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Global Cancer Statistics for 2020 show that urinary system tumors account for approximately 13% of the total number of cancers. At present, the diagnostic methods of urinary system tumors are imaging, endoscopy, and pathological examination. As the gold standard of tumor diagnosis, pathological examination has problems such as lack of pathologists and long operation time. Artificial intelligence (AI), with a strong ability for pathology image recognition and feature analysis, can be used as an auxiliary diagnosis. It has realized automatic diagnosis, typing, staging, grading, and prognosis prediction in several urinary system tumors. However, AI still has many shortcomings, which limit its clinical application. This article will review the progress of AI and its application in the pathological study of urinary system tumors.
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The incidence of bladder cancer is increasing annually, and the gold standard for its diagnosis relies on histopathological biopsy. Whole-slide digitization technology can produce thousands of high-resolution captured pathological images and has greatly promoted the development of digital pathology. Deep learning, as a new method of artificial intelligence, has achieved remarkable results in the analysis of pathological images for tumor diagnosis, molecular typing, and prediction of prognosis and recurrence of bladder cancer. Traditional pathology relies heavily on the professional level and experience of pathologists; as such, it is highly subjective and has poor reproducibility. Deep learning can automatically extract image features. It can also improve diagnostic efficiency and repeatability and reduce missed and misdiagnosed rates when used to assist pathologists in making decisions. This technology cannot only alleviate the pressure of the current shortage of skilled workforce and uneven medical resources but also promote the development of precision medicine. This article reviews the latest research progress and prospects of deep learning in pathological image analysis of bladder cancer.
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Objective:To investigate the knowledge, attitude and practice of general practitioners (GPs) in Shenzhen towards managing patients with common mental health problems.Methods:It was a cross-sectional study, from September 19 to October 31, 2020, 500 GPs from 100 community health centers (CHC) in 10 districts of Shenzhen municipality were randomly selected as the research subjects by stratified random sampling; the survey was conducted by self-filled questionnaire, which included general conditions, knowledge tests of common psychological problems (generalized anxiety disorder, depressive disorder, panic attacks, sleep disorders), GPs′ attitudes to take care of common psychological problems, and GPs′ practice of caring for common psychological problems.Results:A total of 500 questionnaires were distributed and 329 valid ones were collected. In terms of knowledge, GPs had the highest accuracy of answering the characteristics of depressive disorder (97.3%, 320/329), and the lowest accuracy of case analysis of panic attacks (50.2%, 165/329). In terms of attitude, 71.1%(234/329)of GPs agreed that "common psychological problems should be taken care of",there was a statistically significant difference in attitude scores among GPs with different years of working in CHC ( Z=14.60, P=0.006). In terms of practice, the most encountered mental health problem was insomnia (91.2%, 300/329), 46.5% (153/329) of GPs would use psychological assessment scales, 52.9% (174/329) of GPs would choose direct referral, and there were statistically significant differences in attitude scores among GPs with different years of working ( Z=10.70, P=0.030) and years of working in CHC ( Z=22.14, P<0.001). Conclusions:GPs have a positive attitude in taking care of common psychological problems, but lack of knowledge and confidence. As working in CHC for more years, GPs are more inclined to care for patients with common psychological problems in practice.
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BackgroundIn 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. MethodsWe extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological 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). FindingsA surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) 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. The spatial distribution of the infections was highly heterogeneous, with 40% 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 544 to 325 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. InterpretationOur 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 successfully containing Omicron outbreaks. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSOn May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak. Added value of this studyWe collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China. Implications of all the available evidenceThis descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.
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BackgroundHundreds of millions of doses of COVID-19 vaccines have been administered globally, but progress in vaccination varies considerably between countries. We aim to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. MethodsWe conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 23 October 2021. 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. FindingsUse of both mRNA and adenovirus vectored vaccines was the most commonly used COVID-19 vaccines formulary in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (176 countries). Almost all countries (98.3%, 173/176) have authorized vaccines for the general public, with 53.4% (94/176) targeting individuals over 12 years and 33.0% (58/176) targeting those [≥]18 years. Forty-one and sixty-seven countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 116.5 doses administered per 100 target population, although with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0% to more than 95.0% of country target populations, and numbers of doses administered ranged from 0 to 239.6 per 100 target population. Doses administered per 100 total population correlated with healthcare access and quality index (R2 = 0.58), socio-demographic index (R2 = 0.56), and GDP per capita (R2 = 0.65). At least 5.54 billion doses will be required to complete interim vaccination programs - 4.65 billion for primary immunization and 0.89 billion for additional/booster programs. Globally, 0.84 and 0.96 dose per individual in the target population are needed for primary immunization and additional/booster programs, respectively. InterpretationThere is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries. FundingKey Program of the National Natural Science Foundation of China, the US National Institutes of Health. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles in any language published up to October 21, 2021, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("vaccination" OR "vaccine") AND ("inequalit*" OR "inequity" OR "disparit*" OR "heterogeneity"). We also searched for dashboards associated with vaccine rollout from public websites. We identified several studies on tracking global inequalities of vaccine access, one of which constructed a COVID-19 vaccine dashboard (Our World in Data), and another that explored disparities in COVID-19 vaccination among different-income countries. However, we found no studies that depict global COVID-19 vaccination policies country-by-country and estimate demand for vaccine necessary to completely vaccinate countries designated target populations. Added value of this studyTo our knowledge, our study provides the most recent picture of COVID-19 vaccination campaigns, focusing on global vaccination policy and target-population demand. We found a diverse portfolio of vaccines in five technical platforms being administered globally, with 173 countries having authorized administration of vaccines to the general public in various age groups. We observed inter-region and inter-country heterogeneity in one-or-more-dose and full-dose coverage; countries with higher socio-demographic or health resource-related levels had higher coverage. We estimated dose-level demand for completing primary immunization programs and additional/booster dose programs separately. Implications of all the available evidenceWorldwide disparity and inequity of vaccine rollout implies that susceptibility among unvaccinated populations in some countries may impede or reverse pandemic control, especially in face of the emergence of variants and the dilemma of waning antibodies. Our findings suggest that global-level responses to the pandemic - financially, politically, and technically - are needed to overcome complex challenges that lie ahead.
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BackgroundGenomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021. Characterizing global genomic surveillance, sequencing coverage, the extent of publicly available genomic data coupled with traditional epidemiologic data can provide evidence to inform SARS-CoV-2 surveillance and control strategies. MethodsWe collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data. We divided countries into three levels of genomic surveillance and sequencing availability based on predefined criteria. We downloaded the merged and deduplicated SARS-CoV-2 sequences from multiple public repositories, and used different proxies to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants. FindingsSince the start of 2021, the COVID-19 global epidemic clearly featured increasing circulation of Alpha, which was rapidly replaced by the Delta variant starting around May 2021 and reaching a global prevalence of 96.6% at the end of July 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020, with the lowest sequencing coverage in the WHO regions of Eastern Mediterranean, South East Asia, and Africa. Across different variants, 28-52% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. More than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. InterpretationOur findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability. Research in context Evidence before this studyOn September 3, 2021, we searched PubMed for articles in any language published after January 1, 2020, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("Global" OR "Region") AND ("genomic surveillance" OR "sequencing" OR "spread"). Among 43 papers identified, few papers discussed the global diversity in genomic surveillance, sequencing, public availability of genomic data, as well as the global spread of SARS-CoV-2 variants. A paper from Furuse employed the publicly GISAID data to evaluate the SARS-CoV-2 sequencing effort by country from the perspectives of "fraction", "timeliness", and "openness". Another viewpoint paper by Case Western Reserve Universitys team discussed the impediments of genomic surveillance in several countries during the COVID-19 pandemic. The paper as reported by Campbell and colleagues used the GISAID data to present the global spread and estimated transmissibility of recently emerged SARS-CoV-2 variants. We also found several studies that reported the country-level genomic surveillance and spread of variants. To our knowledge, no research has quantitatively depicted the global SARS-CoV-2 genomic surveillance, sequencing ability, and public availability extent of genomic data. Added value of this studyThis study collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data as of 20 August 2021. We found that genomic surveillance strategies and sequencing availability is globally diverse. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020. Our analysis of publicly deposited SARS-CoV-2 sequences and officially reported number of variants implied that the public availability extent of genomic data is low in some countries, and more than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. We also described the pandemic dynamics shaped by VOCs. Implications of all the available evidenceOur study provides a landscape for global sequencing coverage and public availability extent of sequences, as well as the evidence for rapid spread of SRAS-CoV-2 variants. The pervasive spread of Alpha and Delta variants further highlights the threat of SARS-CoV-2 mutations despite the availability of vaccines in many countries. It raised an urgent need to do more work on defining the ideal sampling schemes for different purposes (e.g., identifying new variants) with an additional call to share these data in public repositories to allow for further rapid scientific discovery.
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BackgroundTo 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. MethodsWe developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. ResultsWe found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate 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 53-58% in case of an epidemic starts to unfold in the fall of 2021. ConclusionsEfforts should be taken to increase populations confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.
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BackgroundImmunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. MethodsWe systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. FindingsWe identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). InterpretationOur findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. FundingChinese National Science Fund for Distinguished Young Scholars Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSeveral newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants. Added value of this studyIn this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural-infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Implications of all the available evidenceOur findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies.
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The clinical data of 1 patient with long-term survival metastatic prostate cancer were analyzed retrospectively, and the related literature was reviewed and discussed. The patient, male, 70 years old, was admitted to the hospital in 2009 due to dysuria with lower abdominal pain for one month.Blood PSA>1 000 ng/ml. The pathology of prostate biopsy was prostatic adenocarcinoma, Gleason score was 8 points (4+ 4), and was diagnosed as prostate cancer (T 4N 0M 1b) with bone metastasis. The patient underwent combined androgen-blocked treatment(castration and bicalutamide 50mg) for four years, then progressed to mCRPC. The initial treatment was continued in the fifth year due to the absence of novel therapeutic agents, and then symptoms progressed. The regimens were adjusted successively to increased anti-androgen (castration and bicalutamide 150 mg) from Jan 2015, then switch to another anti-androgen (Flutamide 250 mg) from Aug 2015, and then withdraw the anti-androgens from Feb 2016. All these treatments showed limited benefit for a relatively short time. The t-PSA increased steadily to over 1 000 ng/ml with persistent symptoms. In April 2017, he started the treatment with the original abiraterone acetate and underwent a PSA flare-up in the following month.tPSA decreased sharply since May 2017, less than 0.02ng/ml in Aug 2017. Meanwhile, the regimen relieved the ostealgia. He could take care of himself in daily life. raditional CAB therapy can maintain PSA-free progression and symptom-free progression for several years for some metastatic prostate cancer patients. After disease progression, the increased dosage of anti-androgens, the substitution of anti-androgen, and the withdrawal of anti-androgens showed limited benefit within a short time. However, the novel hormone therapy is still effective in relieving clinical symptoms and prolonging patients' survival time.
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Objective To investigate the value of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and FibroScan in the quantitative evaluation of liver fat content in patients with chronic hepatitis B (CHB). Methods A total of 96 patients with CHB who were hospitalized in Department of Hepatology, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, from February 2017 to July 2020 were enrolled, and all patients were diagnosed based on liver pathological examination. MRI-PDFF and FibroScan were performed before surgery. According to the results of liver biopsy, the patients were divided into non-fatty liver disease group with 44 patients, mild fatty liver disease group with 33 patients, and moderate-to-severe fatty liver disease group with 19 patients. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; Bonferroni correction was also performed. The receiver operating characteristic (ROC) curve was plotted to analyze the area under the ROC curve (AUC) of hepatic fat fraction (HFF) and controllable attenuation parameters (CAP) in the diagnosis of fatty liver disease and obtain their sensitivities, specificities, and optimal cut-off values. The intraclass correlation coefficient was used to investigate the consistency of MRI-PDFF data. Results The moderate-to-severe fatty liver disease group had a significant increase in MRI-PDFF HFF compared with the non-fatty liver disease group and the mild fatty liver disease group (all P < 0.05), and the mild fatty liver disease group had a significant increase in MRI-PDFF HFF compared with the non-fatty liver disease group( P < 0.05). The moderate-to-severe fatty liver disease group had a significant increase in FibroScan CAP compared with the non-fatty liver disease group and the mild fatty liver disease group (all P < 0.05), and the mild fatty liver disease group had a significant increase in FibroScan CAP compared with the non-fatty liver disease group ( P < 0.05). In the diagnosis of mild fatty liver disease, MRI-PDFF HFF had an AUC of 0.901 ( P < 0.001), a sensitivity of 90.9%, and a specificity of 82.7% at the optimal cut-off value of 5.1%, and in the diagnosis of moderate-to-severe fatty liver disease, MRI-PDFF HFF had an AUC of 0.972 ( P < 0.001), a sensitivity of 96.1%, and a specificity of 89.5% at the optimal cut-off value of 9.7%. In the diagnosis of mild fatty liver disease, FibroScan CAP had an AUC of 0.829 ( P < 0.001), a sensitivity of 77.3%, and a specificity of 78.8% at the optimal cut-off value of 258.5 dB/m, and in the diagnosis of moderate-to-severe fatty liver disease, FibroScan CAP had an AUC of 0.830 ( P < 0.001), a sensitivity of 76.6%, and a specificity of 78.9% at the optimal cut-off value of 285.5 dB/m. Conclusion Both MRI-PDFF and FibroScan can objectively evaluate the degree of fatty liver disease in patients with CHB. MRI-PDFF HFF and FibroScan CAP can be used as noninvasive markers for the quantitative analysis of CHB with hepatic steatosis, and MRI-PDFF HFF tends to have higher diagnostic efficiency.
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BackgroundCOVID-19 vaccine prioritization and allocation strategies that maximize health benefit through efficient use of limited resources are urgently needed. We aimed to provide global, regional, and national estimates of target population sizes for COVID-19 vaccination to inform country-specific immunization strategies on a global scale. MethodsBased on a previous study of international allocation for pandemic COVID-19 vaccines, we classified the entire world population into eleven priority groups. Information on priority groups was derived from a multi-pronged search of official websites, media sources and academic journal articles. The sizes of different priority groups were projected for 194 countries globally. ResultsOverall, the size of COVID-19 vaccine recipient population varied markedly by goals of the vaccination program and geography. The general population aged <60 years without any underlying condition accounts for the majority of the total population (5.2 billion people, 68%), followed by 2.3 billion individuals at risk of severe disease, and 246.9 million essential workers which are critical to maintaining a functional society. Differences in the demographic structure, presence of underlying conditions, and number of essential workers led to highly variable estimates of target populations both at the WHO region and country level. In particular, Europe has the highest share of essential workers (6.8%) and the highest share of individuals with underlying conditions (37.8%), two priority categories to maintain societal functions and reduce severe burden. In contrast, Africa has the highest share of healthy adults, school-age individuals, and infants (77.6%), which are the key groups to target to reduce community transmission. InterpretationThe sizeable distribution of target groups on a country and regional bases underlines the importance of equitable and efficient vaccine prioritization and allocation globally. The direct and indirect benefits of COVID-19 vaccination should be balanced by considering local differences in demography and health.
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BackgroundA rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed. PurposeTo evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys. Data sourcesWe searched PubMed, Embase, Web of Science, and 4 pre-print servers for English-language papers published from December 1, 2019 to September 25, 2020. Study selectionSerological studies evaluating SARS-CoV-2 seroprevalence in humans. Data extractionTwo investigators independently extracted data from studies. Data SynthesisMost of 230 serological studies, representing tests in >1,400,000 individuals, identified were of low quality based on a standardized study quality scale. In the 51 studies of higher quality, high-risk healthcare workers had higher seroprevalence of 17.1% (95% CI: 9.9-24.4%), compared to low-risk healthcare workers and general population of 5.4% (0.7-10.1%) and 5.3% (4.2-6.4%). Seroprevalence varied hugely across WHO regions, with lowest seroprevalence of general population in Western Pacific region (1.7%, 0.0-5.0%). Generally, the young (<20 years) and the old ([≥]65 years) were less likely to be seropositive compared to middle-aged (20-64 years) populations. Seroprevalence correlated with clinical COVID-19 reports, with pooled average of 7.7 (range: 2.0 to 23.1) serologically-detected-infections per confirmed COVID-19 case. LimitationsSome heterogeneity cannot be well explained quantitatively. ConclusionsThe overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given the relatively narrow range of estimates of the ratio of serologically-detected infections to confirmed cases across different locales, reported case counts may help provide insights into the true proportion of the population infected. Primary Funding sourceNational Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).
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The pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, where a first wave of intense community transmission was cut short by interventions. Using multiple data source, we estimated the disease burden and clinical severity of COVID-19 by age in Wuhan from December 1, 2019 to March 31, 2020. We adjusted estimates for sensitivity of laboratory assays and accounted for prospective community screenings and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95%CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had higher burden than the 2009 influenza pandemic or seasonal influenza, and that clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.
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BackgroundSeveral parameters driving the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear, including age-specific differences in infectivity and susceptibility, and the contribution of inapparent infections to transmission. Robust estimates of key time-to-event distributions remain scarce as well. MethodsWe collected individual records for 1,178 SARS-CoV-2 infected individuals and their 15,648 contacts identified by contact tracing and monitoring over the period from January 13 to April 02, 2020 in Hunan Province, China. We provide descriptive statistics of the characteristics of cases and their close contacts; we fitted distributions to time-to-key-events distributions and infectiousness profile over time; and we used generalized linear mixed model to estimate risk factors for susceptibility and transmissibility of SARS-CoV-2. ResultsWe estimated the mean serial interval at 5.5 days (95%CI -5.0, 19.9) and the mean generation time at 5.5 days (95%CI 1.7, 11.6). The infectiousness was estimated to peak 1.8 days before symptom onset, with 95% of transmission events occurring between 7.6 days before and 7.3 days after the date of symptom onset. The proportion of pre-symptomatic transmission was estimated to be 62.5%. We estimated that at least 3.5% of cases were generated asymptomatic individuals. SARS-CoV-2 transmissibility was not significantly different between working-age adults (15-59 years old) and other age groups (0-14 years old: p-value=0.16; 60 years and over: p-value=0.33), whilst susceptibility to SARS-CoV-2 infection was estimated to increase with age (p-value=0.03). In addition, transmission risk was higher for household contacts (p-value<0.001), decreased for higher generations within a cluster (second generation: odds ratio=0.13, p-value<0.001; generations 3-4: odds ratio=0.05, p-value<0.001, relative to generation 1), and decreased for infectors with a larger number of contacts (p-value=0.04). InterpretationOur findings warn of the possible relevant contribution of children to SARS-CoV-2 transmission. When lockdown interventions are in place, we found that odds of transmission are highest in the household setting but, with the relaxation of interventions, other settings (including schools) could bear a higher risk of transmission. Moreover, the estimated relevant fraction of pre-symptomatic and asymptomatic transmission highlight the importance of large-scale testing, contact tracing activities, and the use of personnel protective equipment during the COVID-19 pandemic.
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We conducted two surveys to evaluate the health-seeking behaviors of individuals with acute respiratory infections (ARI) during the COVID-19 outbreak in Wuhan, China. Among 351 participants reporting ARI (10.3%, 351/3,411), 36.5% sought medical assistance. Children were more likely to seek medical assistance than other age groups (66.1% vs. 28.0%-35.1%).
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ObjectiveThe outbreak of novel coronavirus disease 2019 (COVID-19) imposed a substantial health burden in mainland China and remains a global epidemic threat. Our objectives are to assess the case fatality risk (CFR) among COVID-19 patients detected in mainland China, stratified by clinical category and age group. MethodsWe collected individual information on laboratory-confirmed COVID-19 cases from publicly available official sources from December 29, 2019 to February 23, 2020. We explored the risk factors associated with mortality. We used methods accounting for right-censoring and survival analyses to estimate the CFR among detected cases. ResultsOf 12,863 cases reported outside Hubei, we obtained individual records for 9,651 cases, including 62 deaths and 1,449 discharged cases. The deceased were significantly older than discharged cases (median age: 77 vs 39 years, p<0.001). 58% (36/62) were male. Older age (OR 1.18 per year; 95%CI: 1.14 to 1.22), being male (OR 2.02; 95%CI: 1.02 to 4.03), and being treated in less developed economic regions (e.g., West and Northeast vs. East, OR 3.93; 95%CI: 1.74 to 8.85) were mortality risk factors. The estimated CFR was 0.89-1.24% among all cases. The fatality risk among critical patients was 2-fold higher than that among severe and critical patients, and 24-fold higher than that among moderate, severe and critical patients. ConclusionsOur estimates of CFR based on laboratory-confirmed cases ascertained outside of Hubei suggest that COVID-19 is not as severe as severe acute respiratory syndrome and Middle East respiratory syndrome, but more similar to the mortality risk of 2009 H1N1 influenza pandemic in hospitalized patients. The fatality risk of COVID-19 is higher in males and increases with age. Our study improves the severity assessment of the ongoing epidemic and can inform the COVID-19 outbreak response in China and beyond.
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Objective To evaluate the effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD).Methods Thirty adult male Sprague-Dawley rats,aged 8 weeks,weighing 200-250 g,were divided into 3 groups (n=10 each) using a random number table method:control group (C group),COPD group and doxofylline group (Dox group).Rats were fed in normoxia for 2 months,and normal saline 0.2 ml was injected into the trachea on 1st and 30th days in C group.Rats were exposed to cigarette smoke for 30 min every day,lasting for 2 months,and lipopolysaccharide 200 μg (0.2 ml) was injected into the trachea on 1st and 30th days in COPD and Dox groups.Two months later,rats in each group were anesthetized,tracheally intubated,and then mechanically ventilated.Doxofylline 50 mg/kg was intravenously injected immediately after intubation in Dox group,and the equal volume of normal saline was given instead in C and COPD groups.Pulmonary specimens were taken after 120 min of mechanical ventilation for examination of pathological changes and for determination of wet/dry weight ratio (W/D ratio) and tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) contents (by enzyme-linked immunosorbent assay).Results No significant pathological change of lung tissues was found in C group,and COPD pathological changes were observed in COPD and Dox groups.Compared with C group,the W/D ratio and TNF-α level were significantly increased,and the IL-10 level was decreased in COPD and Dox groups (P＜0.05).Compared with COPD group,the W/D ratio and TNF-α level were significantly decreased,and the IL-10 level was increased in Dox group (P＜0.05).Conclusion Doxofylline can reduce the pulmonary inflammatory response induced by mechanical ventilation in rats with COPD.
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Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high-throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways—the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion, 'whether to do it’, ten years ago, the question, 'how to do it’, has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi-disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.
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Objective To investigate the effect of neuropilin-1 (NRP1) on radiation-induced epithelial-mesenchymal transition (EMT) by measuring the expressions of EMT-related transcription factors in the irradiated cells with different levels of NRP 1.Methods Human lung type Ⅱ epithelial cells (A549) were transfected with NRP1 over-expression lentiviral vector and NRP1 inhibition vector to construct two cell models of NRP1high-A549 and NRP1low-A549.A NRP1 knock-down cell model was also constructed by transferring siNRP1 into normal mouse lung epithelial MLE-12 cells that was validated at both protein and mRNA levels.A single dose of 10 Gy X-ray was delivered to these cell models,then total protein and RNA were extracted at 0,12,24 and 48 h after irradiation.The expressions of EMT-related transcription factors (Twist and ZEB1) and EMT markers (β3-catenin,N-cadherin,and Vimentin) in each cell model were detected by Western blot and qPCR.Results After 10 Gy irradiation,the expressions of NRP1 mRNA and protein were significantly increased in A549 and MLE-12 cells.The expressions of the mesenchymal markers (Vimentin and N-cadherin) and the transcription factors of ZEB1 and Twist were also significantly increased (A549:t=2.917,7.361,4.852,9.278,P＜0.01;MLE-12:t=9.652,31.357,30.985,17.266,P ＜0.01).The expressions of Vimentin and N-cadherin were significantly decreased in NRP1low-A549 (t =10.077,15.707,P ＜ 0.01) and siNRP1-MLE-12 cells (t =5.745,P ＜ 0.01),but the expression of epithelial marker (β3-catenin) was significantly increased in these cells.The expressions of N-Cadherin and Vimentin were significantly elevated (t =16.055,5.560,P ＜ 0.01),while β-catenin decreased significantly in NRP1high-A549 cells.After irradiation,the transcription factor of Twist in NRP1low-A549 group was significantly decreased (t=3.987,P＜0.01),while the transcription factors of ZEB1 and Twist in the NRP1high-A549 group increased in a time-dependent manner (t =11.289,2.903,P＜0.01).After irradiation,the transcription factor of ZEB1 decreased significantly in siNRP1-MLE-12 cells (t=13.449,P＜0.01),and the protein expressions of ZEB1 and Twist in siNRP1-MLE-12 cells were lower than those of control group in a time-dependent manner.Conclusions NRP1 promotes radiation-induced EMT in human and mouse epithelial cells through up-regulation of transcription factors of ZEB1 and Twist.
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Objective To explore the value of prostate specific antigen density (PSAD) in clinical decision making for patients with prostate imaging reporting and data system version 2 (PI-RADS v2) category 3 lesions.Methods Totally 54 patients with PI-RADS v2 category 3 lesions who underwent prostate biopsy before MRI were enrolled and divided into prostate cancer (PCa) group (n=11) and benign group (n=43) according to biopsy results.Then clinical data and imaging features,including total prostate specific antigen (TPSA),free prostate specific antigen (FPSA),FPSA/TPSA ratio (F/T),PSAD,prostate volume and the volume of index lesion were collected and statistically analyzed between the two groups.ROC curve was used to evaluate the diagnostic efficacy of PSAD in predicting malignant and benign lesions in patients with PI RADS v2 category 3 lesions.Results PSAD had statistical difference (P=0.006),whereas TPSA,FPSA,F/T,prostate volume and the volume of index lesion showed no statistical differences between PCa group and benign group (all P＞0.05).ROC curves showed that area under the curve was 0.771(P＜0.05).Using the optimal threshold of PSAD-0.25 ng/ml2,the sensitivity and specificity of PSAD in predicting PCa and benign lesions was 72.73 ％ (8/11) and 74.42％(32/43),respectively.Conclusion PSAD is an effective index to predict the risk of PCa in patients with PI-RADS v2 category 3 lesions.Using the threshold of PSAD=0.25 ng/ml2 to screen high risk patients for prostate biopsy,the positive rate could be improved and unnecessary biopsies could be avoided.
