Aging-induced MCPH1 translocation activates necroptosis and impairs hematopoietic stem cell function.

DNA damage contributes to the aging of hematopoietic stem cells (HSCs), yet the underlying molecular mechanisms are not fully understood. In this study, we identified a heterogeneous functional role of microcephalin (MCPH1) in the nucleus and cytoplasm of mouse HSCs. In the nucleus, MCPH1 maintains genomic stability, whereas in the cytoplasm, it prevents necroptosis by binding with p-RIPK3. Aging triggers MCPH1 translocation from cytosol to nucleus, reducing its cytoplasmic retention and leading to the activation of necroptosis and deterioration of HSC function. Mechanistically, we found that KAT7-mediated lysine acetylation within the NLS motif of MCPH1 in response to DNA damage facilitates its nuclear translocation. Targeted mutation of these lysines inhibits MCPH1 translocation and, consequently, compromises necroptosis. The dysfunction of necroptosis signaling, in turn, improves the function of aged HSCs. In summary, our findings demonstrate that DNA damage-induced redistribution of MCPH1 promotes HSC aging and could have broader implications for aging and aging-related diseases.

Quantitative evaluation of the impact of relaxing eligibility criteria on the risk-benefit profile of drugs for lung cancer based on real-world data.

INTRODUCTION: Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. METHODS: To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross-dimensional real-world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit-risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. DISCUSSION: This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.

The effect analysis of shape design of different charging piles based on Human physiological characteristics using the MF-DFA.

With the rapid development of new energy vehicles, the users have an increasing demand for charging piles. It is generally believed that the charging pile is a kind of practical product, and it only needs to realize the charging function. However, as a product, the shape design of the charging pile will directly affect the user experience, thus affecting product sales. Therefore, in the face of increasingly fierce market competition, when designing the shape of charging piles, it is necessary to adopt the traditional evaluation method and human physiological cognitive characteristics to evaluate the shape of charging piles more objectively. From the user's point of view, using the electroencephalogram (EEG) of the user, with the help of the multifractal detrended fluctuation analysis (MF-DFA) method, this paper comprehensively analyzes the differences in emotional cognitive characteristics between two kinds of charging piles, namely, the charging pile with a curved appearance design and the charging pile with square appearance design. The results show that there are significant differences in human physiological cognitive characteristics between two kinds of charging piles with different shapes. And different shapes of charging piles have different physiological cognitive differences for users. When designing charging pile product shapes, human beings can objectively evaluate the product shape design according to the physiological cognition differences of users, so as to optimize the charging pile product shape design.

A real-world study on the changing characteristics of measles antibodies in premature infants in China.

The waning of maternal antibodies may cause infants to lose protection against measles before receiving measles-containing vaccine (MCV). The aim of this study is to investigate the changing characteristics and influencing factors of measles antibodies in preterm infants (PT), and to provide scientific basis for optimizing MCV vaccination strategy of the target population. Blood samples were collected from PT and full-term infants (FT) at the chronological age (CA) of 3, 6, and 12 months. Measles antibodies were quantitatively detected by enzyme-linked immunosorbent assay. Demographic and vaccination information were both collected. Kruskal-Wallis rank sum test was used to compare the measles antibodies among different gestation age (GA) groups, and multiple linear regression was performed to identify the correlative factors for the antibodies. Measles antibodies of PT decreased significantly with age increasing before MCV vaccination. The positive rates of antibodies of PT were 10.80% and 3.30% at the age of 3 and 6 months, respectively (p < .001). At 12 months, the measles antibodies and seropositive rate in the infants who received MCV vaccination increased sharply (p < .001). Regression analyzes showed that the younger the GA or the older the age, the lower the antibodies at 3 months(p < .001，p = .018); while the lower measles antibody levels at 3 months and older age predicted the lower antibodies at 6 months(p < .001, p = .029). PT were susceptible to measles due to the low level of maternally derived antibodies before MCV vaccination. More efforts should be considered to protect the vulnerable population during their early postnatal life.

The application of HER2-ADC in future: More than expression.

We analyzed the potential of HER2-targeted antibody-drug conjugates (ADCs) in treating NSCLC with activating HER2 mutations. We identified specific mutations, notably G776delinsVC, that are associated with higher therapeutic response rates, suggesting a refined approach for precision treatment. Further validation and exploration are crucial for potential breakthroughs in ADC therapy.

Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells.

Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation bias toward myeloid lineages. However, the molecular mechanism behind HSC aging remains largely unknown. In this study, we observed that RNA N1-methyladenosine-generating methyltransferase TRMT6-TRMT61A complex is increased in aged murine HSCs due to aging-declined CRL4DCAF1-mediated ubiquitination degradation signaling. Unexpectedly, no difference of tRNA N1-methyladenosine methylome is observed between young and aged hematopoietic stem and progenitor cells, suggesting a noncanonical role of the TRMT6-TRMT61A complex in the HSC aging process. Further investigation revealed that enforced TRMT6-TRMT61A impairs HSCs through 3'-tiRNA-Leu-CAG and subsequent RIPK1-RIPK3-MLKL-mediated necroptosis cascade. Deficiency of necroptosis ameliorates the self-renewal capacity of HSCs and counters the physiologically deleterious effect of enforced TRMT6-TRMT61A on HSCs. Together, our work uncovers a nonclassical role for the TRMT6-TRMT61A complex in HSC aging and highlights a therapeutic target.

Aging-disturbed FUS phase transition impairs hematopoietic stem cells by altering chromatin structure.

ABSTRACT: Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity. The molecular mechanisms behind this phenomenon are not fully understood. Here, we observed that the expression of FUS is increased in aged HSCs, and enforced FUS recapitulates the phenotype of aged HSCs through arginine-glycine-glycine-mediated aberrant FUS phase transition. By using Fus-gfp mice, we observed that FUShigh HSCs exhibit compromised FUS mobility and resemble aged HSCs both functionally and transcriptionally. The percentage of FUShigh HSCs is increased upon physiological aging and replication stress, and FUSlow HSCs of aged mice exhibit youthful function. Mechanistically, FUShigh HSCs exhibit a different global chromatin organization compared with FUSlow HSCs, which is observed in aged HSCs. Many topologically associating domains (TADs) are merged in aged HSCs because of the compromised binding of CCCTC-binding factor with chromatin, which is invoked by aberrant FUS condensates. It is notable that the transcriptional alteration between FUShigh and FUSlow HSCs originates from the merged TADs and is enriched in HSC aging-related genes. Collectively, this study reveals for the first time that aberrant FUS mobility promotes HSC aging by altering chromatin structure.

Corrigendum: Analysis of a super-transmission of SARS-CoV-2 omicron variant BA.5.2 in the outdoor night market.

[This corrects the article DOI: 10.3389/fpubh.2023.1153303.].

Knowledge and awareness of viral hepatitis and influencing factors among the general population aged 15-69 years in Zhejiang Province, China.

This study aimed to determine the level of viral hepatitis knowledge as well as the self-awareness of hepatitis B virus surface antigen (HBsAg) positive individuals, to provide data support for the next steps in viral hepatitis prevention and control. We conducted a cross-sectional survey to assess the knowledge of viral hepatitis among the general population aged 15-69 years in Zhejiang Province, China. A total of 3,626 individuals were surveyed with 10 questions. The knowledge level of the participants is reflected by the scores from the survey. Adequate knowledge was defined as a score of ≥ 6. The knowledge rate was defined as the ratio of the number of individuals with adequate knowledge to the total number of individuals. The knowledge rate of viral hepatitis among the general population aged 15-69 years in Zhejiang Province was 52.34% (mean score, 5.23). The majority of participants (52.51%) had adequate knowledge of viral hepatitis. Multiple logistic regression analysis showed that medical staff had the best knowledge of viral hepatitis, followed by individuals with university or higher education, those aged 40-49 years, and those with a history of hepatitis B vaccination. 34.16% of HBsAg positive participants were aware of their infection status before. The mean score of knowledge of viral hepatitis was significantly lower among HBsAg-positive than HBsAg-negative individuals. Knowledge of viral hepatitis in Zhejiang Province was still low, especially among HBsAg-positive individuals with no awareness of their infection status. More effort should be needed to improve public awareness of viral hepatitis.

Analysis of a super-transmission of SARS-CoV-2 omicron variant BA.5.2 in the outdoor night market.

Introduction: The COVID-19 pandemic continues to ravage the world, and mutations of the SARS-CoV-2 continues. The new strain has become more transmissible. The role of aerosol transmission in the pandemic deserves great attention. Methods: In this observational study, we collected data from market customers and stallholders who had been exposed to the virus in the Qingkou night market on July 31 and were subsequently infected. We analyzed the possible infection zones of secondary cases and aerosol suspension time in ambient air. We described and analyzed the characteristics of the secondary cases and the transmission routes for customers. Results: The point source outbreak of COVID-19 in Qingkou night market contained a cluster of 131 secondary cases. In a less-enclosed place like the Qingkou night market, aerosols with BA.5.2 strain released by patients could suspend in ambient air up to 1 h 39 min and still be contagious. Conclusion: Aerosols with viruses can spread over a relatively long distance and stay in ambient air for a long time in a less enclosed space, but shorter than that under experimental conditions. Therefore, the aerosol suspension time must be considered when identifying and tracing close contact in outbreak investigations.

Immuno-persistence of the different primary polio vaccine schedules and immunogenicity of the booster dose by sabin inactivated or bivalent oral poliovirus vaccine in children aged 4 years: an open-label, randomised, controlled phase 4 trial in China.

Background: Sabin inactivated and bivalent oral poliovirus vaccine (sIPV, bOPV) were commonly used in China since 2016. We conducted an open-label, randomised, controlled phase 4 trial to assess immune persistence following sequential immunisation with sIPV or bOPV, and immunogenicity and safety of a booster dose of poliovirus vaccine in children aged 4 years. Methods: Participants from a previous clinical trial with three different sequential schedules with sIPV (I) or bOPV (B) at ages 2, 3, and 4 months (Groups I-B-B, I-I-B, I-I-I) in 2017 were followed-up. The children were further divided into five subgroups after sIPV was given for Group I-B-B, and sIPV or bOPV randomly given for Group I-I-B and Group I-I-I (128 children in Groups I-B-B-I, 60 in Group I-I-B-B, 64 in Group I-I-B-I, 68 in Group I-I-I-B, 67 in Group I-I-I-I). Immune persistence and immunogenicity were assessed by measuring poliovirus type-specific antibodies, and safety were analysed in all children who received the booster dose. Findings: Between Dec 5, 2020 and Jun 30, 2021, we respectively enrolled 381 participants in the immune persistence analysis, and 352 participants in per protocol (PP) analysis of the immunogenicity of the booster immunisation. Seropositivity rates of antibodies against poliovirus types 1 and 3 were all >90% four years after primary immunisation, while for poliovirus type 2 were 46.83%, 75.41%, and 90.23% (χ2 = 60.948, P < 0.001) for Groups I-B-B, I-I-B, and I-I-I, respectively. After the booster dose, seropositivity rates were 100% for all three serotypes in Group I-B-B-I, I-I-B-I and I-I-I-I; In Group I-I-B-B and I-I-I-B, the seropositivity rates for types 1 and 3 were all 100%, for type 2 were 92.59% and 98.46%. The geometric mean titres (GMTs) against poliovirus 1 and 3 were all high in five groups (>1860.73), and the GMTs against type 2 were significantly lower in groups booster with bOPV: Group I-I-B-B (50.60) and Group I-I-I-B (247.84). There was no significant difference in seropositivity rates or GMTs for all three serotypes (P > 0.05) between Group I-I-B-I and I-I-I-I. No serious adverse events occurred during the study. Interpretation: Our findings suggest that at least two sIPV doses are needed in the current routine poliovirus immunisation schedule, and schedules containing 3 or 4 doses of sIPV provide better protection against poliovirus type 2 than the current sIPV-sIPV-bOPV-bOPV schedule in China. Funding: Medical and Health Science and Technology of Zhejiang Province (2021KY118). This trial was registered with ClinicalTrials.gov (NCT04576910).

Aging-induced pseudouridine synthase 10 impairs hematopoietic stem cells.

Aged hematopoietic stem cells (HSC) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage, however, the molecular mechanism behind it remains not fully understood. In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPC) and enforced protein of Ψ synthase 10 (PUS10) recapitulates the phenotype of aged HSC, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of transcribed RNA pseudouridylation profile between young and aged HSPC. No significant alteration of hematopoietic homeostasis and HSC function is observed in young Pus10-/- mice, while aged Pus10-/- mice exhibit mild alteration of hematopoietic homeostasis and HSC function. Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. Taken together, this study for the first time evaluated the role of PUS10 in HSC aging and function, and provided a novel insight into HSC rejuvenation and its clinical application.

Assessing COVID-19 Vaccine Booster Hesitancy Using the Modified 5C Scale in Zhejiang Province, China: A Cross-Sectional Study.

Following the rollout of a booster campaign to promote immunity against COVID-19 in China, this study aimed to assess booster hesitancy among adults who were fully vaccinated with primary doses across Zhejiang Province. Firstly, the modified 5C scale developed by a German research team was assessed for reliability and validity via a pre-survey in Zhejiang Province. Then, a 30-item questionnaire was established to conduct online and offline surveys during 10 November to 15 December 2021. Demographic characteristics and information on previous vaccination experience, vaccine type of primary doses, attitudes towards booster doses and awareness of SARS-CoV-2 infection were collected. Chi-square tests, pairwise comparison and multivariate logistic regression were performed in data analysis. In total, 4039 valid questionnaires were analyzed, with booster hesitancy of 14.81%. Dissatisfaction with previous vaccination experience of primary doses (ORs = 1.771~8.025), less confidence in COVID-19 vaccines (OR = 3.511, 95%CI: 2.874~4.310), younger age compared to the elderly aged 51-60 years old (2.382, 1.274~4.545), lower education level (ORs = 1.707~2.100), weaker awareness of social responsibility of prevention and control of COVID-19 (1.587, 1.353~1.859), inconvenience of booster vaccination (1.539, 1.302~1.821), complacency regarding vaccine efficacy as well as self-health status (1.224, 1.056~1.415) and excessive trade-offs before vaccination (1.184, 1.005~1.398) were positively associated with booster hesitancy. Therefore, intelligent means should be strengthened to optimize vaccination services. More influential experts and other significant figures should be supported to promote timely evidence-based information via various media platforms to reduce public hesitancy and increase booster uptake.

The infection rates of HBV and HCV decreased significantly in Zhejiang Province, China: A comparative study based on the data of two sero-epidemiological surveys in 1992 and 2020.

In 2020, China conducted a nationwide, sero-epidemiological, cross-sectional survey of viral hepatitis. The stratified multi-stage cluster random sampling method was used to select the permanent population aged 1-69 years, followed by questionnaire survey and sample collection and detection of the serological markers of hepatitis B (HBV) and hepatitis C viruses (HCV). A total of 4747 individuals aged 1-69 years were investigated in Zhejiang Province. The positive rates of hepatitis B surface antigen and anti-HCV were 4.3% and 0%, respectively. Compared to a similar sero-epidemiological survey in 1992, the 2020 survey showed that the HBV infection rate in Zhejiang Province decreased by 56.5%. In both surveys, HBV infection rate increased with age (in 1992, χ2  = 185.866, p = .000; in 2020, χ2  = 1383.836, p = .000). Compared with 1992, the positive anti-HCV rate in those aged 1-69 years in 2020 decreased by 100.0%. This result showed that the HBV vaccine and blood screening to prevent HBV and HCV infection significantly decreased the infection rate of HBV and HCV in the younger generation of Zhejiang province. However, the rate of HBV carriers aged 30-69 years was still high, which underscores the need to strengthen the management and treatment of chronic HBV infection. Hence, Zhejiang province can eliminate the public health threat of viral hepatitis.

Immunogenicity and safety of an inactivated enterovirus 71 vaccine coadministered with trivalent split-virion inactivated influenza vaccine: A phase 4, multicenter, randomized, controlled trial in China.

Background: Few data exist on the immunogenicity and safety of an inactivated enterovirus 71 vaccine (EV71 vaccine) coadministered with trivalent split-virion inactivated influenza vaccine (IIV3) in infants. Methods: This trial was a phase 4, randomized, controlled trial. Infants aged 6-11 months were eligible, with no history of hand, foot and mouth disease (HFMD) and no history of EV71 vaccine or any influenza vaccine. Eligible infants were randomly assigned to EV71+IIV3 group, EV71 group or IIV3 group. Blood samples were collected on day 0 and 56. Results: Between September 2019 and June 2020, 1151 infants met eligibility criteria and 1134 infants were enrolled. 1045 infants were included in the per-protocol population, including 347 in the EV71+IIV3 group, 343 in the EV71 group, and 355 in the IIV3 group. The seroconversion rate (98.56% vs 98.54%; seroconversion rates difference of 0.02% [95% CI: 0.70-0.98]) and GMT (419.05 vs 503.72; GMT ratio of 0.83 [95% CI 0.70 - 0.98]) of EV71 neutralizing antibodies in the EV71+IIV3 group was not inferior to those in the EV71 group. The non-inferiority results for influenza virus antibodies (A/H1N1, A/H3N2 and B) showed that the seroconversion rates and GMTs of the EV71+IIV3 group were non-inferiority to those of the IIV3 group. Systemic and local adverse event rates were similar between groups. None of serious adverse events (SAEs) were related to vaccination. Conclusions: Coadministration of the EV71 vaccine with IIV3 was safe and did not interfere with immunogenicity. These findings support a viable immunization strategy for infants with the EV71 vaccine coadministered with IIV3 in China. This trial is registered with ClinicalTrials.gov, number NCT04091880.

The decline in immunity and circulation of pertussis among Chinese population during the COVID-19 pandemic: A cross-sectional sero-epidemiological study.

BACKGROUND: In recent years, the resurgence of pertussis has posed a public health challenge in many countries. This study aimed to evaluate the immunity levels against pertussis among populations of different ages in China. METHODS: We conducted a cross-sectional serological survey in Zhejiang Province, China in 2020. Serum IgG antibodies against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA), and pertactin (anti-PRN) were quantitatively measured. The geometric mean concentration (GMC) of three antibodies was calculated. An anti-PT level < 5 IU/mL was considered undetectable, ≥20 IU/mL as seropositive and ≥80 IU/mL as an indicator of recent infection. Mathematical models were fitted for anti-PT concentrations over time in children after four doses of the pertussis vaccination. RESULTS: A total of 4459 participants aged 0-59 years were included in the analyses. The overall positivity rate of anti-PT was 29.80% with the highest (81.44%) rate in the 1-2 years old and the lowest (4.72%) in 10-14 years old. The GMCs of anti-PT, anti-FHA and anti-PRN for the whole participants were 9.67 (95%CI: 9.25-10.10),18.93 (18.24-19.67), and 8.99 (8.61-9.38) IU/mL, respectively. Over 50% of subjects aged ≥ 7 years had undetectable anti-PT IgG antibodies (<5IU/mL). The proportions of the populations with anti-PT IgG ≥ 80 IU/mL were approximately 0.9%, 0.3% and 1.1% among the 10-14, 15-29, and 40-59 years old groups, respectively. The power regression equation of the attenuation model after last dose of pertussis vaccine was y = 41.088x-1.238 (R2 = 0.935, p < 0.001). The fitted anti-PT concentrations was only 5.60 IU/mL at 5 years following the last vaccination dose. CONCLUSION: The prevalence of pertussis decreased during the study period in the COVID-19 pandemic; however, there was still a certain proportion of adolescents and adults with evidence of recent infection. The decline in antibody levels after pertussis vaccination was observed, and booster doses are in urgent need in China.

Burden of whooping cough in China (PertussisChina): study protocol of a prospective, population-based case-control study.

INTRODUCTION: Pertussis is one of the top 10 diseases of children under 10 years of age, and the few vaccine-preventable diseases who is on a rise in China in recent years; however, the true burden of pertussis, including age-stratified incidence and risk factors of severe sequelae, are under-recognised. We aim to estimate the health burden of laboratory-confirmed pertussis by age groups, considering the setting of illness onset (ie, in community, outpatient and inpatient), in a Chinese population (~2.23 million in total) at two sites. METHODS AND ANALYSIS: This paper describes the study design of a 1-year, prospective, age-stratified and population-based case-control study, including site selection, study population, case registry, ascertainment and enrolment, control recruitment, follow-up of case, microbiological methods, data collection, quality control activities and statistical methods used to generate incidence estimates. During June 2021 through May 2022, registry of suspected pertussis cases (namely chronic/persistent cough) will be conducted in several participating hospitals (SHs) at the two sites, which are selected based on Healthcare Utilisation and Attitudes Surveys (HUAS) carried out before study initiation. A case-control study will be conducted in the SHs and we aim to enrol a total of 1000 suspected pertussis cases (ie, all hospital admissions and the first 1-3 outpatient visits each week each hospital) and 2000 frequency matched healthy controls in community. Our primary study outcome, the laboratory-confirmed Bordetella pertussis infection, will be determined by a comprehensive laboratory methods and procedures (ie, culture, PCR and serological tests) in both cases and controls at enrolment and during 60-day's follow-up visits. Finally, data from HUAS (ie, population size), case registry (ie, the total number of suspected pertussis cases) and case-control study (ie, the prevalence or population attributable fraction of Bordetella pertussis) will be combined to calculate incidence and its 95% CI through bootstrap method. Epidemiological analyses will be conducted to determine the risk factors associated with severe sequelae of pertussis. ETHICS AND DISSEMINATION: This study has been approved by Chinese Centre for Disease Control and Prevention's Institutional Review Board (no. ICDC-202110). Results will be disseminated via academic presentations and publication in peer-reviewed journals, and will provide valuable scientific data and some new insights into the incidence, aetiology and risk factors for severe sequelae of pertussis to academic societies and the public health authorities who is currently struggling and fighting against this burdensome disease worldwide.

Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis.

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

Post-vaccination serologic testing of infants born to hepatitis B surface antigen-positive mothers is more cost-effective in Zhejiang Province, China: A Markov chain analysis.

To evaluate the cost-effectiveness of the post-vaccination serologic testing (PVST) plus active-passive immunoprophylaxis of infants born to hepatitis B surface antigen (HBsAg)-positive mothers, a Markov model was constructed by R 4.0.1 to compare the current strategy (three-dose HepB plus HBIG) and the PVST strategy (post-vaccination serologic testing plus the current strategy) for infants of HBsAg-positive mothers. Costs and utility scores were assessed from a field survey. Other model inputs were extracted from published literature and unpublished data from the Zhejiang provincial center for disease control and prevention (Zhejiang CDC). We calculated the incremental cost-effectiveness ratio (ICER) as the main result within 1-year cycle length with a 81 horizon among 50,000 infants and performed one-way sensitivity analysis and probabilistic sensitivity analysis to explore the reliability of outcome. The ICER was -4130.18 yuan/quality-adjusted life year (QALY) for the PVST strategy compared with the current strategy from the societal perspective. It was estimated that the PVST strategy would save about 3,809,546 yuan and prevent loss of 922.37 QALYs within 81 cycles among 50,000 infants. ICER was most sensitive to the discount rate, and the cost-effectiveness acceptability curves showed that the PVST strategy reached a probability of being 100% cost-effective below willing to pay (107,624 yuan). In conclusion, the PVST strategy had increased the utility and reduced cost among infants born to HBsAg-positive mothers. The PVST strategy is a more cost-effective choice for infants born to HBsAg-positive mothers than the current strategy, and further promotion of the PVST project is recommended.

Spatio-temporal distribution characteristics of mumps in Zhejiang Province from 2008 to 2019 / 预防医学

Objective @#To identify spatio-temporal distribution patterns of mumps in Zhejiang Province from 2008 to 2019, so as to provide insights into precise control of mumps.@*Methods @#The epidemiological data pertaining to mumps in Zhejiang Province from 2008 to 2019 were collected from the China Information System for Disease Control and Prevention. The time- and region-specific incidence of mumps was descriptively analyzed, and the spatio-temporal clustering characteristics of mumps incidence were identified using global and local spatial autocorrelation analyses and spatio-temporal scan analysis.@*Results @#A total of 167 196 cases of mumps were reported in Zhejiang Province from 2008 to 2019, and the incidence of mumps reduced from 56.08/105 in 2008 to 11.35/105 in 2019, with a reduction of 79.76%. There was no remarkable mumps seasonality since 2017; however, spatial autocorrelation was seen in mumps incidence in 2008, 2011 and 2012, respectively ( Moran's I coefficient=0.16, 0.18, 0.16; all P<0.05 ). Spatio-temporal scan analysis identified five spatio-temporal clusters of mumps incidence in 2008, 2011 and 2012, and the most likely spatio-temporal cluster was mainly concentrated in Cangnan County of Wenzhou City, covering 17 counties clustered in the time frame from 15 January 2008 to 28 February 2009, while the other four clusters were concentrated in Pinghu City of Jiaxing City, Kaihua County of Quzhou City, Fuyang District of Hangzhou City and Zhuji City of Shaoxing City, clustered in the time frame from 15 January 2008 to 30 June 2012. @*Conclusion @#The incidence of mumps appeared a tendency towards a reduction in Zhejiang Province from 2008 to 2019, and rebounded in some regions. No remarkable mumps seasonality was seen since 2017. The spatio-temporal clusters of mumps incidence were concentrated in Wenzhou and Jiaxing cities of Zhejiang Province in 2008, 2011 and 2012; however, no spatial cluster was identified since 2012.