Lactobacillus paracasei R3 Alleviates Tumor Progression in Mice with Colorectal Cancer.

Lactobacillus paracasei (L. paracasei), a common probiotic lactobacillus, has important functions in the food industry and human health. However, different strains of L. paracasei inevitably show differences in activity and colonization resistance, leading to differentiation in their functions, as well as their physical or chemical properties. The purpose of this study was to evaluate the characteristics of L. paracasei R3 (L.p R3) isolated from healthy human feces and determine whether the criteria for edible probiotics is met. The hemolysis type, biofilm-forming ability, antibiotic susceptibility, toxicity, and effective activity of L.p R3 were determined by establishing its probiotic activity traits in vitro and in vivo. The results showed that L.p R3 had a moderate biofilm formation ability, was sensitive to 11 antibiotics, was resistant to eight antibiotics, and was not hemolytic. The culture characteristics, morphology, and biochemical responses of the strain were consistent with the seed batch characteristics. In toxicity assays, L.p R3-fed mice showed no abnormalities in body weight, growth, or various organs. Additionally, L.p R3 was found to be effective in the prevention and treatment of colorectal cancer. In conclusion, our results revealed that L.p R3 has potential value as an edible probiotic without toxic side effects and alleviated the tumor progression of colorectal cancer in mice.

Sinisan ameliorates colonic injury induced by water immersion restraint stress by enhancing intestinal barrier function and the gut microbiota structure.

CONTEXT: Sinisan (SNS) has been used to treat psychosomatic diseases of the digestive system. But little is known about how SNS affects water immersion restraint stress (WIRS). OBJECTIVE: To study the effects of SNS on colonic tissue injury in the WIRS model. MATERIALS AND METHODS: Forty-eight Kunming (KM) mice were randomized into 6 groups (n = 8): The control and WIRS groups receiving deionized water; the SNS low-dose (SL, 3.12 g/kg/d), SNS middle-dose (SM, 6.24 g/kg/d), SNS high-dose (SH, 12.48 g/kg/d), and diazepam (DZ, 5 mg/kg/d) groups; each with two daily administrations for 5 consecutive days. The 5 treatment groups were subjected to WIRS for 24 h on day 6. The effects of SNS on colon tissue injury caused by WIRS were assessed by changes in colon histology, inflammatory cytokines, brain-gut peptides, and tight junction (TJ) proteins levels. 16S rRNA gene sequencing was used to detect the regulation of the gut microbiota. RESULTS: SNS pretreatment significantly reduced TNF-α (0.75- to 0.81-fold), IL-6 (0.77-fold), and IFN-γ (0.69-fold) levels; and increased TJ proteins levels, such as ZO-1 (4.06- to 5.27-fold), claudin-1 (3.33- to 5.14-fold), and occludin (6.46- to 11.82-fold). However, there was no significant difference between the levels of substance P (SP) and vasoactive intestinal peptide (VIP) in the control and WIRS groups. SNS regulated the composition of gut microbiota in WIRS mice. CONCLUSION: The positive effects of SNS on WIRS could provide a theoretical basis to treat stress-related gastrointestinal disorders.

Immunodomination of Serotype-Specific CD4+ T-Cell Epitopes Contributed to the Biased Immune Responses Induced by a Tetravalent Measles-Vectored Dengue Vaccine.

Dengue is an emerging mosquito-borne disease, and the use of prophylactic vaccines is still limited. We previously developed a tetravalent dengue vaccine (rMV-TDV) by a recombinant measles virus (MV) vector expressing envelope protein domain III (ED3). In this study, we used dengue-susceptible AG129 mice to evaluate the protective and/or pathogenic immune responses induced by rMV-TDV. Consistent with the previous study, rMV-TDV-immunized mice developed a significant neutralizing antibody response against all serotypes of DENV, as well as a significant IFN-γ response biased to DENV-3, compared to the vector controls. We further demonstrated that this DENV-3-specific IFN-γ response was dominated by one CD4+ T-cell epitope located in E349-363. After DENV-2 challenge, rMV-TDV-immunized mice showed a significantly lower viremia and no inflammatory cytokine increase compared to the vector controls, which had an ~100 times higher viremia and a significant increase in IFN-γ and TNF-α. As a correlate of protection, a robust memory IFN-γ response specific to DENV-2 was boosted in rMV-TDV-immunized mice after challenge. This result suggested that pre-existing DENV-3-dominated T-cell responses did not cross-react, but a DENV-2-specific IFN-γ response, which was undetectable during immunization, was recalled. Interestingly, this recalled T-cell response recognized the epitope in the same position as the E349-363 but in the DENV-2 serotype. This result suggested that immunodomination occurred in the CD4+ T-cell epitopes between dengue serotypes after rMV-TDV vaccination and resulted in a DENV-3-dominated CD4+ T-cell response. Although the significant increase in IgG against both DENV-2 and -3 suggested that cross-reactive antibody responses were boosted, the increased neutralizing antibodies and IgG avidity still remained DENV-2 specific, consistent with the serotype-specific T cell response post challenge. Our data reveal that immunodomination caused a biased T-cell response to one of the dengue serotypes after tetravalent dengue vaccination and highlight the roles of cross-reactive T cells in dengue protection.

Systematic Review of Health-Related Quality of Life in Patients with Pulmonary Arterial Hypertension.

BACKGROUND: The increasing survival of patients with pulmonary arterial hypertension (PAH) has shifted attention towards the disease burden that PAH imposes on patients and healthcare systems. Most studies emphasize epidemiology and medications, while large observational studies reporting on the health-related quality of life (HRQOL) of patients with PAH are lacking. OBJECTIVE: Our objective was to study the HRQOL of patients with PAH and to summarize the factors that influence it. METHODS: We conducted systematic literature searches in English (PubMed, Web of Knowledge, ScienceDirect and OVID) and Chinese (China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP and SinoMed) databases to identify studies published from 2000 to 2015 assessing the HRQOL of patients with PAH. Search results were independently reviewed and extracted by two reviewers. RESULTS: Of 3392 records identified in the initial search, 20 eligible papers (19 English, 1 Chinese) were finally included. Studies used a range of instruments; the generic 36-item Short Form Survey (SF-36) was the most widely used, and the disease-specific Cambridge Pulmonary Hypertension Outcome Survey (CAMPHOR) was the second mostly widely used. Mean HRQOL scores assessed via the SF-36 (physical component summary [PCS] 25.4-80.1; mental component summary [MCS] 33.2-76.0) and CAMPHOR (symptom scores 3.1-17; total HRQOL 2.8-12.6; activity scores 3.8-18.1) varied across studies, reporting decreased HRQOL in patients. Mental health (depression, anxiety, stress), physical health (exercise capacity, symptoms) and medical therapies were reported to affect HRQOL. CONCLUSION: We found that PAH places a substantial burden on patients, particularly in terms of HRQOL; however, the paucity of large observational studies in this area requires the attention of researchers, especially in China.

The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection.

Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine.

Systematic Review of the Economic Burden of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), as a life-threatening disease with no efficient cure, may impose a tremendous economic burden on patients and healthcare systems. However, most existing studies have mainly emphasised epidemiology and medications, while large observational studies reporting on the economic burden are currently lacking. OBJECTIVES: To review and evaluate evidence on the costs of PAH and the cost effectiveness of PAH treatments, and to summarise the corresponding cost drivers. METHODS: Systematic literature searches were conducted in English-language databases (PubMed, Web of Science, ScienceDirect) and Chinese-language databases (China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP) to identify studies (published from 2000 to 2014) assessing the costs of PAH or the cost effectiveness of PAH treatments. The search results were independently reviewed and extracted by two reviewers. Costs were converted into 2014 US dollars. RESULTS: Of 1959 citations identified in the initial search, 19 papers were finally included in this analysis: eight on the economic burden of PAH and 11 on economic evaluation of PAH treatments. The economic burden on patients with PAH was rather large, with direct healthcare costs per patient per month varying from $2476 to $11,875, but none of the studies reported indirect costs. Sildenafil was universally reported to be a cost-effective treatment, with lower costs and better efficacy than other medications. Medical costs were reported to be the key cost drivers. CONCLUSION: The economic burden of patients with PAH is substantial, while the paucity of comprehensive country-specific evidence in this area and the lack of reports on indirect costs of PAH warrant researchers' concern, especially in China.

The Immunodominance Change and Protection of CD4+ T-Cell Responses Elicited by an Envelope Protein Domain III-Based Tetravalent Dengue Vaccine in Mice.

Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3) is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4), we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost). A significant serotype-dependent IFN-γ or IL-4 response was observed in mice immunized with either the DNA or protein vaccine. The IFN-γ response was dominant to DENV-1 to 3, whereas the IL-4 response was dominant to DENV-4. Although the similar IgG titers for the four serotypes were observed in mice immunized with the tetravalent vaccines, the neutralizing antibody titers varied and followed the order of 2 = 3>1>4. Interestingly, the lower IFN-γ response to DENV-4 is attributable to the immunodominance change between two CD4+ T-cell epitopes; one T-cell epitope located at E349-363 of DENV-1 to 3 was more immunogenic than the DENV-4 epitope E313-327. Despite DENV-4 specific IFN-γ responses were suppressed by immunodominance change, either DENV-4-specific IFN-γ or neutralizing antibody responses were still recalled after DENV-4 challenge and contributed to virus clearance. Immunization with the prime-boost elicited both IFN-γ and neutralizing antibody responses and provided better protection than either DNA or protein immunization. Our findings shed light on how ED3-based tetravalent dengue vaccines sharpen host CD4 T-cell responses and contribute to protection against dengue virus.

Impact of China's Public Hospital Reform on Healthcare Expenditures and Utilization: A Case Study in ZJ Province.

BACKGROUND: High drug costs due to supplier-induced demand (SID) obstruct healthcare accessibility in China. Drug prescriptions can generate markup-related profits, and the low prices of other medical services can lead to labor-force underestimations; therefore, physicians are keen to prescribe drugs rather than services. Thus, in China, a public hospital reform has been instituted to cancel markups and increase service prices. METHODS: A retrospective pre/post-reform study was conducted in ZJ province to assess the impact of the reform on healthcare expenditures and utilization, ultimately to inform policy development and decision-making. The main indicators are healthcare expenditures and utilization. RESULTS: Post-reform, drug expenditures per visit decreased by 8.2% and 15.36% in outpatient and inpatient care, respectively; service expenditures per visit increased by 23.03% and 27.69% in outpatient and inpatient care, respectively. Drug utilization per visit increased by 5.58% in outpatient care and underwent no significant change in inpatient care. Both were lower than the theoretical drug-utilization level, which may move along the demand curve because of patient-initiated demand (PID); this indicates that SID-promoted drug utilization may decrease. Finally, service utilization per visit increased by 6% in outpatient care and by 13.10% in inpatient care; both were higher than the theoretical level moving along the demand curve, and this indicates that SID-promoted service utilization may increase. CONCLUSION: The reform reduces drug-prescription profits by eliminating drug markups; additionally, it compensates for service costs by increasing service prices. Post-reform, the SID of drug prescriptions decreased, which may reduce drug-resource waste. The SID of services increased, with potentially positive and negative effects: accessibility to services may be promoted when physicians provide more services, but the risk of resource waste may also increase. This warrants further research. It is recommended that comprehensive measures that control SID and promote physician enthusiasm be carried out concurrently.

Comparison of glucose lowering effect of metformin and acarbose in type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: Metformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus recommended by international guidelines. However, little information exists comparing it with acarbose which is also commonly used in China. This study expanded knowledge by combining direct and indirect evidence to ascertain the glucose lowering effects of both drugs. METHODS: PubMed (1980- December 2013) and China National Knowledge Infrastructure databases (1994-January 2014) were systematically searched for eligible randomized controlled trials from Chinese and English literatures. Meta-analysis was conducted to estimate the glucose lowering effects of metformin vs. acarbose, or either of them vs. common comparators (placebo or sulphonylureas), using random- and fixed-effect models. Bucher method with indirect treatment comparison calculator was applied to convert the summary estimates from the meta-analyses into weighted-mean-difference (WMD) and 95% confidence intervals (CIs) to represent the comparative efficacy between metformin and acarbose. RESULTS: A total of 75 studies were included in the analysis. In direct comparison (8 trials), metformin reduced glycosylated hemoglobin (HbA1c) by 0.06% more than acarbose, with no significant difference (WMD,-0.06%; 95% CI, -0.32% to 0.20%). In indirect comparisons (67 trials), by using placebo and sulphonylureas as common comparators, metformin achieved significant HbA1c reduction than acarbose, by -0.38% (WMD,-0.38%, 95% CI, -0.736% to -0.024%) and -0.34% (WMD, -0.34%, 95% CI, -0.651% to -0.029%) respectively. CONCLUSION: The glucose lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin is a little better by indirect comparison. This implies that the effect of metformin is at least as good as acarbose's.

A systematic review of the direct economic burden of type 2 diabetes in china.

BACKGROUND: Type 2 diabetes is associated with acute and chronic complications and poses a large economic, social, and medical burden on patients and their families as well as society. OBJECTIVE: This study aims to evaluate the direct economic burden of type 2 diabetes in China. DATA SOURCE: systematic review on cost of illness, health care costs, direct service costs, drug costs, and health expenditures in relation to type 2 diabetes was conducted up to 2014 using databases such as Pubmed; EBSCO; Elsevier ScienceDirect, Web of Science; and a series of Chinese databases, including Wanfang Data, China National Knowledge Infrastructure (CNKI), and the China Science and Technology Journal Database. Factors influencing hospitalization and drug fees were also identified. STUDY ELIGIBILITY CRITERIA: (1) estimation of the direct economic burden including hospitalization and outpatient cost of type 2 diabetes patients in China; (2) evaluation of the factors influencing the direct economic burden. Articles only focusing on the cost-effectiveness analysis of diabetes drugs were excluded. RESULTS: The direct economic burden of type 2 diabetes has increased over time in China, and in 2008, the direct medical cost reached $9.1 billion, Both outpatient and inpatient costs have increased. Income level, type of medical insurance, the level of hospital care, and type and number of complications are primary factors influencing diabetes related hospitalization costs. Compared to urban areas, the direct non-medical cost of type 2 diabetes in rural areas is significantly greater. CONCLUSIONS: The direct economic burden of type 2 diabetes poses a significant challenge to China. To address the economic burden associated with type 2 diabetes, measures need to be taken to reduce prevalence rate and severity of diabetes and hospitalization cost.

Cost-Minimization Analysis of Metformin and Acarbose in Treatment of Type 2 Diabetes.

BACKGROUND: Metformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus (T2DM) per international guidelines with proven efficacy, safety, and cost-effectiveness. However, little information comparing it with acarbose exists. OBJECTIVE: To study the cost-effectiveness of metformin and acarbose-two extensively adopted agents-in treating T2DM. METHODS: Cost-minimization analysis was conducted on the assumption that metformin and acarbose have equivalent clinical effectiveness. The cost of treatment was detected and evaluated from a payer's perspective. In sensitivity analyses, several clinical scenarios were developed according to clinical practices and physicians' prescribing behaviors in China. RESULTS: Metformin can save annual treatment costs by 39.87% to 40.97% compared with acarbose. Under a wide range of assumptions on utilization profile and physician prescribing behavior, it saves costs by 19.83% to 40.97% in patients whose weight is 60 kg or less and by 39.87% to 70.49% in patients whose weight is more than 60 kg, which corroborates the results that metformin is more cost-effective than acarbose. CONCLUSIONS: Metformin appears to provide better value for money than does acarbose. Findings from this study are consistent with those from previous studies that metformin is undoubtedly the first choice in the management of T2DM, with significant glucose-lowering effects and low treatment costs.

[Study on willingness to participate and willingness to pay for hypothetical industrial injury insurance scheme].

OBJECTIVE: To investigate workers' willingness to participate and wiliness to pay for a hypothetical industrial injury insurance scheme, to analyze the influential factors, and to provide information for policy making of the government. METHODS: Multistage cluster sampling was used to select subjects: In the first stage, 9 small, medium, orlarge enterprises were selected fromthree cities (counties) in Zhejiang province, China, according to the level of economic development, transportation convenience, and cooperation of government agencies; in the second stage, several workshops were randomly selected from each of the 9 enterprises. Face-to-face interviews among all workers in the workshops were conducted by trained interviewers using a pre-designed questionnaire. RESULTS: It was found that 73.87% (2095) of all workers were willing to participate in the hypothetical work injury insurance scheme and to pay 2.21% of monthly wage (51.77 yuan) on average, and more than half of the workers were willing to pay less than 1%of monthly wage (35 yuan). Of the 741 workers who were not willing to participate, 327 thought that the premium should be borne by the state or enterprises, instead of individuals, and others were not willing to participate because of low income, unstable job, or poor understanding of the hypothetical industrial injury insurance scheme. Logistic regression analysis showed that workers with higher education levels, longer length of services, longer weekly working time, or more knowledge of occupational diseases showed higher willingness to participate in the scheme; workers who were exposed to physical hazards, had health records, or had participated in the existing medical insurance or industrial injury insurance were more willing to participate. Multiple linear regression analysis showed that with increasing average monthly wage, weekly working time, and self?health evaluation, the proportion of workers with willingness to pay increased; however, with increasing work intensity and awareness of occupational disease, the proportion of workers with willingness to pay decreased. The workers who were not covered by the industrial injury insurance paid more than those covered by the industrial injury insurance. CONCLUSION: The hypothetical industrial injury insurance scheme increased the applicability and advantage of independent third-party running and lifetime insurance, which significantly increased the workers' willingness to participate in or to pay for the insurance scheme. Therefore, the industrial injury insurance can be improved in these aspects to promote workers' willingness to participate in and to pay for the insurance scheme. This conclusion provided a reference for the solution of delayed or shirking corporate responsibility for paying the premium.

A poorly neutralizing IgG2a/c response elicited by a DNA vaccine protects mice against Japanese encephalitis virus.

We demonstrated previously that immunization with a DNA vaccine expressing the Japanese encephalitis virus (JEV) envelope (E) protein conferred a high level of protection through a poorly neutralizing antibody response. Here, we further investigated the role of the IgG subclass in this antibody-dependent protection using cytokine co-immunization and cytokine-deficient mice. A significant difference in IgG2a/c but not IgG1 was observed between mice that survived or died following a lethal challenge. Correspondingly, the IgG2a/c response and protection increased in IL-4-deficient mice but decreased in IFN-γ-deficient mice, highlighting the importance of IgG2a/c. In addition, the restoration of protection and E-specific IgG2a/c production in IFN-γ-deficient mice by a T helper (Th) type 1-biased intramuscular immunization suggested that IgG2a/c but not IFN-γ was the major component for protection. The failure of protection against a direct intracranial challenge indicated that IgG2a/c-mediated protection was restricted to outside the central nervous system. Consistent with this conclusion, passive transfer of E-specific antisera conferred protection only pre-exposure to JEV. Therefore, our data provided evidence that the IgG subclass plays an important role in protection against JEV, particular in poorly neutralizing E-specific antibodies, and Th1-biased IgG2a/c confers better protection than Th2-biased IgG1 against JEV.

[The coverage of work injury insurance and its affecting factors in Zhejiang province, China].

OBJECTIVE: In China, the coverage rate of work injury insurance was 23.2%in 2011, which was far lower than expected. The factors affecting the insurance's enrollment has very little known. This paper aims to study the existing coverage of work injury insurance scheme and its influencing factors. METHODS: The data were collected from 2 836 workers who came from 9 industries in three cities of Zhejiang province using face-to-face questionnaire interview. RESULTS: Of these 2836 workers, the work injury insurance coverage was 50.1%, and 29.6% were not sure if they were covered or not. The results showed that the awareness of occupational disease and industrial injury insurance was helpful in increasing the coverage rate. Besides, the logistic regression analysis showed that in certain circumstances working population shared higher coverage of work injury insurance. For examples, male workers with local household registration and longer working years; people who had been informed about occupational risk factors, and thus gained more training on the issue; people who had exposed to occupational hazards or involved in administrative duties; and people who had already insured by a medical insurance scheme. In the contrary, the heavier family burden with longer working hours per week they needed, the lower possibility they joined the insurance scheme. CONCLUSIONS: The coverage of work injury insurance is higher than native average level but much lower than the average international level. The awareness of occupational disease and injury insurance was closely associated with the coverage of work injury insurance. Therefore, it is imperative to popularize the knowledge on OHS for migrant workers, as well as to reinforce the supervision and management of the issue would have been an effective way to elevate the coverage rate of work injury insurance.

A preliminary analysis of the effect of the new rural cooperative medical scheme on inpatient care at a county hospital.

BACKGROUND: China in 2009 committed to reach universal health coverage by promoting three forms of health insurance; NCMS for the rural population, UEBMI for formally employed urban residents and URBMI for other urban residents. NCMS has expanded to near universal coverage in rural China since launching in 2003. The objective of this study aimed to assess the effect of NCMS on inpatient care utilization from 2003 to 2012 at Longyou county hospital, Zhejiang province. METHODS: The research was conducted at Longyou county, Zhejiang province. All registered inpatient admissions from January 1, 2003, to June 30, 2012, were included in the study. The PLSQL Developer software was used to select the interesting variables in the hospital information database and saved in an Excel 2003 file. The interesting variables included the patients' general information (name, gender, age, payment method), discharge diagnosis, length of hospital stay, and expenditure (total expenditure and out-of-pocket payment). Two common diseases (coronary arteriosclerotic disease and pneumonia) were selected as tracer conditions. RESULTS: 292,400 rural residents were enrolled in the Longyou county NCMS by 2011, 95.4% of the eligible population. A total of 145,744 inpatient admissions were registered from 1 January 2003 to 30 June 2012. The proportion of inpatients covered by NCMS increased from 30.3% in 2004 to 54.2% in 2012 while the proportion of inpatients covered by UEBMI increased from 7.7% in 2003 to 14.7% in 2012. The average expenditure for UEBMI insured inpatients was higher than the average for NCMS insured inpatients, although the gap was narrowing. The average length of hospital stay increased every year for all inpatients, but was higher for UEBMI inpatients than for NCMS insured inpatients. For both tracer conditions the results were similar to the above findings. CONCLUSIONS: NCMS has improved coverage height for its enrollees and resulted in increased cost of care per inpatient admission at the county hospital. However, wide differences persist between the two insurance systems in coverage height. Both systems are associated with increasing lengths of stay and rising cost per inpatient admission. We found that around 30% of inpatients were not covered by any of the two public health insurance systems, which calls for further studies.

[Study on optimal model of hypothetical work injury insurance scheme].

OBJECTIVE: To explore an optimal model of hypothetical work injury insurance scheme, which is in line with the wishes of workers, based on the problems in the implementation of work injury insurance in China and to provide useful information for relevant policy makers. METHODS: Multistage cluster sampling was used to select subjects: first, 9 small, medium, and large enterprises were selected from three cities (counties) in Zhejiang Province, China according to the economic development, transportation, and cooperation; then, 31 workshops were randomly selected from the 9 enterprises. Face-to-face interviews were conducted by trained interviewers using a pre-designed questionnaire among all workers in the 31 workshops. RESULTS: After optimization of hypothetical work injury insurance scheme, the willingness to participate in the scheme increased from 73.87%to 80.96%; the average willingness to pay for the scheme increased from 2.21% (51.77 yuan) to 2.38% of monthly wage (54.93 Yuan); the median willingness to pay for the scheme increased from 1% to 1.2% of monthly wage, but decreased from 35 yuan to 30 yuan. The optimal model of hypothetical work injury insurance scheme covers all national and provincial statutory occupational diseases and work accidents, as well as consultations about occupational diseases. The scheme is supposed to be implemented worldwide by the National Social Security Department, without regional differences. The premium is borne by the state, enterprises, and individuals, and an independent insurance fund is kept in the lifetime personal account for each of insured individuals. The premium is not refunded in any event. Compensation for occupational diseases or work accidents is unrelated to the enterprises of the insured workers but related to the length of insurance. The insurance becomes effective one year after enrollment, while it is put into effect immediately after the occupational disease or accident occurs. CONCLUSION: The optimal model of hypothetical work injury insurance scheme actually realizes cross-regional mobility of workers, minimizes regional differences, and embodies the fairness. The proposed model will, to some extent, protect the rights and interests of enterprises, as well as the healthy rights and interests of workers when they are unemployed.

A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates.

We have previously demonstrated that vaccination with a subunit dengue vaccine containing a consensus envelope domain III with aluminum phosphate elicits neutralizing antibodies against all four serotypes of dengue virus in mice. In this study, we evaluated the immunogenicity of the subunit dengue vaccine in non-human primates. After vaccination, monkeys that received the subunit vaccine with aluminum phosphate developed a significantly strong and long-lasting antibody response. A specific T cell response with cytokine production was also induced, and this correlated with the antibody response. Additionally, neutralizing antibodies against serotype 2 were detected in two of three monkeys. The increase in serotype-2-specific antibody titers and avidity observed in these two monkeys suggested that a serotype-2-biased antibody response occurs. These data provide evidence that a protective neutralizing antibody response was successfully elicited in non-human primates by the dengue subunit vaccine with aluminum phosphate adjuvant.

SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx.

Small ubiquitin-like modifier (SUMO) modification is emerging as an important control in transcription regulation. Here, we show that CREB-binding protein (CBP), a versatile transcriptional coactivator for numerous transcription factors in response to diverse signaling events, can be modified by SUMO-1 at lysine residues 999, 1034, and 1057 both in vitro and in vivo. Mutation of the SUMO acceptor lysine residues either individually or in combination enhanced CBP transcriptional activity, and expression of a SUMO protease SENP2 potentiated the transcriptional activity of CBP wild-type but not its sumoylation mutant, indicating that SUMO modification negatively regulates CBP transcriptional activity. Furthermore, we demonstrated an interaction of SUMO-1-modified CBP with the transcriptional corepressor Daxx and an essential role of Daxx in mediating SUMO-dependent transcriptional regulation of CBP through histone deacetylase 2 recruitment. Together, our findings indicate that SUMO modification and subsequent recruitment of Daxx represent a previously undescribed mechanism in modulating CBP transcriptional potential.

NuMA expression and function in mouse oocytes and early embryos.

Nuclear mitotic apparatus protein (NuMA), originally described as a nuclear protein, is an essential component in the formation and maintenance of mitotic spindle poles. In this study, we analyze the expression pattern and function of NuMA in mouse oocytes and early embryos. In germinal vesicle-stage oocytes, NuMA was detected both at the centrosome and in the nucleus. However, after nuclear maturation and extrusion of the first polar body, NuMA was concentrated at the broad meiotic spindle poles and at cytasters (centers of cytoplasmic microtubule asters) of mature metaphase II oocytes. Cold-induced depolymerization of microtubules appeared to disassociate NuMA foci from the cytoplasmic cytasters. During fertilization, NuMA was relocated into the re-formed male and female pronuclei. Microinjection of anti-NuMA antibody into 1 of 2 cells of 2-cell-stage embryos inhibited normal cell division. These results suggest that NuMA might play an important role in cell division during early embryonic mitosis.