmonary bypass (CPB), but studies in high-bleeding-risk cardiac surgery are limited. The objective of this study is to evaluate the impact of CS on blood coagulation in high-bleeding-risk cardiac surgery with CPB. METHODS: One hundred and ten patients were randomly assigned to either with intra-operative CS group (Group CS) or without intra-operative CS group (Group C). Study endpoints included the incidence of impairment of blood coagulation during perioperative period (peri-op) and the incidence of adverse events during postoperative period (post-op). Peri-op was defined as the period from beginning of anesthesia (anesthesia induction) to 24 h after end of surgery. Post-op was defined as the period from the end of surgery to 24 h after end of surgery. The types of impairment of blood coagulation included heparin residual, coagulopathy due to low PLT, coagulopathy due to low FIB, coagulopathy due to low coagulation factors, hyperfibrinolytic. The sum of above five types was total impairment of blood coagulation. Adverse events included excessive bleeding, resternotomy, etc. RESULTS: The incidence of heparin residual measured both at the end of surgery and during post-op were significantly higher in Group CS than in Group C (15.09 vs 4.00, 13.21 vs 2.00 %; p = 0.024, 0.010, respectively). Similarly, the incidence of total impairment of blood coagulation at the end of surgery and during post-op were significantly higher in Group CS than in Group C (32.08 vs 18.00, 26.42 vs 12.00 %; p = 0.043, 0.040, respectively). The incidence of excessive bleeding during post-op was 32.08 % in Group CS compared with 16.00 % in Group C (p = 0.038). Intriguingly, CS was associated with a significantly increase in the relative risk ratios for heparin residual and excessive bleeding (p = 0.034, 0.049, respectively). CONCLUSIONS: Intra-operative CS could impair blood coagulation in the scenario of high-risk-bleeding cardiac surgery with CPB.

Human lymphatic endothelial cells contribute to epithelial ovarian carcinoma metastasis by promoting lymphangiogenesis and tumour cell invasion.

The microenvironment of a tumour is an important factor in ovarian cancer metastasis. The present study aimed to simulate the in vivo microenvironment of an ovarian carcinoma using a co-culture system consisting of human lymphatic endothelial cells (HLECs) and human ovarian carcinoma cells with directional high lymphatic metastasis (SKOV3-PM4s) in order to investigate the role of both cell types in ovarian carcinoma metastasis. The SKOV3-PM4s cultured in the HLEC-conditioned medium exhibited increased numbers of pseudopodia and mitotic figures, proliferated at a faster rate and exhibited enhanced invasion and migratory abilities. Furthermore, the HLECs cultured in SKOV3-PM4-conditioned medium exhibited significant morphological alterations and vacuolisation of the cytoplasm, as well as increased invasion, migratory and tube forming abilities. In addition, spontaneous fusion of the SKOV3-PM4s and HLECs was observed in the co-culture system using laser confocal microscopy. The gelatin zymography assay demonstrated that matrix metalloproteinase-2, which was downregulated in the SKOV3-PM4s, was upregulated in the co-culture system. The results of the present study suggested that the invasion ability of the SKOV3-PM4s was increased in the in vitro co-culture system of SKOV3-PM4 and HLECs. Therefore, alterations in the cell microenvironment may represent a novel strategy for ovarian cancer therapy.

Risk factors for measles in children younger than age 8 months: A case-control study during an outbreak in Guangxi, China, 2013.

BACKGROUND: Following a period (2009-2012) during which zero measles cases were reported, a measles outbreak occurred in 2013 in Bama County, Guangxi, China, that involved more than 100 children younger than age 8 months. We aimed to identify the pitfalls and risk factors while implementing the control measures. METHODS: An outbreak investigation and a case-control study was conducted among children younger than age 8 months. The serum specimens of the study subjects and their mothers were tested for measles immunoglobulin M and immunoglobulin G. RESULTS: The attack rate was 2.3/1,000 population. The median (interquartile range) age was 18.6 months (7.9-52.8 months). The coverage of 2-dose measles-containing vaccine was only 34%. The case-control study revealed 2 independent risk factors: low education level of main caregiver (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.31-6.22) and visiting a hospital 7-21 days before the date of symptoms onset (OR, 9.84; 95% CI, 4.27-22.67). The population attributable fraction of the latter was 52.8%. The mothers of the cases had nonsignificantly higher levels of immunoglobulin M and were significantly more likely to have protective levels of immunoglobulin G than those of the controls. This suggests a reactive rather than protective role of the antibody to the child's infection. CONCLUSIONS: In a near-elimination but low measles-containing vaccine coverage community, supplementary immunization activities should be emphasized for children and women who are potential future mothers. The minimum age of measles-containing vaccine should be further reduced. Hospital measles transmission must also be strictly prevented.

A Population-Based Acute Meningitis and Encephalitis Syndromes Surveillance in Guangxi, China, May 2007-June 2012.

OBJECTIVES: Acute meningitis and encephalitis (AME) are common diseases with the main pathogens being viruses and bacteria. As specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. In this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of AME, and identified factors that could be used to predict the etiologic agents. METHODS: A population-based AME syndrome surveillance system was set up in Guigang City, Guangxi, involving 12 hospitals serving the study communities. All patients meeting the case definition were investigated. Blood and/or cerebrospinal fluid were tested for bacterial pathogens using culture or RT-PCR and serological tests for viruses using enzyme-linked immunosorbent assays. Laboratory testing variables were grouped using factor analysis. Multinomial logistic regression was used to predict the etiology of AME. RESULTS: From May 2007 to June 2012, the annual incidence rate of AME syndrome, and disease specifically caused by Japanese encephalitis (JE), other viruses, bacteria and fungi were 12.55, 0.58, 4.57, 0.45 and 0.14 per 100,000 population, respectively. The top three identified viral etiologic agents were enterovirus, mumps virus, and JE virus, and for bacteria/fungi were Streptococcus sp., Cryptococcus neoformans and Staphylococcus sp. The incidence of JE and other viruses affected younger populations and peaked from April to August. Alteration of consciousness and leukocytosis were more likely to be caused by JE, bacteria and fungi whereas CSF inflammation was associated with bacterial/fungal infection. CONCLUSIONS: With limited predictive validity of symptoms and signs and routine laboratory tests, specific tests for JE virus, mumps virus and enteroviruses are required to evaluate the immunization impact and plan for further intervention. CSF bacterial culture cannot be omitted in guiding clinical decisions regarding patient treatment.

The efficacy, safety and cost-effectiveness of intra-operative cell salvage in high-bleeding-risk cardiac surgery with cardiopulmonary bypass: a prospective randomized and controlled trial.

OBJECTIVE: Intra-operative cell salvage (CS) was reported to be ineffective, safe and not cost-effective in low-bleeding-risk cardiac surgery with cardiopulmonary bypass (CPB), but studies in high-bleeding-risk cardiac surgery are limited. The objective of this study is to evaluate the efficacy, safety and cost-effectiveness of intra-operative CS in high-bleeding-risk cardiac surgery with CPB. METHODS: One hundred and fifty patients were randomly assigned to either with intra-operative CS group (Group CS) or without intra-operative CS group (Group C). Study endpoints were defined as perioperative allogeneic red blood cell (RBC) transfusion, perioperative impairment of blood coagulative function, postoperative adverse events and costs of transfusion-related. RESULTS: Both the proportion and quantity of perioperative allogeneic RBC transfusion were significantly lower in Group CS than that in Group C (p=0.0002, <0.0001, respectively). The incidence of residual heparin and total impairment of blood coagulative function in the 24 hours after surgery, the incidence of postoperative excessive bleeding, were significantly higher in Group CS than that in Group C (p=0.018, 0.042, 0.034, respectively). Cost of both allogeneic RBC transfusion and total allogeneic blood transfusion were significantly lower in Group CS than that in Group C (p<0.001, =0.002, respectively). Cost of total blood transfusion was significantly higher in Group CS than that in Group C (p =0.001). CONCLUSION: Intra-operative CS in high-bleeding-risk cardiac surgery with CPB is effective, generally safe, and cost-effective in developed countries but not in China.

[Characteristics change of the human directional highly lymphatic metastasis ovarian carcinoma cell and venous endothelial cell after establishment of their condition cultrue and co-culture cell system].

OBJECTIVE: To establish the condition cultrue cell system and co- culture cell system with SKOV3/PM4, HUVEC and to study the changes of their biological characteristics. METHODS: The cells of SKOV3/PM4 and HUVEC were labeled with green and red fluorescent respectively. The cell supernatant of SKOV3/PM4 and HUVEC were collected respectively as the condition medium (e.g: the cell supernatant of HUVEC cells was used as SKOV3/PM4 condition medium)and to establish the condition cultrue cell system and the co- culture cell system of the two cell lines. In the condition cultrue cell system, The morphological changes of cells were observed by HE staining to calculate the mitotic index. The ultrastructural changes of the two cells were observed by transmission electron microscopy (TEM). The growth curve of the cells was determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry was used to analyzed the cell cycles. In the co-culture cell system, the interaction of the two cells were detected by laser scanning confocal microscope (LSCM). The expression of matrix metalloproteinase- 2 (MMP- 2) and matrix metalloproteinase- 9 (MMP- 9) were detected by gelatin zymography. RESULTS: Compared with the single culture SKOV3/PM4, the cells which cultured in HUVEC condition medium showed the increase of pseudopodia and nuclear division, the mitotic index respectively were [(4.8 ± 0.8)%, (11.2 ± 0.3)%; P < 0.05]. The growth rate was significantly increased. In cell cycles, it showed the declined cell ratio of G0/G1 phase, respectively [(69.4 ± 3.6)%, (48.4 ± 4.6)%; P < 0.05] and the raised cell ratio of G2/M phase, respectively [(5.2 ± 1.6)%, (24.9 ± 2.2)%; P < 0.05]. Compared with the single culture HUVEC, the cells which cultured in SKOV3/PM4 condition medium showed the significant morphological change and vacuolization in the cytoplasm, Nuclear division was increased and the mitotic index respectively were [(2.7 ± 0.5)%, (5.7 ± 0.6)%; P < 0.05]. The growth rate was slightly declined. In cell cycles, it showed the raised cell ratio in G0/G1 phase, respectively [(51.4 ± 2.2)%, (79.0 ± 4.1)%; P < 0.05] and the declined cell ratio in G2/M phase, respectively [(19.1 ± 1.2)%, (3.3 ± 0.5)%; P < 0.05]. After co-culture for 48 hours, spontaneous fusion between SKOV3/PM4 and HUVEC cell was observed by the laser confocal microscope. Gelatin zymography assay showed that MMP-2 was not expressed in HUVEC cells, low-expressed in SKOV3/PM4 cells and high-expressed in the co-culture SKOV3/PM4+HUVEC cells. The expression of MMP-2 in co-culture SKOV3/PM4+HUVEC cells and SKOV3/PM4 cells respectively were 1 885 ± 84 and 1 209 ± 114 (P < 0.05). But there were no MMP-9 expression in HUVEC cells, SKOV3/PM4 cells, and the co- culture SKOV3/PM4+HUVEC. CONCLUSION: The characteristics of SKOV3/PM4 and HUVEC show significant changes after condition culture and co-culture, it may involve in the microenvironment of the cells and the intercellular crosstalk pathway.

Spatio-temporal clustering of hand, foot, and mouth disease at the county level in Guangxi, China.

BACKGROUND: Amid numerous outbreaks of hand, foot and mouth disease (HFMD) in Asia over the past decade, studies on spatio-temporal clustering are limited. Without this information the distribution of severe cases assumed to be sporadic. We analyzed surveillance data with onset dates between 1 May 2008 to 31 October 2013 with the aim to document the spatio-temporal clustering of HFMD cases and severe cases at the county level. METHODS: Purely temporal and purely spatial descriptive analyses were done. These were followed by a space-time scan statistic for the whole study period and by year to detect the high risk clusters based on a discrete Poisson model. RESULTS: The annual incidence rate of HFMD in Guangxi increased whereas the severe cases peaked in 2010 and 2012. EV71 and CoxA16 were alternating viruses. Both HFMD cases and severe cases had a seasonal peak in April to July. The spatio-temporal cluster of HFMD cases were mainly detected in the northeastern, central and southwestern regions, among which three clusters were observed in Nanning, Liuzhou, Guilin city and their neighbouring areas lasting from 1.2 to 2.5 years. The clusters of severe cases were less consistent in location and included around 40-70% of all severe cases in each year. CONCLUSIONS: Both HFMD cases and severe cases occur in spatio-temporal clusters. The continuous epidemic in Nanning, Liuzhou, Guilin cities and their neighbouring areas and the clusters of severe cases indicate the need for further intensive surveillance.