Bifunctional Squaramide-Catalyzed Oxidative Kinetic Resolution: Simultaneous Access to Axially Chiral Thioether and Sulfoxide.

Axially chiral thioethers and sulfoxides emerge as two pivotal classes of ligands and organocatalysts, which have remarkable features in the stereoinduction of various asymmetric transformations. However, the lack of easy methods to access such molecules with diverse structures has hampered their broader utilization. Herein, an oxidative kinetic resolution for sulfides using a chiral bifunctional squaramide as the catalyst with cumene hydroperoxide as the terminal oxidant is established. This asymmetric approach provides a variety of axially chiral thioethers as well as sulfoxides bearing both axial and central chirality, with excellent diastereo- and enantioselectivities. This catalytic system also successfully extends to the kinetic resolution of benzothiophene-based sulfides. Preliminary mechanism investigation indicates that the multiple hydrogen bonding interactions between the bifunctional squaramide catalyst and substrates play a crucial role in determining the enantioselectivity and reactivity.

circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations.

circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.

Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6/11/16/18/31/33/45/52/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial.

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.

Safety and immunogenicity of an Escherichia coli-produced 9-valent human papillomavirus L1 virus-like particle vaccine (types 6/11/16/18/31/33/45/52/58) in healthy adults: an open-label, dose-escalation phase 1 clinical trial.

Background: A safe and highly efficacious Escherichia coli (E. coli)-produced HPV 16/18 bivalent vaccine has been prequalified by the World Health Organization. Here, we conducted a single-center, open-label, dose-escalation phase 1 clinical trial to evaluate the safety and immunogenicity of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. Method: Twenty-four eligible volunteers aged 18-45 years were enrolled in January 2019 in Dongtai, China and received 0.5 mL (135 µg) or 1.0 mL (270 µg) of the candidate vaccine with a 0/1/6-month dose-escalation schedule. Local and systemic adverse events (AEs) occurring within 30 days after each vaccination and serious adverse events (SAEs) occurring within 7 months were recorded. Blood samples from each participant were collected before and 2 days after the first and third vaccinations to determine changes in laboratory parameters. Serum IgG and neutralizing antibody (nAb) levels against each HPV type at month 7 were analyzed (ClinicalTrials.gov: NCT03813940). Findings: The incidences of total AEs in the 135 µg and 270 µg groups were 66.7% and 83.3%, respectively. All AEs were mild or moderate, and no SAEs were reported. No clinically significant changes were found in paired blood indices before or after any of the vaccinations. All the participants in the per-protocol set except for two who failed to seroconvert for HPV 11 or 58 in the 135 µg group seroconverted at month 7 for both IgG and nAbs. Interpretation: The candidate E. coli-produced 9vHPV vaccine has been preliminarily proven to be well tolerated and immunogenic, which encourages further studies in large cohorts with a wider age range. Funding: This study was supported by the National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Fujian Province Health and Education Joint Research Program, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax Biotechnology Co., Ltd.

Abietane diterpenoids from Orthosiphon wulfenioides with NLRP3 inflammasome inhibitory activity.

Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC50 values ranging from 0.23 to 3.43 µM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1ß down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis.

Enantioselective synthesis of α-amino ketones through palladium-catalyzed asymmetric arylation of α-keto imines.

Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.

Use of GLP1RAs and occurrence of respiratory disorders: A meta-analysis of large randomized trials of GLP1RAs.

OBJECTIVES: No large sample studies have been designed to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP1RAs) in the primary and secondary prevention of respiratory disorders. We aimed at evaluating the relationship between use of GLP1RAs and occurrence of 12 kinds of respiratory disorders. METHODS: Large randomized placebo-controlled trials of GLP1RAs were included. We conducted meta-analysis using random effects model and measured heterogeneity using I2 . Treatment effect was presented as risk ratio (RR) and 95% confidence interval (CI). RESULTS: Seven trials including 55 922 participants were included in meta-analysis. The occurrence rates of various respiratory disorders were low, with the minimum of 0.02% (pulmonary fibrosis) and the maximum of 2.31% (pneumonia). Although not reaching statistical significance, GLP1RAs versus placebo showed the reduced trends in the risks of nine kinds of respiratory disorders including pneumonia (RR 0.89, 95% CI 0.78-1.01), squamous cell carcinoma of lung (SCCL; RR 0.55, 95% CI 0.25-1.21), asthma (RR 0.82, 95% CI 0.51-1.32), and chronic obstructive pulmonary disease (COPD; RR 0.89, 95% CI 0.73-1.10), but the increased trend in interstitial lung disease (ILD; RR 1.89, 95% CI 0.87-4.08). GLP1RAs had neutral effects on two other respiratory disorders. Heterogeneity in any meta-analysis was absent or low. CONCLUSION: GLP1RAs show the reduced trends in the risks of nine kinds of respiratory disorders (eg, pneumonia, SCCL, asthma, and COPD), but the increased trend in the risk of ILD. However, these findings need to be validated by further studies due to the low incidence rates of all the respiratory disorders.

Impact of metabolic syndrome on short-term outcome of carotid revascularization: a large sample size study in Chinese population.

BACKGROUND: Metabolic syndrome (MetS) is relatively common worldwide and an important risk factor for cardiovascular diseases. It is closely linked to arterial stiffness of the carotid artery. However, the association of MetS with the safety of carotid revascularization has been rarely studied. The aim of this study was to observe the current status of MetS and its components in Chinese carotid revascularized patients, and investigate the impact on major adverse clinical events (MACEs) after carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: From January 2013 to December 2017, patients undergoing CEA or CAS in the Neurosurgery Department of Xuanwu Hospital were retrospectively recruited. The changes in prevalence of MetS and each component with time were investigated. The primary outcome was 30-day post-operative MACEs. Univariable and multivariable analyses were performed to identify the impact of MetS on CEA or CAS. RESULTS: A total of 2068 patients who underwent CEA (766 cases) or CAS (1302 cases) were included. The rate of MetS was 17.9%; the prevalence rate of MetS increased with time. The occurrence rate of MACEs in CEA was 3.4% (26 cases) and in CAS, 3.1% (40 cases). There was no statistical difference between the two groups (3.4% vs. 3.1%, P = 0.600). For CEA patients, univariate analysis showed that the MACE (+) group had increased diabetes history (53.8% vs. 30.9%, P = 0.014) and MetS (34.6% vs. 15.8%, P = 0.023). For CAS patients, univariate analysis showed that the MACE (+) group had increased coronary artery disease history (40.0% vs. 21.6%, P = 0.006) and internal carotid artery tortuosity (67.5%% vs. 37.6%, P < 0.001). Furthermore, the MACE (+) group had higher systolic blood pressure (143.38 ±â€Š22.74 vs. 135.42 ±â€Š17.17 mmHg, P = 0.004). Multivariable analysis showed that the influencing factors for MACEs in CEA included history of diabetes (odds ratio [OR] = 2.345; 95% confidence interval [CI] = 1.057-5.205; P = 0.036) and MetS (OR = 2.476; 95% CI = 1.065-5.757; P = 0.035). The influencing factors for MACEs in CAS included systolic blood pressure (OR = 1.023; 95% CI = 1.005-1.040; P = 0.010), coronary artery disease (OR = 2.382; 95% CI = 1.237-4.587; P = 0.009) and internal carotid artery tortuosity (OR = 3.221; 95% CI = 1.637-6.337; P = 0.001). CONCLUSIONS: The prevalence rate of MetS increased with time in carotid revascularized patients. MetS is a risk for short-term MACEs after CEA, but not CAS.

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.

BACKGROUND: This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli. METHODS: This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90µg, 60µg, or 30µg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed. RESULTS: All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60µg (GMT=10,548) and 90µg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30µg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified. CONCLUSION: The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60µg dosage formulation was selected for further investigation for efficacy. CLINICAL TRIALS REGISTRATION: NCT01356823.

Long-term efficacy of a hepatitis E vaccine.

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined. METHODS: In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years. RESULTS: During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups. CONCLUSIONS: Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

[Effect of strategy of control and prevention of intestinal nematodiasis in Dongtai City, Jiangsu Province].

OBJECTIVE: To explore the strategy of intestinal nematodiasis control in Dongtai City, Jiangsu Province. METHODS: The strategy of mass drug administration assisted with health education was applied in Dongtai City, which was a high endemic area of intestinal nematodiasis, and then the health education and promotion assisted with drug administration of focus population and other integrated control measures, such as the improvement of drinking water, lavatories, and environment, was applied to consolidate the achievement. RESULTS: The infection rate of intestinal nematodes reduced from 79.97% in 1989 to 6.30% in 1999, and the infection rates of hookworm, Ascaris lumgricoides and Trichuris trichura reduced to 3.31%, 0.60% and 2.57%, respectively, achieving the standard of intestinal nematodiasis control. In 2002, the infection rate of intestinal nematodes reduced to 3.73%, and the infection rates of hookworm, Ascaris lumgricoides and Trichuris trichura reduced to 2.46%, 0.20% and 1.08%, respectively, achieving the standard of effective intestinal nematodiasis control. The infection rate of intestinal nematodes was kept less than 1% after 2004. CONCLUSION: The integrated strategy of intestinal nematodiasis control in Dongtai City is effective and valuable for promotion in high endemic areas of intestinal nematodiasis.

Epidemiology of zoonotic hepatitis E: a community-based surveillance study in a rural population in China.

BACKGROUND: Hepatitis E is caused by two viral genotype groups: human types and zoonotic types. Current understanding of the epidemiology of the zoonotic hepatitis E disease is founded largely on hospital-based studies. METHODS: The epidemiology of hepatitis E was investigated in a community-based surveillance study conducted over one year in a rural city in eastern China with a registered population of 400,162. RESULTS: The seroprevalence of hepatitis E in the cohort was 38%. The incidence of hepatitis E was 2.8/10,000 person-years. Totally 93.5% of the infections were attributed to genotype 4 and the rest, to genotype 1. Hepatitis E accounted for 28.4% (102/359) of the acute hepatitis cases and 68.9% (102/148) of the acute viral hepatitis cases in this area of China. The disease occurred sporadically with a higher prevalence during the cold season and in men, with the male-to-female ratio of 3∶1. Additionally, the incidence of hepatitis E increased with age. Hepatitis B virus carriers have an increased risk of contracting hepatitis E than the general population (OR = 2.5, 95%CI 1.5-4.2). Pre-existing immunity to hepatitis E lowered the risk (relative risk  = 0.34, 95% CI 0.21-0.55) and reduced the severity of the disease. CONCLUSIONS: Hepatitis E in the rural population of China is essentially that of a zoonosis due to the genotype 4 virus, the epidemiology of which is similar to that due to the other zoonotic genotype 3 virus.

Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine: an open-label phase I clinical trial.

An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate.

[Endemic situation of malaria in Dongtai City, 1999-2013].

OBJECTIVE: To understand the characteristics of malaria endemic situation in Dongtai City, from 1999 to 2013. METHODS: The data of diagnosed malaria cases and related information of prevention and treatment were collected and analyzed with the epidemiological method. RESULTS: From 1999 to 2013, there were 27 malaria cases in total, and among which 2 cases were local-infected with Plasmodium vivax, 10 cases were imported P. vivax infections, 13 cases were imported P. falciparum infections, and 1 case was a mixed infections (P. falciparum, P. vivax and P. ovale). The imported cases accounted for 92.59% and local-infected cases accounted for 7.41%. There were no local-infected cases after 2003, and all the cases were overseas-imported. The main first-diagnosis points were town hospitals and village health stations, accounting for 33.33% and 33.33% respectively. Totally 62.96% of cases visited the clinic in 1 day after the attacking, the median of time-interval from the attacking to visiting the clinic was 1 day, the median of time-interval from the attacking to confirmed diagnosis was 3 days, and the max time from the attacking to confirmed diagnosis was 33 days. CONCLUSION: The malaria cases are mainly imported cases in Dongtai City from 1999 to 2013, and therefore, the key of eliminating malaria should be the monitoring of the retuned exporting labors.

[Effects of steaming and baking on content of alkaloids in Aconite Lateralis Radix (Fuzi)].

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.

Immunogenicity and safety of hepatitis E vaccine in healthy hepatitis B surface antigen positive adults.

A recombinant hepatitis E vaccine, Hecolin, has been proven safe and effective in healthy adults. As hepatitis B surface antigen (HBsAg) positive individuals have a higher risk of poor prognosis after super-infection with hepatitis E virus (HEV), the safety and immunogenicity of Hecolin in this population should be assessed. The present study is an extending analysis of data from a large randomized controlled clinical trial of Hecolin. Healthy participants (n = 14,065) without current or previous evidence of chronic liver disease were randomized to receive Hecolin or placebo (hepatitis B vaccine) and donated their blood samples before vaccination and subsequently over 31 mo. Most of the adverse events were mild and comparable between participants with and without baseline hepatitis B surface antigen (HBsAg). No vaccine-related serious adverse events were reported. Rates of serious adverse events in HBsAg (+) or HBsAg (-) participants were also comparable between both groups. Almost all participants in the Hecolin group seroconverted to anti-HEV one month after full vaccination. The antibody response rates and levels were similar in HBsAg (+) and HBsAg (-) participants (98.38%, 19.32 Wu/mL vs. 98.69%, 19.00 Wu/mL). The two-year antibody dynamics of HBsAg (+) participants overlapped perfectly with those of HBsAg (-) participants. In conclusion, the safety and immunogenicity of Hecolin for HBsAg (+) adults is very similar to that for the general population.

[Surveillance after schistosomiasis transmission interrupted in sandy areas].

The surveillance after schistosomiasis transmission interrupted in sandy areas showed that the schistosomiasis endemic did not occur locally, but the factors of transmission still existed. Therefore, we should continue to enhance the management of mobile population and snail control, and explore appropriate measures for schistosomiasis monitoring.

Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial.

BACKGROUND: Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. METHODS: Healthy adults aged 16-65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 microg of purified recombinant hepatitis E antigen adsorbed to 0.8 mg aluminium hydroxide suspended in 0.5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov, number NCT01014845. FINDINGS: 11,165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56,302) or placebo (n=56,302). 48,693 (86%) participants in the vaccine group and 48,663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100.0% (95% CI 72.1-100.0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. INTERPRETATION: HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16-65 years. FUNDING: Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.

Effects of dietary supplementation of certain nutrients on maze performance and biochemical indices in mice after exposure to high +Gz.

OBJECTIVE: To explore the possible effects of nutritional supplements on brain function as reflected by Water Maze test performance in mice after +Gz exposure. METHOD: Mice were arranged into control group (group A), +Gz group without nutritional supplementation (group B) and +Gz plus nutritional supplementation group (group C). Each group contains 12 mice. Mice in group A were not exposed to +Gz while mice in both group B and group C were exposed to 8 min + 10 Gz. Distilled water was gavaged to group B mice 3 h before +Gz exposure. On the day before +Gz exposure pyridoxol fortified water was given and 3 h before exposure mixed amino acids solution were gavaged to group C mice. Water Maze test was done and scores were recorded in all groups. After the Water Maze test was completed, blood was collected through the eyes for serum amino acid determinations and brain tissue was collected by decollation for monoamine determination and gamma-glutamyl transferase (GGT) activity evaluation. RESULT: After +Gz exposure, longer completion time and more mistakes were observed in Water Maze test in group B as compared with group A and a trend of improvement in group C was noticed. The ratio of brain 5-HT to dopamine (DA) was significantly reduced in group C as compared with group B. Gamma glutamyl transferase (GGT) activity in brain tissue in group C and group B increased significantly. CONCLUSION: High sustained +Gz exposure significantly reduces Water Maze test performance in mice (longer completion time and more mistakes). It seems that there is a trend of improvement in Water Maze performance in mice in dietary nutritional supplementation group, which might be due to significant reduction in ratio of brain 5-HT to DA in mice with nutritional supplementation.

[Effects of nutritional intervention on brain functions and its related biochemical indexes in mice exposed to high +Gy].

OBJECTIVE: To study the effects of nutritional intervention on changes of monoamines in rats brain, certain amino acids in rats serum and maze behaviors caused by high +Gy exposure. METHOD: The mice were arranged into control group (Group A), +Gy group (Group B) and +Gy nutritional intervention group (group C). Group A was not exposed to +Gy. Both Group B and group C were exposed to +10 Gy for 8 min. Three hours before +Gy exposure distilled water was given to mice in group B by gavage. The day before exposure pyridoxal fortified water was given and 3 h before exposure mixed amino acids solution were given by gavage to group C. Maze test scores were recorded for all groups. After the maze test was completed, blood was collected through the eyes for serum amino acids and brain tissue was collected by decollation for monoamines and gamma-glutamyl transferase (GGT) activity determinations. RESULT: After +Gy exposure maze test scores and brain NE concentrations decreased and abnormal behaviors were found. While other monoamine transmitters increased significantly. In group C maze behaviors improved and biochemical changes induced by +Gy exposure alleviated. CONCLUSION: High +Gy exposure can induce changes of neural transmitters coming from nutritional metabolites in central nervous system. As a result, brain functions are affected. Nutritional intervention can alleviate this negative effect to some extent.