Changing Epidemiology of Hepatitis A in China: Evidence From Three National Serological Surveys and the National Notifiable Disease Reporting System.

BACKGROUND AND AIMS: China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine. APPROACH AND RESULTS: Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after >10 years of private sector vaccination, HepA coverage was <30% among children <5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was >90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts. CONCLUSIONS: The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.

Detection system of the lobster eye telescope with large field of view.

The lobster eye telescope is promising for large-field x ray imaging in astronomy. The special structure of the lobster eye system makes the focal plane a sphere, resulting in detector defocus when the field is large. In this study, we established a model based on the principle of lobster eye imaging and simulated the imaging at different image distances. The results reveal the relationship between the defocus and position accuracy and angular resolution. To ensure the optical performance of the large field lobster eye telescope, we propose a detection system design method using multiple detectors stitched together to form a spherical-like surface and apply it to the development of the Einstein Probe/wide-field x ray telescope (EP/WXT) submodule. About 70% of the detection area is out of focus within 0.5 mm. The scanning image of the integrated WXT submodule shows good uniformity of the point spread function (PSF) for various incident angles, and the effect of defocus on imaging is acceptable.

Active case finding with case management: the key to tackling the COVID-19 pandemic.

COVID-19 was declared a pandemic by WHO on March 11, 2020, the first non-influenza pandemic, affecting more than 200 countries and areas, with more than 5·9 million cases by May 31, 2020. Countries have developed strategies to deal with the COVID-19 pandemic that fit their epidemiological situations, capacities, and values. We describe China's strategies for prevention and control of COVID-19 (containment and suppression) and their application, from the perspective of the COVID-19 experience to date in China. Although China has contained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and nearly stopped indigenous transmission, a strong suppression effort must continue to prevent re-establishment of community transmission from importation-related cases. We believe that case finding and management, with identification and quarantine of close contacts, are vitally important containment measures and are essential in China's pathway forward. We describe the next steps planned in China that follow the containment effort. We believe that sharing countries' experiences will help the global community manage the COVID-19 pandemic by identifying what works in the struggle against SARS-CoV-2.

Inhibition of glycolysis ameliorate arthritis in adjuvant arthritis rats by inhibiting synoviocyte activation through AMPK/NF-кB pathway.

OBJECTIVE: This study aimed to evaluate glycolysis inhibitor which can effectively ameliorate arthritis by inhibiting synoviocyte activation through AMPK/NF-кB pathway in AA rats. METHODS: Adjuvant arthritis (AA) rats were treated with 2-deoxyglucose (2-DG), glycolysis inhibitor. HE staining and radiological Examination were used for histopathology analysis and evaluation of joint destruction. HKII expression was quantified by immunostaining. Proliferation and migration of synoviocytes were assessed by synovicyte scores of joint, CCK8 and transwell assay. Inflammatory factors and levels of AMPK, p65 and IκBα were quantified by ELISA analysis and WB. RESULTS: We observed that HKII expression was positively correlated with synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction, and glycolysis inhibitor reduces the joint swelling degree, alleviates bone destruction, inhibits the proliferation and migration of synoviocyte, and reduces secretory function of synoviocytes in AA rats. In addition, we investigated that glycolysis inhibitor may inhibit activation of the NF-κB signaling pathway by activating the AMPK pathway. CONCLUSION: This study suggests the involvement of energy metabolism in the pathological inflammation process in RA joints. Glycolysis inhibitors might, therefore, provide an opportunity for therapeutic intervention.

Self-motivated medical care-seeking behaviors and disease progression in a community-based cohort of chronic hepatitis B virus-infected patients in China.

BACKGROUND: To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up. METHODS: We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments. RESULTS: Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0-1.6), those in 0-19-year old (aRR = 1.5, 95% CI:1.1-2.1), 20-39-year old (aRR = 2.2, 95% CI:1.7-3.0) and 40-49-year old (aRR = 1.5, 95% CI:1.1-2.0), and persons with insurance of the type Urban residents' basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7-3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4-2.6). Patients were more likely to receive antiviral treatment if they were 20-39-year old (aRR = 0.4, 95% CI:0.3-0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1-6.3) or NRCMS (aRR = 3.0, 95% CI:1.3-6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4-3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively. CONCLUSION: The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

[Synergistic Effect of 2-deoxy-D-glucose Combined with Hydroxycamptothecin on Apoptosis of Breast Cancer Cells].

OBJECTIVE: To investigate the effect of 2-deoxy-d-glucose (2-DG) combined with hydroxycamptothecin (HCPT) on anti-tumor activity of breast cancer cells and its mechanism. METHODS: MDA-MB-231 and MCF-7 breast cancer cells were incubated with varying concentrations of 2-DG (0, 1.25, 2.5, 5, 10, 20 mmol/L), HCPT(0, 5, 10, 20, 40 µmol/L) and 2-DG (5 mmol/L) combined with HCPT. Cell viability was measured using the MTT assay; Propidium iodide (PI) detected the apoptosis of MDA-MB-231 cells by 5 mmol/L 2-DG, 10 µmol/L HCPT alone or in combination; MDA-MB-231 cells were treated with 2-DG (0, 2.5, 5, 10, 20 mmol/L) and the level of ATP was detected by ATP kit; the expression of Akt, p-Akt, Bcl-2/Bax, PARP, Caspase-8 and Caspase-3 proteins in MDA-MB-231 cells were measured by Western blot assay. RESULTS: The combination of 2-DG (5 mmol/L) and HCPT had a synergistic effect. The 48 h combination index (CI < 1) was higher than that of the single-use group (P < 0.05). At the same time, the combination of the two drugs inhibits the phosphorylation of Akt protein and increases the activation of Caspase-3 protein, thereby increasing the cleavage of PARP proteins. CONCLUSION: The combination of 2-DG and HCPT can synergistically induce the apoptosis of breast cancer cells, which may be caused by inhibiting the energy generation of tumor cells, inhibiting the phosphorylation of Akt protein and enhancing the activity of caspase-3 protein.

Downregulation of monocarboxylate transporter 1 inhibits the invasion and migration through suppression of the PI3K/Akt signaling pathway in human nasopharyngeal carcinoma cells.

Monocarboxylate transporter 1 (MCT1) has been reported to be correlated wtih decreased survival and advanced stage of progression in a series of human tumor cells and primary cancers. Specifically, MCT1 has been documented to be involved in tumor progression, including invasion and migration. Here, we investigated the mechanism and effect of regulation of MCT1 on invasion and migration of nasopharyngeal carcinoma (NPC) cells. In the study, we firstly demonstrated that the expression of MCT1 in CNE2Z cells was obviously higher than that in HNE1 cells. Downregulation of MCT1 inhibited the invasion and migration in CNE2Z cells, upregulated the expression of E-cadherin, TIMP (tissue inhibitor of metalloproteinase)-2 and TIMP-1, and suppressed the expression of matrix metalloproteinases (MMP)-9 and MMP-2. Correspondingly, upregulation of MCT1 enhanced the invasive and migratory potential in HNE1 cells, increased the expression of MMP-9 and MMP-2, and downregulated the expression of E-cadherin, TIMP-2 and TIMP-1. The mechanistic study demonstrated that the effect of MCT1 might be correlated with PI3K/Akt signaling pathway. LY294002, a PI3K inhibitor, increased the inhibition of invasion and migration mediated by downregulation of MCT1 in CNE2Z cells. These findings collectively suggested that MCT1 might act as a new regulator to improve invasion and migration of NPC cells and be correlated with activating the PI3K/Akt pathway.

Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China.

China's hepatitis B virus (HBV) prevention policy has been evaluated through nationally representative serologic surveys conducted in 1992 and 2006. We report results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in the context of program policy. The 2014 survey used a 2-stage sample strategy in which townships were selected from 160 longstanding, nationally representative, county-level disease surveillance points, and persons 1-29 years of age were invited to participate. The 2014 sample size was 31,713; the response rate was 83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of age, the decline was 97%. China's HBV prevention program, targeted toward interrupting perinatal transmission, has been highly successful and increasingly effective. However, this progress must be sustained for decades to come, and elimination of HBV transmission will require augmented strategies.

Shikonin induces necroptosis by reactive oxygen species activation in nasopharyngeal carcinoma cell line CNE-2Z.

Shikonin, a natural small agent, has shown inhibitory effect in many kinds of cells, which increases intracellular reactive oxygen species (ROS) level and causes mitochondrial injury. In this study, shikonin showed good inhibitory effect on nasopharyngeal carcinoma CNE-2Z cells in vivo and vitro. The results presented here revealed that ROS levels increased markly after shikonin treated. The electron microscopy displays the change in ultrastructure of CNE-2Z cells after treatment for shikonin, which indicated that shikonin induced necroptosis. Shikonin-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), while the activity was unaffected by the caspase inhibitor z-VAD-fmk. Furthermore, we have demonstrated that the activation of receptor-interacting kinase (RIP) led to necroptosis. Meanwhile, shikonin also significantly inhibited tumor growth in a CNE-2Z xenograft mouse model. Taken together, shikonin induced CNE-2Z cells death by producing ROS as a necroptosis inducer. It could serve as a new therapeutic agent for treating CNE-2Z cells.

Impact of the Ebola outbreak on routine immunization in western area, Sierra Leone - a field survey from an Ebola epidemic area.

BACKGROUND: Since March 2014, the Ebola Virus Disease (EVD) outbreak in West Africa disrupted health care systems - especially in Guinea, Liberia and Sierra Leone - with a consequential stress on the area's routine immunization programs. To address perceived decreased vaccination coverage, Sierra Leone conducted a catch-up vaccination campaign during 24-27 April 2015. We conducted a vaccination coverage survey and report coverage estimates surrounding the time of the EVD outbreak and the catch-up campaign. METHODS: We selected 3 villages from each of 3 communities and obtained dates of birth and dates of vaccination with measles vaccine (MV) and the 3rd dose of Pentavalent vaccine (Pentavalent3) of all children under 4 years of age in the 9 selected villages. Vaccination data were obtained from parent-held health cards. We calculated the children's MV and Pentavalent3 coverage rates at 3 time points, 1 August 2014, 1 April 2015, and 1 May 2015, representing coverage rates before the EVD outbreak, during the EVD outbreak, and after the Maternal and Child Health Week (MCHW) catch-up campaign. RESULTS: The final sample size was 168 children. MV coverage among age-eligible children was 71.3% (95% confidence interval [CI]: 62.1% - 80.4%) and 45.7% (95% CI: 29.2% - 62.2%) before and during the outbreak of EVD, respectively, and was 56.8% (95% CI: 40.8% - 72.7%) after the campaign. Pentavalent3 coverage among age-eligible children was 79.8% (95% CI: 72.6% - 87.0%) and 40.0% (95% CI: 22.5% - 57.5%) before and during the outbreak of EVD, and was 56.4% (95% CI: 39.1% - 73.4%) after the campaign. CONCLUSIONS: Coverage levels of MV and Pentavalent3 were low before the EVD outbreak and decreased further during the outbreak. Although the MCHW catch-up campaign increased coverage levels, coverage remained below pre-outbreak levels. High-quality supplementary immunization activities should be conducted and routine immunization should be strengthened to address gaps in immunity among children in this EVD-affected area.

[Autophagy inhibitor 3-methyladenine enhances the sensitivity of nasopharyngeal carcinoma cells to chemotherapy and radiotherapy].

OBJECTIVE: To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.
 METHODS: Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS)-related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot.
 RESULTS: Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly reduced cell viability and enhanced the apoptosis in the DDP (6.00 µmol/L), 4.00 Gy IR or TM (1.00 µmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA.
 CONCLUSION: 3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells.

Mechanisms underlying 3-bromopyruvate-induced cell death in colon cancer.

3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT /protein Kinase B signaling in breast cancer cells. Here we found that 3BP can also induce colon cancer cell death by necroptosis and apoptosis at the same time and concentration in the SW480 and HT29 cell lines; in the latter, autophagy was also found to be a mechanism of cell death. In HT29 cells, combined treatment with 3BP and the autophagy inhibitor 3-methyladenine (3-MA) exacerbated cell death, while viability in 3BP-treated cells was enhanced by concomitant treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and the necroptosis inhibitor necrostatin (Nec)-1. Moreover, 3BP inhibited tumor growth in a SW480 xenograft mouse model. These results indicate that 3BP can suppress tumor growth and induce cell death by multiple mechanisms at the same time and concentration in different types of colon cancer cell by depleting cellular energy stores.

[Analysis of the hepatitis B report data on pilot surveillance in 200 counties in China, 2013].

OBJECTIVE: To analyze the information of the supplementary card for hepatitis B and the laboratory confirmed result of immunoglobulin M antibody to hepatitis B virus (HBV) Core Antigen (anti-HBc IgM) for the suspected acute hepatitis B to evaluate the hepatitis B report data on pilot surveillance. METHODS: 200 counties were established in China for hepatitis B pilot surveillance and 63 641 cases were reported. We added a supplementary card in National Notificable Disease Reporting System (NNDRS) and all the reported hepatitis B cases in NNDRS were required to fill the supplementary card. Venous blood 5 ml was collected and a confirmed test of anti-HBc IgM was made for suspected acute hepatitis B. We made confirmed diagnosis for the suspected acute hepatitis B according to the supplementary card information of the reporting card and the confirmed test result of anti-HBc IgM. RESULTS: 63 641 hepatitis B cases were reported in 200 hepatitis B pilot surveillance counties in 2013. Among 1 723 cases which were filled with the HBsAg positive within six months in supplementary card, 735 cases were reported as chronic hepatitis B, the proportion was 42.66%. Among 4 582 cases which were filled with anti-HBc IgM positive in supplementary card, 2 436 cases were reported as acute hepatitis B, the proportion was 53.16%. 1 829 cases were reported as chronic hepatitis B, the proportion was 39.92%. The validity cases of the information for liver puncture and the HBV surface antigen (HBsAg) transform during the recovery period in supplementary cards for all the reporting cases were 579 and 4 961, and the rate were 0.91% and 7.80%, respectively. 4 302 suspected acute cases were made confirmed diagnosis, and 1 197 cases (27.82%) were confirmed acute and 2 590 cases (60.20%) were confirmed chronic. CONCLUSION: Clinical doctors failed to make full use of the information of supplementary cards to make classification diagnose for hepatitis B. Suspected acute hepatitis B with anti-HBc IgM positive should be pay attention to follow up and further distinguish acute or chronic hepatitis B according to the HBsAg transform.

Literature review to identify evidence of secondary transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains to unvaccinated subjects.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants and young children. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains leading to clinical disease was not well evaluated in the pivotal clinical trials, and only a few case reports have been described in the literature. METHODS: We performed a systematic literature review to investigate secondary transmission of RV5 strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers, and other resources (i.e., conference papers with full text) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles based on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 strain transmission as outcomes. Other study or publication types were excluded, such as pre-clinical studies, interventional studies and case reports. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used, and study quality was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess the risk of bias. RESULTS: The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of the NOS or JBI checklist, respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms, but all symptoms were attributed to other clinical conditions. CONCLUSIONS: We found no evidence of horizontal transmission of RV5 strains to unvaccinated infants in a context of a limited amount and the descriptive nature of the identified studies.

Diminazene Ameliorates Neuroinflammation by Suppression of Astrocytic miRNA-224-5p/NLRP3 Axis in Alzheimer's Disease Model.

Purpose: ACE2/Ang(1-7)/Mas Receptor, the momentous component of the renin-angiotensin system, has been shown to be involved in Alzheimer's disease (AD). We had previously found that enhancing brain ACE2 activity ameliorated cognitive impairment and attenuated brain neuroinflammation in SAMP8 mice, an animal model of AD. However, the exact mechanism of action of Diminazene (DIZE) has not been revealed. Methods: APP/PS1 mice were injected intraperitoneally with DIZE. Cognitive functions, neuronal and synaptic integrity, and inflammation-related markers were assessed by Morris water maze, Nissl staining, Western blotting and ELISA, respectively. Since astrocytes played a crucial role in AD-related neuroinflammation whilst miRNAs were reported to participate in modulating inflammatory responses, astrocytes of APP/PS1 mice were then isolated for high-throughput miRNAs sequencing to identify the most differentially expressed miRNA following DIZE treatment. Afterward, the downstream pathway of this miRNA in the anti-inflammatory action of DIZE was investigated using primary astrocytes. Results: The results showed that DIZE alleviated cognitive impairment and neuronal and synaptic damage in APP/PS1 mice. Simultaneously, DIZE suppressed the secretion of pro-inflammatory cytokines and the expression of NLRP3 inflammasome. Importantly, miR-224-5p was significantly up-regulated in the astrocytes of APP/PS1 mice treated by DIZE, and NLRP3 is one of the targets of miR-224-5p. Upregulation of miR-224-5p inhibited the expression of NLRP3 in Aß1-42-stimulated cells, whereas miR-224-5p downregulation reversed this effect. Furthermore, the inhibition of miR-224-5p could reverse the inhibitory effect of DIZE on astrocytic NLRP3 inflammasome. Conclusion: These findings firstly suggested that DIZE could inhibit astrocyte-regulated neuroinflammation via miRNA-224-5p/NLRP3 pathway. Furthermore, our study reveals the underlying mechanism by which DIZE suppresses neuroinflammatory responses in AD mice and uncovers the potential of DIZE in AD treatment.

AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.

The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer's disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1ß and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10. Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice. These findings highlight the brain AngIV/PI3K/AKT axis as a potential target for the treatment of AD.

Angiotensin-(1-7) Analogue AVE0991 Modulates Astrocyte-Mediated Neuroinflammation via lncRNA SNHG14/miR-223-3p/NLRP3 Pathway and Offers Neuroprotection in a Transgenic Mouse Model of Alzheimer's Disease.

OBJECTIVE: Emerging evidence suggests that brain angiotensin-(1-7) (Ang-(1-7)) deficiency contributes to the pathogenesis of Alzheimer's disease (AD). Meanwhile, our previous studies revealed that restoration of brain Ang-(1-7) levels provided neuroprotection by inhibition of inflammatory responses during AD progress. However, the potential molecular mechanisms by which Ang-(1-7) modulates neuroinflammation remain unclear. MATERIALS AND METHODS: APP/PS1 mice were injected intraperitoneally with AVE0991 (a nonpeptide analogue of Ang-(1-7)) once a day for 30 consecutive days. Cognitive functions, neuronal and synaptic integrity, and inflammation-related markers were assessed. Since astrocytes played a crucial role in AD-related neuroinflammation whilst long noncoding RNAs (lncRNAs) were reported to participate in modulating inflammatory responses, astrocytes of APP/PS1 mice were isolated for high-throughput lncRNA sequencing to identify the most differentially expressed lncRNA following AVE0991 treatment. Afterward, the downstream pathways of this lncRNA in the anti-inflammatory action of AVE0991 were investigated using primary astrocytes. RESULTS: AVE0991 rescued spatial cognitive impairments and alleviated neuronal and synaptic damage in APP/PS1 mice. The levels of Aß1-42 in the brain of APP/PS1 mice were not affected by AVE0991. By employing high-throughput lncRNA sequencing, our in vitro study demonstrated for the first time that AVE0991 suppressed astrocytic NLRP3 inflammasome-mediated neuroinflammation via a lncRNA SNHG14-dependent manner. SNHG14 acted as a sponge of miR-223-3p while NLRP3 represented a direct target of miR-223-3p in astrocytes. In addition, miR-223-3p participated in the AVE0991-induced suppression of astrocytic NLRP3 inflammasome. CONCLUSION: Our results suggest that Ang-(1-7) analogue AVE0991 inhibits astrocyte-mediated neuroinflammation via SNHG14/miR-223-3p/NLRP3 pathway and offers neuroprotection in APP/PS1 mice. These findings reveal the underlying mechanisms by which Ang-(1-7) inhibits neuroinflammation under AD condition and uncover the potential of its nonpeptide analogue AVE0991 in AD treatment.

Protective effect of vaccinating infants with a 5 µg recombinant yeast-derived hepatitis B vaccine and the need for a booster dose in China.

In 2002, China integrated hepatitis B vaccine (HepB) into its Expanded Program on Immunization (EPI) using HepB vaccine containing 5 µg of antigen. Although not recommended nationally, there was a common clinical practice in China of screening children for anti-HBs antibody level and giving a booster dose to HBV surface antigen (HBsAg)-negative children with non-protective anti-HBs antibody levels. We report an evaluation of the protective effectiveness of the 5 µg HepB vaccine and the serological response to the booster dose. We used data from a 2014 hepatitis B serological survey to determine HBsAg positivity and anti-HBs antibody levels among children who received and did not receive a booster dose. We determined HepB coverage from the Children Immunization Information Management System (CIIMS). We obtained and analyzed reports of acute Hepatitis B (AHB) during 2008-2014 obtained from the National Notifiable Disease Reporting System (NNDRS). The HBsAg-positive rate among children who had not received a booster dose was 0.41%, and did not increase with age (i.e., time since infant immunization). The anti-HBs positivity rate among the 6% of children who received a booster dose (88.41%) was higher than among those who had not received a booster (60.85%); anti-HBs antibody levels declined with age regardless of booster dose status. There was no statistically significant difference in HBsAg positivity between children who received a booster dose and those who did not. The AHB incidence among children born between 2002 and 2007 did not increase with age. Use of routine 5 µg HepB vaccine was not associated with an increase in AHB or of HBsAg positivity by time since vaccination, providing supportive evidence that individuals vaccinated with the 5 µg HepB vaccine do not need a booster dose. Although a booster dose was associated with increases in anti-HBs antibody levels, our study provided no evidence to support the need for this clinical practice. We should continue to strengthen serological monitoring of children, especially for those born to HBsAg positive mothers.

Epidemiological distribution of hepatitis B virus genotypes in 1-29-year-olds in the mainland of China.

BACKGROUND: To analyze the epidemiological distribution of Hepatitis B virus (HBV) genotype in the mainland of China following the implementation of effective preventive measures. METHODS: Five hundred and seventeen HBsAg-positive subjects aged 1-29 years surveyed in the 2014 national HBV sero-survey in the mainland of China were enrolled in the study. The full-length HBV genome was obtained by PCR amplification and sequencing. The HBV genotype was determined by phylogenetic analysis. Combined with questionnaire information, HBV genotype distribution was analyzed. RESULTS: Of the 517 HBsAg-positive subjects, 369 (71.4%) were included in the analysis. HBV genotypes found were B (45.0%), C (36.6%), D (6.0%), C/D (9.8%), B/C (2.2%), and I (0.5%). Geographic differences in HBV genotype were significant for seven regions. Three serotypes were found: adw (47.2%), adr (35.5%), and ayw (17.3%). B2 (43.9%) and C2 (25.2%) were the two major subgenotypes. The predominant genotypes differed between the Han group and the other ethnic groups. No statistical differences in genotype distribution were found by gender, age group, or hepatitis B (HepB) vaccination history. CONCLUSION: The prevalence of HBV genotype B was higher than that of genotype C with subgenotypes B2 and C2 endemic in 1-29-year-olds in the mainland of China, after HBV prevalence has reduced significantly due to the implementation of preventive measures. HepB vaccination or other factors did not interfere with HBV genotype distribution. The surveillance of HBV genotype was essential for responding to the potential changes and impact on the preventive policies in the future.

Changes in the epidemiology of hepatitis A in three socio-economic regions of China, 1990-2017.

BACKGROUND: Hepatitis A (HepA) vaccination and economic transitions can change the epidemiology of HepA. China's Gross Domestic Product (GDP) per capita was known to be inversely associated with the incidence of HepA, but a deeper understanding of the epidemiology of HepA in different socio-economic regions is lacking. We compare the changing epidemiology of HepA in three socioeconomic-geographic regions of China. METHODS: We obtained data on all HepA cases reported through the National Notifiable Disease Reporting System and assessed trends and changes in age-specific incidence rates by age quartile and season. We categorized the country into three regions, the sequential years into five era, compared the incidence, quartile age, seasonal intensity and coverage of HepA of the three regions. Linear regression was performed to analyse trends in incidence of HepA and to analyse the association between coverage and incidence. RESULTS: The annual mean incidences of HepA in the eastern, central, and western regions decreased from 63.52/100 000, 50.57/100 000 and 46.39/100 000 in 1990-1992 to 1.18/100 000, 1.05/100 000 and 3.14/100 000 in 2012-2017, respectively. Decreases in incidence were seen in all age groups in the three regions; the incidence was highest (9.3/100 000) in the youngest age group (0-4 years) of the western region, while in the central region, the age group with the highest incidence changed from 0 to 9 years to adults ≥60 years old. In 2017, the median age of HepA cases was 43 years (Q1-Q3: 33-55), 47 years (Q1-Q3: 32-60) and 33 years (Q1-Q3: 9-52) in the eastern, central, and western provinces, respectively. Seasonal peaks became smaller or were nearly elimination nationwide, but seasonality persisted in some provinces. After the Expanded Program on Immunization (EPI) included HepA vaccine into the routine schedule in 2007, HepA coverage increased to > 80% in the three regions and was negatively association with the HepA incidence. CONCLUSION: The incidence of HepA decreased markedly between 1990 and 2017. A socioeconomic inequity in coverage of HepA vaccine was almost eliminated after HepA vaccine was introduced into China's EPI system, but inequity in incidence still existed in lower socio-economic developed region.