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BackgroundIn recent years, radiation diagnosis and treatment technology has been increasingly applied and popularized in the medical field, and the status of radiation health protection has attracted widespread attention. ObjectiveTo understand the knowledge, attitude, and behavior of radiological health protection in radiation workers in Jiading District of Shanghai. MethodsConvenience sampling method was used to select 441 radiation workers from 33 medical institutions in Jiading District, Shanghai to conduct a questionnaire survey from May to August 2023. Basic information and radiation protection associated knowledge, attitude, and behavior were collected from the study participants, and the scores of knowledge, attitude, and behavior were calculated. Factors affecting the behavior were evaluated by multiple linear regression. ResultsA total of 441 subjects were included in this study, with an age range of 22-71 years, 53.06% male and 46.94% female. In terms of knowledge, the correct response rate of the study subjects to the seven questions on the basics of radiation protection ranged from 44.22%-96.60%, with the lowest rate of 44.22% for the question on "radiation stochastic effect diseases". The subjects acquired knowledge about radiation hygiene mainly through vocational training (98.41%), and wanted to acquire knowledge mainly about the basics of nuclear and radiation (76.42%). In terms of attitude, the recognition level (strongly agree/agree) of the study subjects on the six attitude questions ranged from 73.47% to 96.37%, in which only 56.92% of the radiological staff at tertiary hospitals believed that the radiation dose they were exposed to at work would be hazardous to their health, and 73.85% believed that it was necessary to participate in training on knowledge of radiological protection, both lower than those in other levels of hospitals. In terms of behavior, the implementation rate (always/often) of the five behavioral questions by the study participants ranged from 75.28% to 91.84%, and there was a statistically significant difference in the total behavioral scores of the study participants by levels of hospitals (P=0.015). The results of multiple linear regression showed that gender, age, and radiation work permit associated with the behavioral scores of the study subjects. ConclusionIn Jiading District, Shanghai, the coginitive rate of radiation workers' basic knowledge of theoretical protection still needs to be improved, and occupational training should be carried out in a targeted manner; the attitude of radiation workers varies by levels of hospitals, and the publicity and education of workers at tertiary hospitals in particular should be strengthened; and the supervision and management of male, senior, and non-certified radiation workers in hospitals of different levels should be enhanced.

Background: Shanghai experienced a significant surge in Omicron BA.2 infections from March to June 2022. In addition to the standard interventions in place at that time, additional interventions were implemented in response to the outbreak. However, the impact of these interventions on BA.2 transmission remains unclear. Methods: We systematically collected data on the daily number of newly reported infections during this wave and utilized a Bayesian approach to estimate the daily effective reproduction number. Data on public health responses were retrieved from the Oxford COVID-19 Government Response Tracker and served as a proxy for the interventions implemented during this outbreak. Using a log-linear regression model, we assessed the impact of these interventions on the reproduction number. Furthermore, we developed a mathematical model of BA.2 transmission. By combining the estimated effect of the interventions from the regression model and the transmission model, we estimated the number of infections and deaths averted by the implemented interventions. Results: We found a negative association (−0.0069, 95% CI: 0.0096 to −0.0045) between the level of interventions and the number of infections. If interventions did not ramp up during the outbreak, we estimated that the number of infections and deaths would have increased by 22.6% (95% CI: 22.4–22.8%), leading to a total of 768,576 (95% CI: 768,021-769,107) infections and 722 (95% CI: 722–723) deaths. If no interventions were deployed during the outbreak, we estimated that the number of infections and deaths would have increased by 46.0% (95% CI: 45.8–46.2%), leading to a total of 915,099 (95% CI: 914,639-915,518) infections and 860 (95% CI: 860–861) deaths. Conclusion: Our findings suggest that the interventions adopted during the Omicron BA.2 outbreak in spring 2022 in Shanghai were effective in reducing SARS-CoV-2 transmission and disease burden. Our findings emphasize the importance of non-pharmacological interventions in controlling quick surges of cases during epidemic outbreaks.

Background: China has experienced a COVID-19 wave caused by Omicron XBB variant starting in April 2023. Our aim is to conduct a retrospective analysis exploring the dynamics of the outbreak under counterfactual scenarios that combine the use of vaccines, antiviral drugs, and nonpharmaceutical interventions. Methods: We developed a mathematical model of XBB transmission in China, which has been calibrated using SARS-CoV-2 positive rates per week. Intrinsic age-specific infection-hospitalization risk, infection-ICU risk, and infection-fatality risk were used to estimate disease burdens, characterized as number of hospital admissions, ICU admissions, and deaths. Results: We estimated that in absence of behavioral change, the XBB outbreak in spring 2023 would have resulted in 0.86 billion infections (∼61% of the total population). Our counterfactual analysis shows that the synergetic effect of vaccination (70% vaccination coverage), antiviral treatment (20% receiving antiviral treatment), and moderate nonpharmaceutical interventions (20% isolation and L1 PHSMs) could reduce the number of deaths to levels close to seasonal influenza (1.17 vs. 0.65 per 10,000 individuals and 5.85 vs. 3.85 per 10,000 individuals aged 60+, respectively). The maximum peak prevalence of hospital and ICU admissions are estimated to be lower than the corresponding capacities (8.6 vs. 10.4 per 10,000 individuals and 1.2 vs. 2.1 per 10,000 individuals, respectively). Conclusion: Our findings suggest that the capacity of the Chinese healthcare system was adequate to face the Omicron XBB wave in spring 2023 but, at the same time, supports the importance of administering highly effective vaccine with long-lasting immune response, and the use of antiviral treatments.

Abstract Background The 2022–2023 mpox (monkeypox) outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM). In this study, we aimed to evaluate mpox’s importation risk, border screening effectiveness and the risk of local outbreak in Chinese mainland. Methods We estimated the risk of mpox importation in Chinese mainland from April 14 to September 11, 2022 using the number of reported mpox cases during this multi-country outbreak from Global.health and the international air-travel data from Official Aviation Guide. We constructed a probabilistic model to simulate the effectiveness of a border screening scenario during the mpox outbreak and a hypothetical scenario with less stringent quarantine requirement. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. Results We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Under the quarantine policy, 15–19% of imported infections would remain undetected. Once a case of mpox is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to > 95% with over six cases. Conclusions Our study demonstrates that the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic reduced mpox importations prominently. However, the risk could be substantially higher with the recovery of air-travel volume to pre-pandemic level. Mpox could emerge as a public health threat for Chinese mainland given its large MSM community. Graphical Abstract

Abstract Background After the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern. Methods We conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2. Results Our study included 280 records obtained from 147 household studies, contact tracing studies, or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods, although we did not find statistically significant differences between the Omicron subvariants. We found that Omicron BA.1 had the shortest pooled estimates for the incubation period (3.49 days, 95% CI: 3.13–4.86 days), Omicron BA.5 for the serial interval (2.37 days, 95% CI: 1.71–3.04 days), and Omicron BA.1 for the realized generation time (2.99 days, 95% CI: 2.48–3.49 days). Only one estimate for the intrinsic generation time was available for Omicron subvariants: 6.84 days (95% CrI: 5.72–8.60 days) for Omicron BA.1. The ancestral lineage had the highest pooled estimates for each investigated key time-to-event period. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. When pooling the estimates across different virus lineages, we found considerable heterogeneities (I 2 > 80%; I 2 refers to the percentage of total variation across studies that is due to heterogeneity rather than chance), possibly resulting from heterogeneities between the different study populations (e.g., deployed interventions, social behavior, demographic characteristics). Conclusions Our study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves.

Abstract Organic electrocatalytic conversion is an essential pathway for the green conversion of low-cost organic compounds to high-value chemicals, which urgently demands the development of efficient electrocatalysts. Here, we report a Cu single-atom dispersed Rh metallene arrays on Cu foam for cathodic nitrobenzene electroreduction reaction and anodic methanol oxidation reaction. In the coupled electrocatalytic system, the Cusingle-atom-Rh metallene arrays on Cu foam requires only the low voltages of 1.18 V to reach current densities of 100 mA cm−2 for generating aniline and formate, with up to ~100% of nitrobenzene conversion/ aniline selectivity and over ~90% of formate Faraday efficiency, achieving synthesis of high-value chemicals. Density functional theory calculations reveal the electron effect between Cu single-atom and Rh host and catalytic reaction mechanism. The synergistic catalytic effect and H*-spillover effect can improve catalytic reaction process and reduce energy barrier for reaction process, thus enhancing electrocatalytic reaction activity and target product selectivity.

Abstract Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.

Abstract Purpose Small cell lung cancer (SCLC) is an aggressive and rapidly progressive malignant tumor characterized by a poor prognosis. Chemotherapy remains the primary treatment in clinical practice; however, reliable biomarkers for predicting chemotherapy outcomes are scarce. Methods In this study, 78 SCLC patients were stratified into “good” or “poor” prognosis cohorts based on their overall survival (OS) following surgery and chemotherapeutic treatment. Next-generation sequencing was employed to analyze the mutation status of 315 tumorigenesis-associated genes in tumor tissues obtained from the patients. The random forest (RF) method, validated by the support vector machine (SVM), was utilized to identify single nucleotide mutations (SNVs) with predictive power. To verify the prognosis effect of SNVs, samples from the cbioportal database were utilized. Results The SVM and RF methods confirmed that 20 genes positively contributed to prognosis prediction, displaying an area under the validation curve with a value of 0.89. In the corresponding OS analysis, all patients with SDH, STAT3 and PDCD1LG2 mutations were in the poor prognosis cohort (15/15, 100%). Analysis of public databases further confirms that SDH mutations are significantly associated with worse OS. Conclusion Our results provide a potential stratification of chemotherapy prognosis in SCLC patients, and have certain guiding significance for subsequent precise targeted therapy.

ABSTRACTFollowing the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9–45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9–45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006.

ABSTRACTOmicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.

Abstract Characterizing the long-term kinetics of maternally derived and vaccine-induced measles immunity is critical for informing measles immunization strategies moving forward. Based on two prospective cohorts of children in China, we estimate that maternally derived immunity against measles persists for 2.4 months. Following two-dose series of measles-containing vaccine (MCV) at 8 and 18 months of age, the immune protection against measles is not lifelong, and antibody concentrations are extrapolated to fall below the protective threshold of 200 mIU/ml at 14.3 years. A catch-up MCV dose in addition to the routine doses between 8 months and 5 years reduce the cumulative incidence of seroreversion by 79.3–88.7% by the age of 6 years. Our findings also support a good immune response after the first MCV vaccination at 8 months. These findings, coupled with the effectiveness of a catch-up dose in addition to the routine doses, could be instrumental to relevant stakeholders when planning routine immunization schedules and supplemental immunization activities.

Objectives: To quantify the seasonal and antigenic characteristics of influenza to help understand influenza activity and inform vaccine recommendations. Methods: We employed a generalized linear model with harmonic terms to quantify the seasonal pattern of influenza in China from 2005-2017, including amplitude (circulatory intensity), semiannual periodicity (given two peaks a year), annual peak time, and epidemic duration. The antigenic differences were distinguished as antigenic similarity between 2009 and 2020. We categorized regions above 33° N, between 27° N and 33° N, and below 27° N as the north, central, and south regions, respectively. Results: We estimated that the amplitude in the north region (median: 0.019, 95% CI: 0.018-0.021) was significantly higher than that in the central region (median: 0.011, 95% CI: 0.01-0.012, P

Summary: Background: Heterologous vaccine schedules have been recommended to provide superior immunity and protection against emergent SARS-CoV-2 variants of concern. We aimed to evaluate the safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine RQ3013 compared with adenoviral vectored vaccine Ad5-nCoV and protein subunit vaccine ZF2001 as the fourth dose in adults primed with three doses of inactivated vaccines in China. Methods: We conducted a double-blinded, randomised, controlled, phase 3b trial among healthy Chinese adults at Lancang County, Yunnan, China. Adults who had received three doses of inactivated COVID-19 vaccines at least 6 months prior were randomly allocated (3:1:1) to receive heterologous boosters with RQ3013, Ad5-nCoV, or ZF2001. We assessed safety within 28 days post boost and the serum geometric mean titres (GMTs) of neutralising antibodies (NAbs) against the live SARS-CoV-2 omicron variant BA.5 on day 14 post-boost. We used Poisson regression to assess the vaccine efficacy against the first episode of virologically confirmed symptomatic COVID-19 occurring at least 7 days post boost. Subgroup analyses categorized by age and sex were also performed for safety and immunogenicity outcomes. This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2200065281) and is now complete. Findings: Between December 12 and December 18, 2022, a total of 1382 adults were screened, and 1250 were enrolled and randomly assigned to receive one dose of RQ3013 (n = 750), Ad5-nCoV (n = 250), or ZF2001 (n = 250). Although solicited adverse reactions within 28 days post boost were more frequent in the RQ3013 group (175 [23.3%]) compared to the control groups (24 [9.6%] in both the Ad5-nCOV and ZF2001 groups, P 0.05). On day 14 post-boost, RQ3013 (GMT 69.14, 95% CI 47.90–99.81) elicited 4.8-fold and 5.6-fold higher concentrations of NAbs against BA.5 than did Ad5-nCoV (14.37, 7.78–26.56) and ZF2001 (12.21, 5.13–29.06), respectively. On day 28 post-boost, RQ3013 demonstrated a relative efficacy of 62.2% (95% CI 13.7–83.1, P = 0.02) compared to Ad5-nCoV, and of 69.0% (33.5–85.7, P = 0.002) compared to ZF2001. Interpretation: The administrations of all the three heterologous boosters were well tolerated. The heterologous prime-boost regimen with RQ3013 elicited superior immune responses and demonstrated better protection against symptomatic SARS-CoV-2 infections compared with Ad5-nCoV or ZF2001, supporting the use of RQ3013 as a booster vaccination in adults. Funding: Yunnan Province Science and Technology Department (grant no.202302AA310047).

A novel coronavirus emerged in late 2019, named as the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). This study was originally conducted in January 2020 to estimate the potential risk and geographic range of COVID-19 spread at the early stage of the transmission. A series of connectivity and risk analyses based on domestic and international travel networks were conducted using historical aggregated mobile phone data and air passenger itinerary data. We found that the cordon sanitaire of the primary city was likely to have occurred during the latter stages of peak population numbers leaving the city, with travellers departing into neighbouring cities and other megacities in China. We estimated that there were 59,912 international air passengers, of which 834 (95% uncertainty interval: 478–1,349) had COVID-19 infection, with a strong correlation seen between the predicted risks of importation and the number of imported cases found. Given the limited understanding of emerging infectious diseases in the very early stages of outbreaks, our approaches and findings in assessing travel patterns and risk of transmission can help guide public health preparedness and intervention design for new COVID-19 waves caused by variants of concern and future pandemics to effectively limit transmission beyond its initial extent.

Abstract Background In segmentectomy, in addition to the anatomy of the segmental hilum, the identification and separation of the intersegmental plane is also an important step of the operation. Because of its simplicity and high efficiency, most thoracic surgeons choose the staplers. But the energy devices also have its unique advantages in the separation of the intersegmental plane. This study compared the clinical efficacy of staplers and energy devices in the separation of the intersegmental planes during the uniport thoracoscopic segmentectomy through the clinical data. Methods Clinical data of 89 patients undergoing uniport VATS lung segmentectomy from January 2019 to October 2020 at the First Affiliated Hospital of Soochow University were analyzed retrospectively. According to the different treatment methods of intersegmental plane, the patients were divided into two groups, 55 in the stapler group and 34 in the energy device group. The clinical data of the two groups were compared and analyzed statistically. And the univariate and multivariate logistic regression were also used to explore the influencing factors of postoperative complications. Results Lung segmentectomy was successfully operated in both groups. There were statistically significant differences in operative duration, number of staplers used, surgical expenses and postoperative complications (P 0.05). Smoking history (OR 5.08, 95% CI 1.05–24.56, P = 0.043) and intersegmental plane treatment (OR 3.18, 95% CI 1.11–9.14, P = 0.031) were risk factors for postoperative complications. Patients of the energy device group had a higher incidence of postoperative complications. Conclusions In uniport thoracoscopic segmentectomy, the use of energy devices to treat the intersegmental plane will result in longer operative duration and higher postoperative complication rate, but it does not affect postoperative recovery and can help reduce surgical expenses. Both methods are safe and reliable. Clinically, the two methods can be reasonably selected according to the specific situation.

An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February 26 to June 30, 2022. We use official reported data retrieved from Shanghai municipal Health Commissions to estimate the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and RT-PCR sensitivity, we provide estimates of clinical severity, including the infection fatality ratio, symptomatic case fatality ratio, and risk of developing severe/critical disease upon infection. The overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age, noted in individuals aged 80 years or older. The overall fatality ratio and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.09-0.10%) and 0.27% (95% CI: 0.24-0.29%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death.

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3–11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 89% across the eligible age groups. Extending the vaccination roll-out to include children aged 3–11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

Hand, foot and mouth disease, caused by enterovirus A71 (EV-A71) infection, is common in children in China. Here, the authors estimate EV-A71 incidence and seroprevalence using data from two longitudinal cohorts and find that, despite high infection rates, a large proportion of children under 6 are susceptible.

Abstract Background The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic. Methods We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China’s current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. Results We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China’s pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. Conclusions As China’s current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

Abstract Background A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children. Methods Two population-based longitudinal cohorts in southern China were studied during 2013–2018. Participants were enrolled in autumn 2013, including 2475 children aged 1–9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated. Results The average maternal antibody transfer ratio was 0.88 (95% CI 0.80–0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9–2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64. Conclusions Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0–5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.

Enterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell RNA and B cell receptor sequencing of peripheral blood mononuclear cells. From 145 plasmablasts, we identified two IgG1 monoclonal antibodies (mAbs) and six IgM mAbs that neutralized EV-A71. Four of the IgM mAbs harbor germline variable sequences and neutralize EV-A71 potently. Two genetically similar IgM antibodies from two patients have recurrent heavy chain variable domain gene usage and similar complementarity-determining region 3 sequences. We mapped the residues of EV-A71 critical for neutralization through selection of virus variants resistant to antibody neutralization in the presence of neutralizing mAbs. The residues critical for neutralization are conserved among EV-A71 genotypes. Epitopes for the two genetically similar antibodies overlap with the SCARB2 binding site of EV-A71. We used escape variants to measure the epitope-specific antibody response in acute phase serum samples from EV-A71 infected HFMD patients. We found that these epitopes are immunogenic and contributed to the neutralizing antibody response against the virus. Our findings advance understanding of antibody response to EV-A71 infection in young children and have translational potential: the IgM mAbs could potentially be used for prevention or treatment of EV-A71 infections.

Shanghai and Hong Kong, China, experienced an outbreak of COVID-19 in early 2022. Both cities had similar dynamic prevention policies and population-level immunity, but showed differences in the numbers of cases and deaths. We collected data from official websites to estimate and compare the infection rates, mortality rates, and infection fatality ratios (IFRs) between cities. We further performed univariable analysis and used two tree models to explore the factors affecting the differences. The infection rate in Hong Kong, China, was 42.45 (95% CI: 42.41–42.48) per 100 individuals (15.49 times higher than that in Shanghai). The mortality rate was 124.90 (95% CI: 122.33–127.46) per 100,000 individuals (51.61 times higher than that in Shanghai). The adjusted IFR was 0.29% (95% CI: 0.29–0.30%) (3.30 times higher than that in Shanghai). The infection rate was negatively correlated with the stringency of nonpharmaceutical interventions. The mortality rate and IFR negatively correlated with the vaccination rate. However, positive correlations were observed between the median age and both mortality and IFR, as well as between the proportion of people ≥65 and IFR. Overall, a lack of medical resources, lower vaccination rates, and higher median age were associated with a higher infection rate, mortality rate, and IFR in Hong Kong.

Following a booster dose of CoronaVac in two single-centre phase 2 clinical trials, the authors show that neutralising antibody titres decline approximately 4-fold and 2.5-fold from day 28 to day 180 in adults aged 18-59 years and in adults aged 60 years and older, respectively.

The lysosome is an important target for realizing antitumor therapy. Lysosomal cell death exerts significant therapeutic effects on apoptosis and drug-resistance. The development of lysosome-targeting nanoparticles to obtain efficient cancer treatment is challenging. In this article, nanoparticles composed of DSPE@M-SiPc and possessing bright two-photon fluorescence, lysosome targeting ability, and photodynamic therapy multifunctionalities are prepared by encapsulating morpholinyl-substituted silicon phthalocyanine (M-SiPc) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE). Two photon fluorescence bioimaging showed that M-SiPc and DSPE@M-SiPc mainly locate in lysosomes after cellular internalization. Upon irradiation, DSPE@M-SiPc effectively generates reactive oxygen species and damages the function of lysosome, subsequently leading to lysosomal cell death. DSPE@M-SiPc is a promising photosensitizer for cancer treatment.

Abstract Background Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. Methods We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries’ target populations according to their national immunization program policies. Results Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R 2 = 0.59), socio-demographic index (R 2 = 0.52), and gross domestic product per capita (R 2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs—3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. Conclusions There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Abstract Background China experiences large variations in influenza seasonal activity. We aim to update and improve the current understanding of regional-based within-year variations of influenza activity across mainland China to provide evidence for the planning and optimisation of healthcare strategies. Methods We conducted a systematic review and spatio-temporal meta-analysis to assess regional-based within-year variations of ILI outpatient consultation rates, influenza test positivity rates amongst both ILI outpatients and SARI inpatients, and influenza-associated excess mortality rates. We searched English and Chinese databases for articles reporting time-series data on the four influenza-related outcomes at the sub-national and sub-annual level. After synthesising the data, we reported on the mean monthly rate, epidemic onset, duration, peak and intensity. Results We included 247 (7.7%) eligible studies in the analysis. We found within-year influenza patterns to vary across mainland China in relation to latitude and geographic location. High-latitude provinces were characterised by having short and intense annual winter epidemics, whilst most mid-latitude and low-latitude provinces experience semi-annual epidemics or year-round activity. Subtype activity varied across the country, with A/H1N1pdm09 and influenza B occurring predominantly in the winter, whereas A/H3N2 activity exhibited a latitudinal divide with high-latitude regions experiencing a winter peak, whilst mid and low-latitude regions experienced a summer epidemic. Epidemic onsets and peaks also varied, occurring first in the north and later in the southeast. We found positive associations between all influenza health outcomes. In addition, seasonal patterns at the prefecture and county-level broadly resembled their wider province. Conclusions This is the first systematic review to simultaneously examine the seasonal variation of multiple influenza-related health outcomes at multiple spatial scales across mainland China. The seasonality information provided here has important implications for the planning and optimisation of immunisation programmes and healthcare provision, supporting the need for regional-based approaches to address variations in local epidemiology.

Reactive school class closures have been widely implemented to mitigate COVID-19 outbreaks. Here, the authors show that, compared to symptom-prompted PCR testing, screening for cases in schools with antigen tests leads to greater reductions in infection rates in both students and the wider community.

Abstract Background Evidence on vaccine-specific protection over time, in particular against the Delta variant, and protection afforded by a homologous third dose is urgently needed. Methods We used a previously published model and neutralization data for five vaccines—mRNA-1273, BNT162b2, NVX-CoV2373, V01, and CoronaVac— to evaluate long-term neutralizing antibody dynamics and predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity. Results We found that homologous third-dose vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacy of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95% CI: 51.4–67.3%) and 78.4% (95% CI: 72.2–83.5%), respectively, 14–30 days after the second dose, and that efficacy decreases to 36.0% (95% CI: 24.1–58.0%) and 38.5% (95% CI: 28.7–49.1%) 6–8 months later. Fourteen to 30 days after administration of homologous third doses, efficacy against the Delta variant would be 97.0% (95% CI: 96.4–98.5%) and 97.2% (95.7–98.1%). All five vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and homologous third dose vaccination. Conclusions Timely administration of third doses of SARS-CoV-2-prototype-based vaccines can provide protection against the Delta variant, with better performance from mRNA vaccines than from protein and inactivated vaccines. Irrespective of vaccine technology, a homologous third dose for all types of vaccines included in the study will effectively prevent symptomatic and severe COVID-19 caused by the Delta variant. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody levels or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants, are needed to inform COVID-19 pandemic responses.

Abstract Background To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. Methods We developed a compartmental model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. Two vaccination programs were tested and model-based estimates of the immunity level in the population were provided. Results We found that it is unlikely to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021 and the lack of prior natural immunity. We estimated that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 50–62% in case of an all-or-nothing vaccine model and an epidemic starts to unfold on December 1, 2021. Conclusions Efforts should be taken to increase population’s confidence and willingness to be vaccinated and to develop highly efficacious vaccines for a wide age range.

InteractionDespite numerous recent insights into neighbor detection and belowground plant communication mediated by root exudates, less is known about the specificity and nature of substances within root exudates and the mechanism by which they may act belowground in root-root interactions.MethodsHere, we used a coculture experiment to study the root length density (RLD) of tomato (Solanum lycopersicum L.) grown with potato onion (Allium cepa var. aggregatum G. Don) cultivars with growth-promoting (S-potato onion) or no growth-promoting (N-potato onion) effects.Results and DiscussionTomato plants grown with growth-promoting potato onion or its root exudates increased root distribution and length density oppositely and grew their roots away as compared to when grown with potato onion of no growth-promoting potential, its root exudates, and control (tomato monoculture/distilled water treatment). Root exudates profiling of two potato onion cultivars by UPLC-Q-TOF/MS showed that L-phenylalanine was only found in root exudates of S-potato onion. The role of L-phenylalanine was further confirmed in a box experiment in which it altered tomato root distribution and forced the roots grow away. In vitro trial revealed that tomato seedlings root exposed to L-phenylalanine changed the auxin distribution, decreased the concentration of amyloplasts in columella cells of roots, and changed the root deviation angle to grow away from the addition side. These results suggest that L-phenylalanine in S-potato onion root exudates may act as an “active compound” and trigger physio-morphological changes in neighboring tomato roots.

Background: We aimed to compare the efficacy and safety of bivalirudin versus heparin as the anticoagulant in patients undergoing extracorporeal membrane oxygenation (ECMO). Methods: We conducted a search in PubMed, Embase and the Cochrane Library for all the studies in which bivalirudin was compared to heparin as the anticoagulant for ECMO. Efficacy outcomes were defined as the time to reach therapeutic levels, time within therapeutic range (TTR), thrombotic events, circuit thrombosis, circuit exchanges. Safety outcomes were reported as heparin-induced thrombocytopenia (HIT), major bleeding events, minor bleeding events. Other outcomes included hospital length of stay (LOS), ICU LOS, mortality, 30-day mortality and in-hospital mortality. Results: Ten studies with 1091 patients were included for meta-analysis. A significant reduction in thrombotic events [OR 0.51, 95%CI 0.36,0.73, p = 0.0002, I2 = 0%], major bleeding events [OR 0.31, 95%CI 0.10,0.92, p = 0.04, I2 = 75%] and in-hospital mortality [OR 0.63, 95%CI 0.44,0.89, p = 0.009, I2 = 0%] treated with bivalirudin were found compared with heparin. There were no significant differences between groups regarding the time to reach therapeutic levels [MD 3.53, 95%CI −4.02,11.09, p = 0.36, I2 = 49%], TTR [MD 8.64, 95%CI −1.72,18.65, p = 0.10, I2 = 77%], circuit exchanges [OR 0.92, 95%CI 0.27,3.12, p = 0.90, I2 = 38%], HIT [OR 0.25, 95%CI 0.02,2.52, p = 0.24, I2 = 0%], minor bleeding events [OR 0.93, 95%CI 0.38,2.29, p = 0.87, I2 = 0%], hospital LOS [MD −2.93, 95%CI -9.01,3.15, p = 0.34, I2 = 45%], ICU LOS [MD −4.22, 95%CI -10.07,1.62, p = 0.16, I2 = 0%], mortality [OR 1.84, 95%CI 0.58,5.85, p = 0.30, I2 = 60%] and 30-day mortality [OR 0.75, 95%CI 0.38,1.48, p = 0.41, I2 = 0%]. Conclusion: Bivalirudin probably be a potential choice for ECMO anticoagulation. However, based on the included studies’ limitation, the superiority of bivalirudin over heparin for anticoagulation in the ECMO population still require further prospective randomized controlled studies before a definite conclusion.

Summary: Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1–February 28), ii) local transmission (March 1–March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Abstract Background China is facing substantial risks of imported coronavirus disease 2019 (COVID-19) cases and a domestic resurgence in the long run, and COVID-19 vaccination is expected to be the long-lasting solution to end the pandemic. We aim to estimate the size of the target population for COVID-19 vaccination at the provincial level in the mainland of China, and summarize the current progress of vaccination programs, which could support local governments in the timely determination and adjustment of vaccination policies and promotional measures. Methods We conducted a descriptive study of the entire population in the mainland of China, between December 2020 and August 2021. By extracting provincial-stratified data from publicly available sources, we estimated the size of priority target groups for vaccination programs, and further characterized the ongoing vaccination program at the provincial level, including the total doses administered, the coverage rate, and the vaccination capacity needed to achieve the target coverage of 80% by the end of 2021. We used R (version 4.1.0) to complete the descriptive statistics. Results The size of the target population shows large differences among provinces, ranging from 3.4 million to 108.4 million. As of 31 August, 2021, the speed of vaccine roll-out differs considerably as well, with the highest coverage occurring in Beijing and Shanghai, where 88.5% and 79.1% of the population has been fully vaccinated, respectively. In 22 of 31 provincial-level administrative divisions (PLADs), more than 70% of the population was administered at least one dose by August. With the current vaccination capacity, the target of 80% coverage could be achieved by 2021 in 28 PLADs. Conclusions Disparities exist in the target population size and vaccination progress across provinces in the mainland of China. China has made great strides in the vaccination speed since roll-out, and could basically achieve the targeted vaccine coverage. Graphic Abstract

In the context of limited supply, strategies for optimising allocation of COVID-19 vaccines are needed. Here, the authors explore time-varying strategies that adapt to the epidemiological situation and simultaneously optimise for multiple objectives including reducing numbers of infections, hospitalisations, and deaths.

Abstract Background The rapid process of research and development and lack of follow-up time post-vaccination aroused great public concern about the safety profile of COVID-19 vaccine candidates. To provide comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique. Methods English-language articles and results posted on PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data were searched through June 12, 2021. Publications disclosing safety data of COVID-19 candidate vaccines in humans were included. A meta-analysis of proportions was performed to estimate the pooled incidence and the pooled rate ratio (RR) of safety outcomes of COVID-19 vaccines using different platforms. Results A total of 87 publications with safety data from clinical trials and post-authorization studies of 19 COVID-19 vaccines on 6 different platforms were included. The pooled rates of local and systemic reactions were significantly lower among inactivated vaccines (23.7%, 21.0%), protein subunit vaccines (33.0%, 22.3%), and DNA vaccines (39.5%, 29.3%), compared to RNA vaccines (89.4%, 83.3%), non-replicating vector vaccines (55.9%, 66.3%), and virus-like particle vaccines (100.0%, 78.9%). Solicited injection-site pain was the most common local reactions, and fatigue and headache were the most common systemic reactions. The frequency of vaccine-related serious adverse events was low (< 0.1%) and balanced between treatment groups. Vaccine platforms and age groups of vaccine recipients accounted for much of the heterogeneity in safety profiles between COVID-19 vaccines. Reporting rates of adverse events from post-authorization observational studies were similar to results from clinical trials. Crude reporting rates of adverse events from post-authorization safety monitoring (passive surveillance) were lower than in clinical trials and varied between countries. Conclusions Available evidence indicates that eligible COVID-19 vaccines have an acceptable short-term safety profile. Additional studies and long-term population-level surveillance are strongly encouraged to further define the safety profile of COVID-19 vaccines.

Detailed knowledge of COVID-19 epidemiology is needed to inform public health responses. Here, the authors use large-scale contact tracing data to provide empirical estimates of key parameters, and show that susceptibility increases with age but transmissibility does not vary significantly.

China has achieved high vaccination coverage under the Expanded Program on Immunization (EPI) in children 1–2 years of age. However, a knowledge gap exists regarding vaccination coverage and timeliness for children >2 years of age. As such, this study aimed to estimate coverage and timeliness for all EPI and selected non-EPI vaccines within a rural area of China. Immunization data for 5091 children, born between September 2003 and November 2015, were collected from vaccination cards obtained during sero-surveillance follow-up visits and/or from the Hunan immunization information system. For each dose of both EPI and non-EPI vaccines, vaccination coverage and timeliness were calculated, and temporal variations were examined across birth cohorts. We found coverage for EPI vaccines scheduled for

Abstract Background Improvements of population health in China have been unevenly distributed among different sexes and regions. Mortality Registration System provides an opportunity for timely assessments of mortality trend and inequalities. Methods Causes of death were reclassified following the method of Global Burden of Disease Study (GBD). Age-standardized mortality rate (ASMR) and ring-map of the rate by town were used to describe inequalities in changing mortality. Life expectancy (LE) and cause-deleted LE were calculated on the basis of life table technique. Results The burden of death from 2002 to 2018 was dominated by cardiovascular diseases (CVD), neoplasms, chronic respiratory diseases and injuries in Jiading district, accounting for almost 80% of total deaths. The overall ASMR dropped from 407.6/100000 to 227.1/100000, and LE increased from 77.86 years to 82.31 years. Women lived about 3.0–3.5 years longer than men. Besides, a cluster of lower LE was found for CVD in the southeast corner and one cluster for neoplasms in the southern corner of the district. The largest individual contributor to increment in LE was neoplasms, ranged from 2.41 to 3.63 years for males, and from 1.60 to 2.36 years for females. Conclusions Improvement in health was mainly attributed to the decline of deaths caused by CVD and neoplasms, but was distributed with sex and town. This study served as a reflection of health inequality, is conducive to formulate localized health policies and measures.

Abstract Background All countries are facing decisions about which population groups to prioritize for access to COVID-19 vaccination after the first vaccine products have been licensed, at which time supply shortages are inevitable. Our objective is to define the key target populations, their size, and priority for a COVID-19 vaccination program in the context of China. Methods On the basis of utilitarian and egalitarian principles, we define and estimate the size of tiered target population groups for a phased introduction of COVID-19 vaccination, considering evolving goals as vaccine supplies increase, detailed information on the risk of illness and transmission, and past experience with vaccination during the 2009 influenza pandemic. Using publicly available data, we estimated the size of target population groups, and the number of days needed to vaccinate 70% of the target population. Sensitivity analyses considered higher vaccine coverages and scaled up vaccine delivery relative to the 2009 pandemic. Results Essential workers, including staff in the healthcare, law enforcement, security, nursing homes, social welfare institutes, community services, energy, food and transportation sectors, and overseas workers/students (49.7 million) could be prioritized for vaccination to maintain essential services in the early phase of a vaccination program. Subsequently, older adults, individuals with underlying health conditions and pregnant women (563.6 million) could be targeted for vaccination to reduce the number of individuals with severe COVID-19 outcomes, including hospitalizations, critical care admissions, and deaths. In later stages, the vaccination program could be further extended to target adults without underlying health conditions and children (784.8 million), in order to reduce symptomatic infections and/or to stop virus transmission. Given 10 million doses administered per day, and a two-dose vaccination schedule, it would take 1 week to vaccinate essential workers but likely up to 7 months to vaccinate 70% of the overall population. Conclusions The proposed framework is general but could assist Chinese policy-makers in the design of a vaccination program. Additionally, this exercise could be generalized to inform other national and regional strategies for use of COVID-19 vaccines, especially in low- and middle-income countries.

Abstract Influenza causes substantial morbidity and mortality. Many original studies have been carried out to estimate disease burden of influenza in mainland China, while the full disease burden has not yet been systematically reviewed. We did a systematic review and meta-analysis to assess the burden of influenza-associated mortality, hospitalization, and outpatient visit in mainland China. We searched 3 English and 4 Chinese databases with studies published from 2005 to 2019. Studies reporting population-based rates of mortality, hospitalization, or outpatient visit attributed to seasonal influenza were included in the analysis. Fixed-effects or random-effects model was used to calculate pooled estimates of influenza-associated mortality depending on the degree of heterogeneity. Meta-regression was applied to explore the sources of heterogeneity. Publication bias was assessed by funnel plots and Egger’s test. We identified 30 studies eligible for inclusion with 17, 8, 5 studies reporting mortality, hospitalization, and outpatient visit associated with influenza, respectively. The pooled influenza-associated all-cause mortality rates were 14.33 and 122.79 per 100,000 persons for all ages and ≥ 65 years age groups, respectively. Studies were highly heterogeneous in aspects of age group, cause of death, statistical model, geographic location, and study period, and these factors could explain 60.14% of the heterogeneity in influenza-associated mortality. No significant publication bias existed in estimates of influenza-associated all-cause mortality. Children aged

Hand, foot and mouth disease (HFMD) is a common infectious disease in western Asia area and the full range of the long-term sequelae of HFMD remains poorly described. We conducted a retrospective hospital-based cohort study of HFMD patients with central nervous system (CNS) complications caused by EV-A71 or CV-A16 between 2010 and 2016. Patients were classified into three groups, including CNS only, autonomic nervous system (ANS) dysregulation, and cardiorespiratory failure. Neurologic examination, neurodevelopmental assessments, Magnetic Resonance Imaging (MRI) and lung function, were performed at follow up. Of the 176 patients followed up, 24 suffered CNS only, 133 ANS dysregulation, and 19 cardiorespiratory failure. Median follow-up period was 4.3 years (range [1.4–8.3]). The rate of neurological abnormalities was 25% (43 of 171) at discharge and 10% (17 of 171) at follow-up. The rates of poor outcome were significantly different between the three groups of complications in motor (28%, 38%, 71%) domain (p=0.020), but not for cognitive (20%, 24%, 35%), language (25%, 36%, 41%) and adaptive (24%, 16%, 26%) domains (p = 0.537, p = 0.551, p = 0.403). For children with ventilated during hospitalization, 41% patients (14 of 34) had an obstructive ventilatory defect, and one patient with scoliosis had mixed ventilatory dysfunction. Persistent abnormalities on brain MRI were 0% (0 of 7), 9% (2 of 23) and 57% (4 of 7) in CNS, ANS and cardiorespiratory failure group separately. Patients with HFMD may have abnormalities in neurological, motor, language, cognition, adaptive behaviour and respiratory function. Long-term follow-up programmes for children’s neurodevelopmental and respiratory function may be warranted.

Abstract Background Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection. Methods We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections. We assessed A(H5N1) virus antibody titers and changes in titers among populations with variable exposures to different A(H5N1) viruses. Results Across studies using the World Health Organization-recommended seropositive definition, the point estimates of the seroprevalence of A(H5N1) virus-specific antibodies were higher in poultry-exposed populations (range 0–0.6%) and persons exposed to both human A(H5N1) cases and infected birds (range 0.4–1.8%) than in close contacts of A(H5N1) cases or the general population (none to very low frequencies). Seroprevalence was higher in persons exposed to A(H5N1) clade 0 virus (1.9%, range 0.7–3.2%) than in participants exposed to other clades of A(H5N1) virus (range 0–0.5%) (p

Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC.

During January–February 2020, coronavirus disease (COVID-19) and tuberculosis were diagnosed for 3 patients in Wuhan, China. All 3 patients had COVID-19 pneumonia. One severely ill patient died after acute respiratory distress syndrome developed. Clinicians and public health officials should be aware of underlying chronic infections such as tuberculosis in COVID-19 patients.

Various interventions for live poultry markets (LPMs) have emerged to control outbreaks of avian influenza A(H7N9) virus in mainland China since March 2013. We assessed the effectiveness of various LPM interventions in reducing transmission of H7N9 virus across 5 annual waves during 2013–2018, especially in the final wave. With the exception of waves 1 and 4, various LPM interventions reduced daily incidence rates significantly across waves. Four LPM interventions led to a mean reduction of 34%–98% in the daily number of infections in wave 5. Of these, permanent closure provided the most effective reduction in human infection with H7N9 virus, followed by long-period, short-period, and recursive closures in wave 5. The effectiveness of various LPM interventions changed with the type of intervention across epidemics. Permanent LPM closure should be considered to maintain sufficient effectiveness of interventions and prevent the recurrence of H7N9 epidemics.

Abstract Background China has an aging population with an increasing number of adults aged ≥ 60 years. Influenza causes a heavy disease burden in older adults, but can be alleviated by vaccination. We assessed the cost-effectiveness of a potential government-funded seasonal influenza vaccination program in older adults in China. Methods We characterized the health and economic impact of a fully funded influenza vaccination program for older adults using China-specific influenza disease burden, and related cost data, etc. Using a decision tree model, we calculated the incremental costs per quality-adjusted life year (QALY) gained of vaccination from the societal perspective, at a willingness-to-pay threshold equivalent to GDP per capita (US$8840). Moreover, we estimated the threshold vaccination costs, under which the fully funded vaccination program is cost-effective using GDP per capita as the willingness-to-pay threshold. Results Compared to current self-paid vaccination, a fully funded vaccination program is expected to prevent 19,812 (95% uncertainty interval, 7150–35,783) influenza-like-illness outpatient consultations per year, 9418 (3386–17,068) severe acute respiratory infection hospitalizations per year, and 8800 (5300–11,667) respiratory excess deaths due to influenza per year, and gain 70,212 (42,106–93,635) QALYs per year. Nationally, the incremental costs per QALY gained of the vaccination program is US$4832 (3460–8307), with a 98% probability of being cost-effective. The threshold vaccination cost is US$10.19 (6.08–13.65). However, variations exist between geographical regions, with Northeast and Central China having lower probabilities of cost-effectiveness. Conclusions Our results support the implementation of a government fully funded older adult vaccination program in China. The regional analysis provides results across settings that may be relevant to other countries with similar disease burden and economic status, especially for low- and middle-income countries where such analysis is limited.

To determine the seroprevalence and seroconversion of avian influenza virus (AIV) antibodies in poultry workers, we conducted a seroepidemiologic study in 7 areas of China during December 2014–April 2016. We used viral isolation and reverse transcription PCR to detect AIVs in specimens from live poultry markets. We analyzed 2,124 serum samples obtained from 1,407 poultry workers by using hemagglutination inhibition and microneutralization assays. We noted seroprevalence of AIV antibodies for subtypes H9N2, H7N9, H6N1, H5N1-SC29, H5N6, H5N1-SH199, and H6N6. In serum from participants with longitudinal samples, we noted seroconversion, with >4-fold rise in titers, for H9N2, H7N9, H6N1, H5N1-SC29, H6N6, H5N6, and H5N1-SH199 subtypes. We found no evidence of H10N8 subtype. The distribution of AIV antibodies provided evidence of asymptomatic infection. We found that AIV antibody prevalence in live poultry markets correlated with increased risk for H7N9 and H9N2 infection among poultry workers.

IntroductionThe clinical performance of [–2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) has been well evaluated in prostate biopsy patients. However, no study has been performed to evaluate the common genetic determinants that affect serum level of p2PSA.Materials and MethodsHere, we performed a two-stage genome-wide association study (GWAS) on the p2PSA level in Chinese men who underwent a transperineal ultrasound-guided prostate biopsy at Huashan Hospital, Shanghai Cancer Center, and Ruijin Hospital in Shanghai, China. Germline variants significantly associated with the p2PSA level in the first stage (n = 886) were replicated in the second stage (n = 1,128). Multivariate linear regression was used to assess the independent contribution of confirmed single nucleotide polymorphisms (SNPs) and known covariates, such as age, to the level of p2PSA.ResultsA novel non-synonymous SNP, rs72725879, in region 8q24.21 of the PRNCR1 gene was significantly associated with the serum level of p2PSA in this two-stage GWAS (p = 2.28 × 10−9). Participants with homozygous “T” alleles at rs72725879 had higher p2PSA levels compared to allele “C” carriers. This variant was also nominally associated with PCa risk (p-combined = 3.44 × 10−18). The association with serum level of p2PSA was still significant after adjusting for PCa risk and age (p = 0.017).ConclusionsOur study shows that the genetic variants in the 8q24.21 region are associated with the serum level of p2PSA in a large-scale Chinese population. By taking inherited variations between individuals into account, the findings of these genetic variants may help improve the performance of p2PSA in predicting prostate cancer.