Subtypes In China Research Articles

Construction and immunological evaluation of recombinant adenovirus vaccines of new novel NADC34-PRRSV strains in pigs

IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive and respiratory diseases in sow herds and piglets. The emergence of ORF5 RFLP 1–7-4-like (NADC34-like) PRRSV strain in China has brought a new round of challenges to PRRSV prevention.MethodsIn addition, recombinant adenovirus vaccine candidates against the newly emerged NADC34-like strain were constructed in the study; the immunogenicity of the vaccine was investigated in piglets. After inoculation with PRRSV recombinant adenovirus, specific antibodies, neutralizing antibodies, and levels of IFN-γ and IL-4 cytokines were detected in serum.ResultsThirty-five days after immunization, the levels of IFN-γ and IL-4 cytokines in the pac-Ad5-34-GP3, pac-Ad5-34-GP5, and pac-Ad5-34-GP35 experimental groups were significantly higher (p < 0.05) than those of the PBS and the adenovirus group. All vaccines can cause corresponding Th1 and Th2 immune responses based on animal experimental results. After the challenge, no obvious clinical symptoms were observed in the immune groups compared with the control group, vaccinated animals could reduce the occurrence of viremia, and the occurrence of viremia was alleviated, with no obvious pathological changes in the lungs, indicating that recombinant adenovirus vaccine could provide a good protective immunity and produce a good humoral and cellular immune response at the same time.DiscussionIt shows that the recombinant adenovirus vaccine group has better protection against the virus. Provide vaccine reserve and theoretical support for the emergence of new PRRSV subtypes in China.

Urban-rural disparities in mortality due to stroke subtypes in China and its provinces, 2015-2020.

Death burden of stroke is severe in China with over one-third rural residents, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke (IS) increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of IS ASMR make rural males the focus of stroke management. The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.

Characterization of Two Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Among Men Who Have Sex with Men and Mother-to-Child Transmission Cases in Baoding City, China.

CRF01_AE and CRF07_BC are predominant circulating HIV-1 subtypes in China. In this study, we report two novel HIV-1 CRF01_AE/CRF07_BC recombinant forms isolated from one man who has sex with men (MSM) (BDD027) and one mother-to-child transmission (MTCT) case (BDL123) in Baoding City, Hebei Province, China. The recombination breakpoint analysis showed that the recombination pattern of the near-full-length genome of BDD027 consisted of two CRF07_BC fragments inserted into a CRF01_AE backbone, while the recombination pattern of the near-full-length genome of BDL123 consisted of one CRF01_AE fragment inserted into a CRF07_BC backbone. This study demonstrates the importance of strengthening the monitoring of HIV-1 molecular epidemiological characteristics and emphasizes the urgent need to reduce the HIV-1 epidemic among MSM and MTCT populations in China.

Exploring disparities in HIV-1 pretreatment and acquired drug resistance in China from 2003 to 2022.

To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China. HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database. A total of 36 263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions. HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.

Long-term outcomes among ischemic stroke TOAST subtypes: A 12-year Cohort study in China

BackgroundDisparities in short-term ischemic stroke (IS) prognosis among Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes were observed. Notably, little is known about the long-term prognosis of different subtypes in China. We aim to investigate the long-term outcome in IS patients and try to explore the potential interactive effects between IS subtypes and antithrombotic therapy. MethodsThis is a prospective cohort of stroke survivors. Patients diagnosed with first-ever IS at the Department of Neurology, West China Hospital, Sichuan University from January 2010 to December 2019 were recruited. They were followed until September 2022 to assess recurrence, mortality, and functional recovery. The multivariate Fine-Gray model assessed stroke recurrence, while Cox regression estimated hazard ratios. Modified Rankin Scale scores(mRS) were analyzed using the generalized linear mixed effects model. ResultsAt baseline, 589 of 950 participants (62.00 %) were male. The longest follow-up was 150 months, the shortest was 1.5 months, and the median follow-up was 81.0 months. Cardio-embolism (CE) bore the highest mortality risk compared to large artery atherosclerosis (LAA) (HR=4.43,95 %CI 1.61-12.23). Among survivors on anticoagulant therapy, CE exhibited a reduced risk of mortality (HR = 0.18, 95 % CI 0.04-0.80). In function recovery, small artery occlusion (SAO) demonstrated more favorable prognostic outcomes (β=-2.08, P<0.01, OR=0.13,95 %CI 0.03-0.47). Among survivors taking antiplatelet drugs, SAO demonstrated a slower pace of functional recovery compared to LAA (β=1.39, P=0.05, OR=3.99,95 %CI 1.01-15.74). ConclusionsLong-term outcomes post-first IS vary among TOAST subtypes. Anticoagulant therapy offers long-term benefits among patients of the CE. However, prolonged administration of antiplatelet drugs among SAO patients may be limited in improving function recovery. Physicians should carefully consider treatment options for different IS subtypes to optimize patient outcomes and stroke care effectiveness.

Predictive value of fluorometric method and tandem mass spectrometry for hyperphenylalaninemia and its subtypes in China: A systematic review and meta‑analysis.

The present study aimed to conduct a comprehensive meta-analysis to assess the diagnostic value of fluorometric assays and tandem mass spectrometry (MS/MS) for hyperphenylalaninemia (HPA) and its subtypes. The PubMed, Embase and Cochrane Library databases were searched from inception to October 2023. The present study included studies that reported the newborn screening and genetic features of patients with HPA and excluded duplicate publications, studies without full text, studies with incomplete information, studies from which it was not possible to extract data, animal experiments, reviews and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results revealed that 0.04% [95% confidence interval (CI): 0.019-0.069] of neonatal HPA fluorometric assays and MS/MS. The positive predictive value (PPV) of neonatal HPA screening using fluorometric assays and tandem mass spectrometry was 31.7% (95% CI: 19.6-45.2). Notably, the PPV of neonatal HPA screening using fluorometric assays was 8.3% (95% CI: 7.1-9.6), while the PPV of neonatal HPA screening using tandem mass spectrometry was 31.8% (95% CI: 16.4-49.4). Additionally, the pooled results showed that the incidence of tetrahydrobiopterin deficiency (BH4D) in HPA patients was 12.43% (95% CI: 3.28-25.75) and the incidence of phenylalanine hydroxylase deficiency (PAHD) in HPA patients was 88.65% (95% CI: 78.84-95.86). Newborn screening is an effective method for the early detection of HPA and MS/MS has a greater PPA than fluorometric assays for diagnosing HPA. In addition, in the screening of HPA, the proportion of HPA patients with PAHD was significantly higher than that of patients with BH4D.

Near Full-Length Genome Characterization of Two Novel Unique Recombinants (CRF01_AE/CRF07_BC) in Beijing, China.

With the prevalence of human immunodeficiency virus type 1 (HIV-1) CRF01_AE and CRF07_BC subtypes in China, the co-circulation of multiple subtypes in the HIV-1-positive population may result in dual infection or superinfection in the population, leading to the emergence of unique recombinant forms (URFs) of the HIV-1 virus. In this study, two second-generation unique recombinant strains, BI0114 and BI0116, were identified, and their near full-length genome sequences were obtained. Recombination analysis showed that both sequences were isoforms of URF_0107, and they were second-generation unique recombinant strains formed by the recombination of CRF01_AE and CRF07_BC, with the isoforms being CRF01_AE and CRF0107_BC, respectively. The continued emergence of novel CRF01_AE/CRF07_BC recombinant strains suggests that the epidemiological, preventive, and control situation of HIV-1 is complex and that the relevant health authorities urgently need to establish responses to the challenges posed by changes in the pattern of strain recombination.

One-Health Challenge in H9N2 Avian Influenza: Novel Human-Avian Reassortment Virus in Guangdong Province, China

China is one of the highest producers of poultry meat output in the world, with a large scale of chicken rearing. Statistically analyzed H9N2-subtype avian influenza viruses (AIVs) have become the dominant subtype in China’s live poultry market, with the highest detection rate. Although H9N2 AIV is of low pathogenicity and tends not to cause serious disease and high mortality in poultry, it poses a great challenge to the domestic poultry farming industry by causing a decrease in appetite, a decline in egg production, and deaths caused by mixed infections with another pathogenic microorganism. Moreover, novel influenza viruses (H7N9 and H3N8) infecting humans have emerged in China, and the H9N2 AIV provides all or part of the internal genes to the new recombinant viruses, posing a potential threat to public health and safety and human health. In this research, six H9N2 AIVs were isolated from feces or oropharyngeal swabs collected from live poultry markets and duck farms in Zhanjiang. After epidemiological investigations, phylogenetic analyses, and molecular characterization, we found that the ZJ81 strain was a chicken–human–mink recombinant virus, the ML3 strain was a chicken-human recombinant virus, and all six virus strains of the virus had a bias for the human receptor-binding site and a mutation that could cause an increase in virulence in mice. Therefore, surveillance and control of H9N2 AIV should be strengthened to provide data support for cross-species transmission of H9N2 AIV.

Epidemiology of biliary tract cancer in China: A narrative review.

Biliary tract cancer (BTC) is a group of rare malignancies that affect the gallbladder and bile ducts. Although rare, BTC is becoming a significant public health burden in China, particularly among males and older individuals. The increasing trends in BTC incidence and mortality in China are influenced by various demographic, environmental, and lifestyle factors. In this review, we examine available epidemiological data on the incidence, mortality, prognosis, and trends of different BTC subtypes in China. We also discuss the challenges and opportunities for improving the prevention, diagnosis, and management of BTC in China, and identify areas for further research and intervention. The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.

Codon usage and evolutionary dynamics of genetic diversity of novel imported porcine reproductive and respiratory syndrome virus in China

Porcine reproductive and respiratory syndrome (PRRS) is a problem that has significant economic impact on the global pig industry. In recent years, there has been an increased importation of pork into China, contributing to the emergence of novely imported porcine reproductive and respiratory syndrome virus (PRRSV) sub-types. Nevertheless, codon usage patterns and their effects on the evolution and adaptation of these new input PRRSV sub-types in hosts remain elusive. To investigate this, we employed a Bayesian approach to analyze two novel imported PRRSV sub-types, namely, NADC30-like and NADC34-like viruses. These sub-types have different codon preferences. Besides, the Effective Number of Codon (ENC) analysis revealed that both NADC30-like and NADC34-like fall within the expected curve distribution, describing a balanced codon usage for both NADC30-like and NADC34-like virus. Based on the Codon Adaptation Index (CAI), NADC30-like showed the highest similarity to the host, aligning with the main prevalence trend of the host. In contrast, NADC34-like exhibited the highest frequency of optimal codon usage; this analysis is based on Frequency of Optimal Codons (FOP). Moreover, the Relative Codon Deoptimization Index (RCDI) indicates that NADC30-like sub-types have a greater degree of inverse optimization sub-type. These findings suggest that mutational pressure affects codon usage preferences of genes in newly imported PRRSV, and that natural selection plays a vital role in determining PRRSV gene codon preferences. Our study provides new insights into the disease, origin, evolutionary patterns, and host adaptation of these newly imported PRRSV sub-types in China. It also contributes to the development of theoretical frameworks for studying genetics and the evolution of PRRSV.

Serological and molecular analysis of the B(A) subtype in China-A systematic review.

To study the serological and molecular biological characteristics of the B(A) subtype and its geographical distribution in China through case discussion and systematic review. A case of the B(A)02 subtype previously found in our laboratory was retrospectively analysed. The distribution characteristics and specific serological and genotypic characteristics of the B(A) subtype in China were systematically evaluated by searching four major Chinese databases. In a previous case of an abnormal blood group, both the proband and her father were found to be genotype B(A)02/O02, while the mother was normal type B. After a systematic search, irrelevant studies were screened out, and 88 studies were included for analysis. The results showed that the B(A)04 subtype was significantly more frequently reported in the north than in the south, while the B(A)02 subtype was predominant in the southwest. The A antigen of the B(A)02 subtype reacts with monoclonal anti-A reagents in a wide range, while the A antigen of the B(A)04 subtype has a weak agglutination intensity of less than or equal to 2+. The results showed that the B(A) subtype has specific characteristics in the Chinese population, and this study further enriched the serological and molecular biological characteristics of the B(A) subtype.

Disease burden based on gender and age and risk factors for stroke in China, 2019.

Stroke has become the leading cause of death and disability among adults in China. This study aims to analyze the disease burden based on gender and age and the risk factors for stroke subtypes in China 2019, and to provide reference for targeted stroke prevention and control. Based on 2019 data of the Global Burden of Disease (GBD), the gender and age in patients with different stroke subtypes (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage) in China 2019 was described by using disability-adjusted life years (DALY), and attributable burden of related risk factors was analyzed. In 2019, the burden of intracranial hemorrhage was the heaviest one in China, resulting in 22.210 6 million person years of DALY, following by ischemic stroke and subarachnoid hemorrhage, resulting in 21.393 9 and 2.344 7 million person years of DALY, respectively. Among them, except the 0-14 age group, the disease burden of different subtypes of stroke in men was higher than that in women. The disease burden of ischemic stroke was increased with age in both men and women, with the heaviest disease burden in ≥70 years group. The disease burden of intracranial hemorrhage and subarachnoid hemorrhage was the heaviest in males aged 50-69 years old, and in females aged ≥70 years and 50-69 years, respectively. Metabolic factors were the main risk factors in all ages of different stroke subtypes, and the most important risk factor was high systolic blood pressure. Other risk factors were different between men and women. Smoking, high body mass index, high low-density lipoprotein, and outdoor particulate matter pollution were the main risk factors for stroke in men, while high body mass index, outdoor particulate matter pollution, and high fasting blood glucose were the main risk factors of stroke in women. The main risk were different among different age groups. The burden and attributable risk factors for different stroke subtypes are discrepancy in different gender and age groups. Targeted interventions should be conducted in the future to reduce the burden of stroke.

Association of physical activity with risk of chronic kidney disease in China: A population-based cohort study

BackgroundInformation on the association between physical activity (PA) and the risk of chronic kidney disease (CKD) is limited. We aimed to explore the associations of total, domain-specific, and intensity-specific PA with CKD and its subtypes in China. MethodsThe study included 475,376 adults from the China Kadoorie Biobank aged 30–79 years during 2004–2008 at baseline. An interviewer-administered questionnaire was used to collect the information about PA, which was quantified as metabolic equivalent of task hours per day (MET-h/day) and categorized into 4 groups based on quartiles. Cox regression was used to analyze the association between PA and CKD risk. ResultsDuring a median follow-up of 12.1 years, 5415 incident CKD cases were documented, including 1159 incident diabetic kidney disease (DKD) cases and 362 incident hypertensive nephropathy (HTN) cases. Total PA was inversely associated with CKD risk, with an adjusted hazard ratio (HR, 95% confidence interval (95%CI)) of 0.83 (0.75–0.92) for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile. Similar results were observed for risk of DKD and HTN, and the corresponding HRs (95%CIs) were 0.75 (0.58–0.97) for DKD risk and 0.56 (0.37–0.85) for HTN risk. Increased nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD, with HRs (95%CIs) of 0.80 (0.73–0.88), 0.85 (0.77–0.94), and 0.85 (0.76–0.95) in the highest quartile, respectively. ConclusionPA, including nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA, was inversely associated with the risk of CKD, including DKD, HTN, and other CKD, and such associations were dose dependent.

Secular trend in disease burden of leukemia and its subtypes in China from 1990 to 2019 and its projection in 25years.

Leukemia and its subtypes impose a major public health challenge in China. Identifying the secular trend of leukemia burden is critical to facilitate optimal healthcare planning and improve the management of leukemia. The incidence rates of leukemia from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database according to the following: subtype (acute lymphocytic leukemia [ALL], acute myeloid leukemia [AML], chronic lymphocytic leukemia [CLL], chronic myelogenous leukemia [CML], and other leukemia subtypes), sex, and age group. The average annual percentage changes and relative risks were calculated using joinpoint regression and the age-period-cohort model, respectively. The Bayesian age-period-cohort model was also applied to predict the future trend of the incidence of leukemia and its subtypes in the next 25years. From 1990 to 2019, the age-standardized incidence rates (ASIRs) of leukemia slightly declined in males and females, which is similar to the trend of other leukemia subtypes. However, the four major leukemia subtypes, namely, ALL, AML, CLL, and CML, have been on the rise over the past three decades. The incidence rates of leukemia in children and the elderly were considerably higher than those in other age groups in males and females. Age effects were the most influential risk factor for leukemia incidence. Period effects showed that the risks of leukemia and its subtypes incidence increased with time. For cohort effects, the risks of leukemia and its subtypes were higher among the early-born cohorts compared with the late-born cohorts. The ASIRs of leukemia and its subtypes will continue to increase in the next 25years. The burden of leukemia and its subtypes is expected to continue to increase in the next 25years in males and females. A comprehensive understanding of the risk characteristics and disease pattern of leukemia and its subtypes is needed to formulate timely and effective intervention measures to reduce the leukemia burden in China.

PCR73 Health-Related Quality of Life and Economic Burden in Chinese Patients with Cutaneous T-Cell Lymphoma (CTCL) – Results from Interim Analysis

Little is known about health-related quality of life (HRQoL) and economic burden in Chinese patients with cutaneous T-cell lymphoma (CTCL). This study aimed to measure the overall HRQoL and economic burden of CTCL patients with mycosis fungoides (MF) and Sezary syndrome (SS) subtypes in China.

Disparities in stage at diagnosis among breast cancer molecular subtypes in China.

Disease stage at diagnosis and molecular subtypes are the main determinants of breast cancer treatment strategies and prognosis. We aimed at examining the disparities and factors associated with the stage at diagnosis among the molecular subtypes in breast cancer patients in China. We identified patients with first primary breast cancer diagnosed between January 1, 2016, and December 31, 2017, from 23 hospitals in 12 provinces in China. We analyzed the proportion of non-early-stage (stages II-IV) breast cancer cases based on the family history of breast cancer, body mass index (BMI), insurance status, and molecular subtypes. Multivariable analyses were used to estimate the factors associated with non-early-stage diagnosis among the molecular subtypes. We further compared these estimates with that in the United States using the Surveillance, Epidemiology, and End Results database. A total of 9398 Chinese were identified with first primary invasive breast cancer. Of the 8767 patients with known stages, the human epidermal growth factor receptor 2 (HER2)-enriched subtype had the highest proportion of stages II-IV (76.6%) patients, followed by triple-negative breast cancer (73.2%), luminal B (69.9%), and luminal A (62.3%). The percentage of non-early-stage patients was higher in women with overweight or obesity than in those with a body mass index (BMI) <25 kg/m2 (adjusted odds ratio [OR] 1.3, 95% confidence interval (CI) 1.1-1.4). Patients with a family history of breast cancer had a higher likelihood of early-stage (adjusted OR 0.7, 0.5-0.8) breast cancer. Patients with rural insurance had a substantially higher risk of non-early-stage disease than those with urban insurance (adjusted OR 1.8, 1.4-2.2). Regarding the subtype, being overweight/obese only increased the risk of non-early-stage in luminal A breast cancer. Compared with the United States, China had a higher proportion of non-early-stage breast cancer for all subtypes, with the largest gap in luminal A (adjusted OR 2.2, 95% CI 2.0-2.4). The wide disparities in stage at breast cancer diagnosis imply that China urgently needs to improve early breast cancer diagnosis and health equity.

Differences in right ventricular function and response to targeted therapy between patients with IPAH and PAH-CHD.

Background and aims: Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disorder characterized by elevated pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP). Right heart failure is a life-threatening complication of PAH and predicts a poor prognosis. PAH associated with congenital heart disease (PAH-CHD) and idiopathic PAH (IPAH) are two prevalent PAH subtypes in China. In this section, we set out to explore baseline right ventricular (RV) function and its response to targeted agents between IPAH and PAH-CHD. Methods and results: Consecutive patients diagnosed with IPAH or PAH-CHD by right heart catheterization (RHC) in the Second Xiangya Hospital from November 2011 to June 2020 were included. All patients received PAH-targeted therapy and the RV function was assessed by echocardiography at baseline and during follow-up. A total of 303 patients (age, 36.23 ± 13.10years; women, 213 (70.3%); mean PAP [mPAP], 63.54 ± 16.12mmHg; PVR, 14.74 ± 7.61WU) with IPAH (n = 121) or PAH-CHD (n = 182) were included in this study. Compared with PAH-CHD, patients with IPAH had worse baseline RV function. As of the latest follow-up, forty-nine patients with IPAH and six patients with PAH-CHD died. Kaplan-Meier analyses showed better survival in PAH-CHD versus IPAH. After PAH-targeted therapy, patients with IPAH had less improvement in 6MWD, World Health Organization functional class, and RV functional parameters compared with patients with PAH-CHD. Conclusion: Compared with patients with PAH-CHD, patients with IPAH had worse baseline RV function, unfavourable prognosis, and inadequate response to targeted treatment.

Association of Urinary Zinc Concentrations with Dyslipidemia and Its Subtypes: Baseline Data from the Chinese Multi-Ethnic Cohort (CMEC) Study.

This study elucidates the association between urinary zinc concentration and the risk of developing dyslipidemia and its subtypes in China's ethnic minority residents. Based on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 10,620 subjects were included in the study. Logistic regression analysis evaluated the relationship between urinary zinc concentration and dyslipidemia and its subtypes. After adjustment, compared with urinary zinc concentration quartile 1 (Q1), the odds ratios (ORs) and 95% confidence intervals (95% CIs) of dyslipidemia participants in the quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4) groups were 1.091 (0.963, 1.237), 1.151 (1.051, 1.304), and 1.393 (1.230, 1.579), respectively (P for trend < 0.001). While that of hypertriglyceridemia participants in the Q2, Q3, and Q4 groups were 1.130 (0.979, 1.306), 1.283 (1.113, 1.480), and 1.483 (1.287, 1.709), respectively (P for trend < 0.001). Lastly, the ORs and 95% CIs of hyperbetalipoproteinemia participants in the Q2, Q3, and Q4 groups were 1.166 (0.945, 1.439), 1.238 (1.007, 1.522), and 1.381 (1.126, 1.695), respectively (P for trend < 0.002). This study found that urinary zinc concentrations were not associated with hypercholesterolemia and hypoalphalipoproteinemia. The dose-response relationship was non-linear between urinary zinc concentration and dyslipidemia, hypertriglyceridemia and hyperbetalipoproteinemia (P for trend < 0.001). In the stratified analysis, urinary zinc levels were positively associated with the risk of dyslipidemia, hypertriglyceridemia, and hyperbetalipoproteinemia in male, ≥ 60years old, Miao nationality, hypertension, diabetes, and BMI ≥ 24.0kg/m2 subgroups. Our study provides some possible evidence that elevated urinary zinc concentrations are associated with an increased risk of dyslipidemia, hypertriglyceridemia, hyperbetalipoproteinemia.

Enhanced pathogenicity and transmissibility of H9N2 avian influenza virus in mammals by hemagglutinin mutations combined with PB2-627K

H9N2 avian influenza viruses (AIVs) circulate globally in poultry and have become the dominant AIV subtype in China in recent years. Previously, we demonstrated that the H9N2 virus (A/chicken/Eastern China/SDKD1/2015) naturally harbors a mammalian-adaptive molecular factor (627K) in the PB2 protein and is weakly pathogenic in mice. Here, we focused on new markers for virulence in mammals. A mouse-adapted H9N2 virus was serially passaged in mice by infecting their lungs. As expected, infected mice showed clinical symptoms and died at passage six. A comparison between the wild-type and mouse-adapted virus sequences identified amino acid substitutions in the hemagglutinin (HA) protein. H9N2 viruses with the T187P ​+ ​M227L double mutation exhibited an increased affinity to human-type (SAα2,6Gal) receptors and significantly enhanced viral attachment to mouse lung tissues, which contributed to enhancing viral replication and virulence in mice. Additionally, HA with the T187P ​+ ​M227L mutation enabled H9N2 viral transmission in guinea pigs via direct contact. AIV pathogenicity in mice is a polygenic trait. Our results demonstrated that these HA mutations might be combined with PB2-627K to significantly increase H9N2 virulence in mice, and this enhanced virulence was achieved in other H9N2 AIVs by generating the same combination of mutations. In summary, our study identified novel key elements in the HA protein that are required for H9N2 pathogenicity in mice and provided valuable insights into pandemic preparedness against emerging H9N2 strains.

High infectivity and unique genomic sequence characteristics of Cryptosporidium parvum in China

Zoonotic Cryptosporidium parvum infections are mainly caused by IIa and IId subtypes. As most biological characterizations have been performed on IIa subtypes, the biological and genetic characteristics of IId subtypes in China are not clear. We evaluated the infection and genetic characteristics of IId isolates in interferon-γ-knockout mice using qPCR to quantify oocyst shedding, histological examination to monitor pathological changes and comparative genomic analyses to identify infectivity and virulence-associated differences. Compared with the reference IIa isolate, mice infected with the IId isolates had significantly higher and longer oocyst shedding and lower body weight gain. In addition, the four IId isolates examined differed significantly in infectivity (as indicated by the median infective dose), oocyst shedding duration, and pathogenicity. Comparative genomic analysis indicated that the IId isolates had three more subtelomeric genes than the reference IIa isolate and 5385-5548 nucleotide substitutions, with the hypervariable genes mostly in two blocks on chromosome 1. In contrast, the four IId isolates differed from each other by 77-1,452 nucleotides, with virulence-associated sequence differences mainly in nine genes within a 28-kb block on chromosome 6. These data indicate the newly emerged C. parvum IId subtypes in China have high animal infectivity and unique genomic characteristics.