Outer membrane vesicles from genetically engineered Salmonella enterica serovar Typhimurium presenting Helicobacter pylori antigens UreB and CagA induce protection against Helicobacter pylori infection in mice.

Helicobacter pylori causes globally prevalent infections that are highly related to chronic gastritis and even development of gastric carcinomas. With the increase of antibiotic resistance, scientists have begun to search for better vaccine design strategies to eradicate H. pylori colonization. However, while current strategies prefer to formulate vaccines with a single H. pylori antigen, their potential has not yet been fully realized. Outer membrane vesicles (OMVs) are a potential platform since they could deliver multiple antigens. In this study, we engineered three crucial H. pylori antigen proteins (UreB, CagA, and VacA) onto the surface of OMVs derived from Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant strains using the hemoglobin protease (Hbp) autotransporter system. In various knockout strategies, we found that OMVs isolated from the ΔrfbP ΔfliC ΔfljB ΔompA mutants could cause distinct increases in immunoglobulin G (IgG) and A (IgA) levels and effectively trigger T helper 1- and 17-biased cellular immune responses, which perform a vital role in protecting against H. pylori. Next, OMVs derived from ΔrfbP ΔfliC ΔfljB ΔompA mutants were used as a vector to deliver different combinations of H. pylori antigens. The antibody and cytokine levels and challenge experiments in mice model indicated that co-delivering UreB and CagA could protect against H. pylori and antigen-specific T cell responses. In summary, OMVs derived from the S. Typhimurium ΔrfbP ΔfliC ΔfljB ΔompA mutant strain as the vector while importing H. pylori UreB and CagA as antigenic proteins using the Hbp autotransporter system would greatly benefit controlling H. pylori infection.

Outer membrane vesicles (OMVs), as a novel antigen delivery platform, has been used in vaccine design for various pathogens and even tumors. Salmonella enterica serovar Typhimurium (S. Typhimurium), as a bacterium that is easy to engineer and has both adjuvant efficacy and immune stimulation capacity, has become the preferred bacterial vector for purifying OMVs after Escherichia coli. This study focuses on the design of Helicobacter pylori ;(H. pylori) vaccines, utilizing genetically modified Salmonella OMVs to present several major antigens of H. pylori, including UreB, VacA and CagA. The optimal Salmonella OMV delivery vector and antigen combinations are screened and identified, providing new ideas for the development of H. pylori vaccines and an integrated antigen delivery platform for other difficult to develop vaccines for bacteria, viruses, and even tumors.

Epigallocatechin gallate alleviates non-alcoholic fatty liver disease through the inhibition of the expression and activity of Dipeptide kinase 4.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent glocal cause of chronic hepatic disease, with incidence rates that continue to rise steadily. Treatment options for affected patients are currently limited to dietary changes and exercise interventions, with no drugs having been licensed for the treatment of this disease. There is thus a pressing need for the development of novel therapeutic strategies. Work from our group suggests that the primary bioactive ingredient in green tea, epigallocatechin gallate (EGCG), may help reduce liver fat content and protect against hepatic injury through the inhibition of dipeptidyl peptidase 4 (DPP4) expression and activity. The study investigated the potential pathways by which EGCG may improve NAFLD, identified the sites of interaction between EGCG and DPP4, and proposed novel clinical treatment strategies. METHODS: A clinical randomized controlled trial was conducted to investigate the potential efficacy of EGCG in NAFLD patients. The study compared relevant indices before and after EGCG administration. Animal models of NAFLD were constructed using male C57BL/6J mice fed a high-fat diet to observe the ameliorative effects of EGCG on the livers of the model mice and to investigate the potential pathways by which EGCG alleviates NAFLD. The interaction mechanism between EGCG and DPP4 was investigated using oleic acid and palmitic acid-treated HepG2 cell lines. Plasmids in which different sites had been disrupted were used to identify the effective interaction sites. RESULTS: ECGC was found to suppress the accumulation of lipids, inhibit inflammation, remediate dysregulated lipid metabolism, and improve the pathogenesis of NAFLD via the inhibition of the expression and activity of DPP4. CONCLUSIONS: The study results indicate that EGCG has a positive impact on improving NAFLD. These results highlight promising new opportunities to safely and effectively treat NAFLD in the clinic. STUDY ID NUMBER: ChiCTR2300076741; https://www.chictr.org.cn/.

The effect of different treatment strategies on glycolipid metabolism disorders and cardiovascular events in primary aldosteronism.

Recent studies have explored the association between primary aldosteronism and cardiovascular disease incidence. The association between specific primary aldosteronism treatments and differential improvement in cardiovascular event rates is yet to be established. This study was designed to compare the relative effects of spironolactone therapy and surgical intervention on cardiovascular outcomes among primary aldosteronism patients. This retrospective observational study included 853 primary aldosteronism patients from the First Affiliated Hospital of China Medical University between 2014 and 2022. Patients who had completed abdominal computed tomography (CT) examinations with similar metabolic characteristics and 6-month follow-up analyses were included in this study. These patients were separated into a surgical treatment group (n = 33) and a spironolactone treatment group (n = 51). Demographic data, biochemical analysis results, liver/spleen (L/S) X-ray attenuation ratio, hospitalization frequency, and cardiovascular events were compared between the two groups. The spironolactone group demonstrated significantly improved metabolic characteristics compared to the surgical group, shown by lower BMI, blood pressure, total cholesterol (TC), insulin resistance index (IRI), and reduced non-alcoholic fatty liver disease prevalence. Metabolic parameters did not differ significantly within the surgical treatment group when comparing pre- and postoperative values. The incidence of cardiovascular events was lower in the spironolactone group compared to the surgery group (23/33 vs. 20/51, P < 0.001) despite higher hospitalization rates(37/31 vs. 61/53, P < 0.001). In patients with primary aldosteronism, spironolactone treatment is more effective than surgical intervention in remediating abnormal lipid and glucose metabolism while improving cardiovascular outcomes. Chinese clinical trial registry registration number: ChiCTR2300074574.

Boron-Doped Engineering for Carbon Quantum Dots-Based Memristors with Controllable Memristance Stability.

Carbon quantum dots-based memristors (CQDMs) have emerged as a rising star in data storage and computing. The key constraint to their commercialization is memristance variability, which mainly arises from the disordered conductive paths. Doping methodology can optimize electron and ion transport to help construct a stable conductive mode. Herein, based on boron (B)-doped engineering strategy, three kinds of comparable quantum dots are synthesized, including carbon quantum dots (CQDs), a series of boron-doped CQDs (BCQDs) with different B contents, and boron quantum dots. The corresponding device performances highlight the superiority of BCQDs-based memristors, exhibiting a ternary flash-type memory behavior with longer retention time and more controllable memristance stability. The comprehensive analysis results, including device performance, functional layer morphology, and material simulated calculation, illustrate that the doped B elements can directionally guide the migration of aluminum ions by enhancing the capture of free electrons, resulting in ordered conductive filaments and stable ternary memory behavior. Finally, the conceptual applications of logic display and logic gate are discussed, indicating a bright prospect for BCQDs-based memristors. This work proves that modest B doping can optimize memristance property, establishing a theoretical foundation and template scheme for developing effective and stable CQDMs.

Diabetes burden, trends, and inequalities in western pacific region, 1990-2019: A population-based study.

AIMS: The aim was to describe the diabetes regional burden, trends, and inequalities in the Western Pacific region. METHODS: The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates and average annual percentage changes (AAPCs) in diabetes in the Western Pacific region from 1990 to 2019. Cross-country inequalities in the DALY rates of diabetes were estimated between 1990 and 2019. RESULTS: The age-standardized incidence of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the Western Pacific region increased from 2.6 to 3.8 per 100,000 population (AAPC, 0.97 [95% CI 0.84 to 1.1]) and from 174.8 to 207.3 per 100,000 population (AAPC, 0.63 [95% CI 0.48 to 0.77]) between 1990 and 2019, respectively. The most substantial increase in the incidence of T1DM and T2DM was found in the groups aged 70 years and older (AAPC, 2.38 [95% CI 2.19 to 2.58]) and 15-49 years (AAPC, 1.58 [95% CI 1.43 to 1.72]) from 1990 to 2019, respectively. Age-standardized DALYs for T1DM decreased but those for T2DM increased between 1990 and 2019. The relative concentration index of DALYs in T1DM and T2DM changed from 0.11 in 1990 to -0.08 in 2019 and from 0.03 in 1990 to -0.04 in 2019, respectively. CONCLUSIONS: Over three decades, diabetes incidence in the Western Pacific region rose substantially, with inequalities among countries. The burden shifted from higher to lower sociodemographic index countries. Diabetes remains a public health challenge, especially among young populations. Urgent interventions for prevention and early detection are crucial.

Case report: A case of sepsis caused by rickettsial infection-induced hemophagocytic syndrome.

Hemophagocytic lymphohistiocytosis (HLH) is a rare histiocytic disorder characterized by reactive hyperplasia of the mononuclear phagocytic system, which is primarily caused by dysfunction of cytotoxic killer cells and natural killer cells, leading to antigen clearance barriers and the overactivation of the mononuclear phagocytic system due to continuous antigen stimulation. HLH encompasses a group of clinical syndromes marked by the overproduction of inflammatory cytokines. A 68-year-old Chinese man presented with persistent fever, chills, nausea, and vomiting; the patient had no history of any underlying conditions. Laboratory investigations revealed decreased levels of red blood cells, white blood cells, and platelets, along with reduced natural killer cell activity, increased CD25, hyperferritinemia, and the detection of Rickettsia DNA in his blood, meeting the diagnostic criteria of the Histiocyte Society HLH-2004 guidelines. The patient was treated with antibiotics, improving anemia, glucocorticoid therapy, and continuous renal replacement therapy (CRRT), temporarily improving his condition. However, the patient died after 2 years from chronic renal failure caused by septic shock.

Epidemiology of hand, foot and mouth disease and genomic surveillance of coxsackievirus A10 circulating in Zhejiang Province, China during 2017 to 2022.

BACKGROUND: Coxsackievirus A10 (CA10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD). OBJECTIVES: We aimed to perform a retrospective analysis of the molecular epidemiological characteristics and genetic features of HFMD associated with CA10 infections in Zhejiang Province from 2017 to 2022. STUDY DESIGN: Epidemiologic features were summarized. Throat swab specimens were collected and tested. The VP1 regions were sequenced for genotyping. CA10 positive samples were isolated. Whole genomes of CA10 isolations were sequenced. Nucleotide and amino acid changes were characterized. Phylogenetic trees were constructed. RESULTS: The number of HFMD cases fluctuated from 2017 to 2022. Children aged below 3 years accounted for the majority (66.29%) and boys were more frequently affected than girls. Cases peaked in June. The positivity rate of HEV was 62.69%. A total of 90 strains of CA10 were isolated and 53 genomes were obtained. All CA10 in this study could be assigned to two genogroups, C (C2) and F (F1 and F3). CONCLUSION: The clinical manifestations of HFMD associated with HEV are complex and diverse. CA10 infection may be emerging as a new and major cause of HFMD because an upward trend was observed in the proportion of CA10 cases after the use of EV71 vaccines. Different genogroups of CA10 had different geographic distribution patterns. Surveillance should be strengthened and further comprehensive studies should be continued to provide a scientific basis for HFMD prevention and control.

Visual analysis of global air pollution impact research: a bibliometric review (1996-2022).

The impact of air pollution is one of the hotspots attracting continuous scholarly attention, but the comprehensive statistical and visual analysis reviews are few. Employing the method of bibliometric analysis, this paper took the relevant literature from 1996 to April 2022 on the Web of Science as the research object. Through the methods of keyword co-occurrence analysis and burst analysis, the spatiotemporal evolution trend, cooperation network, outstanding scholars, knowledge base, and research focus of air pollution impact research are visually presented. Via constructing a common word matrix of high-frequency words, clustering analysis is used to aggregate high-frequency keywords into 24 clusters. By the strategic coordinate analysis method, the relationships within and between clusters were revealed. The main findings include (1) research on the impact of air pollution mainly focusing on human health; (2) the six keywords with the highest centrality are California, hydrocarbons, dioxide, generation, Asia, and diesel; (3) these 11 clusters may be developed into future research hotspots: particulate matter, nitrogen oxides, mortality, ozone, pollution, air quality, asthma, children, epidemiology, aerosols, and polycyclic aromatic hydrocarbons; and (4) seven topics are research hot: daily mortality, long-term exposure, coronary heart disease, concentration, North China plain, traffic-related air pollution, and air pollution.

Different Responses of Growing Season Ecosystem CO2 Fluxes to Rain Addition in a Desert Ecosystem.

Desert ecosystem CO2 exchange may play an important role in global carbon cycling. However, it is still not clear how the CO2 fluxes of shrub-dominated desert ecosystems respond to precipitation changes. We performed a 10-year long-term rain addition experiment in a Nitraria tangutorum desert ecosystem in northwestern China. In the growing seasons of 2016 and 2017, with three rain addition treatments (natural precipitation +0%, +50%, and +100% of annual average precipitation), gross ecosystem photosynthesis (GEP), ecosystem respiration (ER), and net ecosystem CO2 exchange (NEE) were measured. The GEP responded nonlinearly and the ER linearly to rain addition. The NEE presented a nonlinear response along the rain addition gradient, with a saturation threshold by rain addition between +50% and +100%. The growing season mean NEE ranged from -2.25 to -5.38 µmol CO2 m-2 s-1, showing net CO2 uptake effect, with significant enhancement (more negative) under the rain addition treatments. Although natural rainfall fluctuated greatly in the growing seasons of 2016 and 2017, reaching 134.8% and 44.0% of the historical average, the NEE values remained stable. Our findings highlight that growing season CO2 sequestration in desert ecosystems will increase against the background of increasing precipitation levels. The different responses of GEP and ER of desert ecosystems under changing precipitation regimes should be considered in global change models.

QCR7 affects the virulence of Candida albicans and the uptake of multiple carbon sources present in different host niches.

Background: Candida albicans is a commensal yeast that may cause life-threatening infections. Studies have shown that the cytochrome b-c1 complex subunit 7 gene (QCR7) of C. albicans encodes a protein that forms a component of the mitochondrial electron transport chain complex III, making it an important target for studying the virulence of this yeast. However, to the best of our knowledge, the functions of QCR7 have not yet been characterized. Methods: A QCR7 knockout strain was constructed using SN152, and BALb/c mice were used as model animals to determine the role of QCR7 in the virulence of C. albicans. Subsequently, the effects of QCR7 on mitochondrial functions and use of carbon sources were investigated. Next, its mutant biofilm formation and hyphal growth maintenance were compared with those of the wild type. Furthermore, the transcriptome of the qcr7Δ/Δ mutant was compared with that of the WT strain to explore pathogenic mechanisms. Results: Defective QCR7 reduced recruitment of inflammatory cells and attenuated the virulence of C. albicans infection in vivo. Furthermore, the mutant influenced the use of multiple alternative carbon sources that exist in several host niches (GlcNAc, lactic acid, and amino acid, etc.). Moreover, it led to mitochondrial dysfunction. Furthermore, the QCR7 knockout strain showed defects in biofilm formation or the maintenance of filamentous growth. The overexpression of cell-surface-associated genes (HWP1, YWP1, XOG1, and SAP6) can restore defective virulence phenotypes and the carbon-source utilization of qcr7Δ/Δ. Conclusion: This study provides new insights into the mitochondria-based metabolism of C. albicans, accounting for its virulence and the use of variable carbon sources that promote C. albicans to colonize host niches.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.

Epidemiological characteristics of influenza outbreaks in Zhejiang Province from 2013 to 2022 / 预防医学

Objective@#To investigate the epidemiological characteristics of influenza outbreaks in Zhejiang Province from 2013 to 2022, so as to provide insights into influenza prevention and control. @*Methods@#Data pertaining to influenza outbreaks reported in Zhejiang Province from 2013 to 2022 were collected from National Influenza Surveillance System in China, including time, region, cases and pathogen types of influenza outbreaks. The temporal, spatial and pathogen distribution of influenza outbreaks were analyzed using a descriptive epidemiological method. @*Results@#A total of 577 influenza outbreaks involving 448 698 individuals were reported in Zhejiang Province from 2013 to 2022, and the overall attack rate was 5.34% (23 974 cases), with no death reported. The lowest attack rate of influenza was 0.26%, and the highest was 80.00%, with a median attack rate of 10.89% (interquartile range, 24.26%). The outbreak had the shortest duration of 1.00 day, and the longest duration of 59.00 days, with a median duration of 9.00 (interquartile range, 11.00) days. There were 387 influenza outbreaks that occurred between November and January of the following year (67.07%), and the three highest numbers of outbreaks were reported in Hangzhou City (310 outbreaks), Wenzhou City (51 outbreaks) and Jinhua City (46 outbreaks). There were 395 outbreaks reported in urban regions (68.46%), 93 in counties and townships (16.12%) and 89 in rural regions (15.42%), and influenza outbreaks predominantly occurred in primary schools (487 outbreaks, 84.40%). In addition, the types of pathogens were alternately prevalent, with influenza B virus (241 outbreaks, 41.77%) and A/H3N2 virus (232 outbreaks, 40.21%) as predominant subtypes. @* Conclusions@#Influenza outbreaks mainly occurred in winter in Zhejiang Province from 2013 to 2022, and primary schools were main places of influenza outbreaks, while influenza B virus and A/H3N2 virus were predominant subtypes. It is necessary to reinforce the surveillance and report of influenza-like illness in schools and improve the coverage of influenza vaccination to prevent influenza outbreaks.

Association of Barrett's esophagus with obstructive sleep apnea syndrome: a bidirectional analysis of Mendelian randomization.

Background: Observational studies have reported associations between Barrett's esophagus (BE) and obstructive sleep apnea syndrome (OSAS), but the causal relationship remained unclear due to potential confounding biases. Our study aimed to elucidate this causal relationship by deploying a two-sample Mendelian randomization (MR) methodology. Methods: Instrumental variables (IVs) for Barrett's esophagus were obtained from a public database that comprised 13,358 cases and 43,071 controls. To investigate OSAS, we utilized summary statistics from a comprehensive genome-wide association study (GWAS) encompassing 38,998 cases of OSAS and 336,659 controls. Our MR analyses adopted multiple techniques, including inverse variance weighted (IVW), weighted median, weighted mode, MR-Egger, and simple mode. Results: The IVW analysis established a causal relationship between Barrett's esophagus and OSAS, with an odds ratio (OR) of 1.19 and a 95% confidence interval (CI) of 1.11-1.28 (p = 8.88E-07). Furthermore, OSAS was identified as a contributing factor to the onset of Barrett's esophagus, with an OR of 1.44 and a 95% CI of 1.33-1.57 (p = 7.74E-19). Notably, the MR-Egger intercept test found no evidence of directional pleiotropy (p > 0.05). Conclusion: This study identifies a potential association between BE and an increased occurrence of OSAS, as well as the reverse relationship. These insights could influence future screening protocols and prevention strategies for both conditions.

Resistance to thyroid hormone beta coexisting with papillary thyroid carcinoma-two case reports of a thyroid hormone receptor beta gene mutation and a literature review.

Resistance to thyroid hormone beta (RTHß) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features, which are caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies have indicated a close association between THRB mutations and human cancers, but the mechanistic role of THRB mutations in carcinogenesis is unknown. Herein, we report two cases of RTHß coexisting with papillary thyroid carcinoma (PTC) and their follow-up results. Two female patients presented with elevated serum thyroid hormone levels and nonsuppressed thyrotropin (TSH). Genetic analysis showed that each patient had a THRB gene mutation (p.P453T and p. R320H). Based on the results of ultrasound-guided fine-needle aspiration biopsy, the thyroid nodules were suspected to be PTC. Intraoperative pathology confirmed that the two patients had PTC with multifocal carcinoma of both lobes. One patient underwent total thyroidectomy and central lymph node dissection, and the other underwent total thyroidectomy alone. Following surgery, large doses of levothyroxine were administered to suppress TSH levels and prevent recurrent or persistent disease. However, it is difficult to continually suppress TSH levels below the upper limit of the normal range. To date, the two patients have experienced no recurrence of PTC on ultrasound.

Analysis of Galangin and Its In Vitro/In Vivo Metabolites via Ultra-High-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry.

Galangin, a naturally available flavonoid, induces a variety of pharmacological activities and biological effects via several mechanisms. However, in vivo metabolism of galangin has not been fully explored, which means knowledge of its pharmacodynamics and application potential is limited. The objective of this study was to establish an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method for the rapid profiling and identification of galangin metabolites in vitro and in vivo using unique online information-dependent acquisition with multiple mass defect filtering combined with dynamic background subtraction in positive ion mode. A total of 27 metabolites were detected and characterized, among which eight metabolites in liver microsomes and four metabolites in intestinal microflora were characterized, and 27 metabolites from rat plasma, bile, urine, feces, and a number of different tissue samples were characterized. Thirteen major metabolic pathways including hydrogenation, hydroxylation, glycosylation, methylation, acetylation, glucuronidation, and sulfation were observed to be attributable to the biotransformation of the metabolites. This study provides evidence for the presence of in vitro and in vivo metabolites and the pharmacokinetic mechanism of galangin. Moreover, the study promotes the further development and utilization of galangin and the plant from which it is derived, Alpinia officinarum Hance.

Seasonality and Meteorological Factors Associated With Different Hand, Foot, and Mouth Disease: Serotype-Specific Analysis From 2010 to 2018 in Zhejiang Province, China.

Background: Hand-foot-mouth disease (HFMD) is caused by a group of enteroviruses (EVs) and has a high incidence in children; some subtypes had high mortalities in children. The subtypes of HFMD had a different incidence across seasons. Thereby, we suspect that the infection of HFMD is varied by meteorological factors. However, studies examining serotype-specific associations between meteorological factors and HFMD incidence were rare. Methods: We obtained all HFMD cases that occurred from 1 January 2010 to 31 December 2018 in Zhejiang province from the China Information System for Disease Control and Prevention (CISDCP). Daily meteorological data for Zhejiang province were provided by the China Methodological Data Sharing Service System and linked to HFMD cases based on residential addresses and dates of onset. The associations between meteorological factors and HFMDs were examined using distributed lag non-linear models (DLNMs) for each serotype. Results: Overall, the incidences of all HFMD cases were increasing in study years, while the number of severe and fatality cases were decreasing. The dominant serotypes varied by study year. The association between temperature and incidence of both CVA16 and EV71 serotypes showed an inverted U shape. The risk ratio for CVA16 was increasing when temperature is 11-25°C, reaching the maximum RR at 18°C and humidity above 77% can promote the occurrence with CVA16, and temperature between 11 and 32°C with the maximum RR at 21°C and relative humidity above 77% are risk conditions of the occurrence of HFMD associated with EV71. For other enteroviruses causing HFMD, temperature above 11°C and humidity above 76% have a risk effect. CVA16, EV71, and all enteroviruses of HFMD have a maximum effect on lag day 0, and temperature is 35, 34, and 33°C respectively, while the enteroviruses of HFMD other than EV71 and CVA16 has a maximum effect when the temperature is 33°C and the lag time is 7 days. Conclusion: This study shows that meteorological factors have an effect on the occurrence of different HFMD serotypes. Local control strategies for public health should be taken in time to prevent and reduce the risk of HFMD while the weather is getting warmer and wetter.

The role of primary physician training in improving regional standardized management of diabetes: a pre-post intervention study.

BACKGROUND: Hierarchical diagnosis and treatment has been gradually implemented throughout the China. Primary physicians are the main force in primary-level medical and health services, which means that standardized training of primary-level doctors is indispensable. OBJECTIVES: Evaluation of the effect of primary physician training on standardized management of diabetes, and comparison of the effects of different training models. METHOD: The study selected 24 community health service centers from 4 cities in Liaoning Province, and consisted of two groups: primary physicians (n = 2083) who received training; and patients with diabetes (n = 585) in community health service centers. Short-term training effects on primary physicians were assessed through diabetes knowledge tests at baseline and at the end of training; the long-term effects of training on patients with diabetes were assessed by questionnaires at baseline and 1 year after training. The differences in training effects between different training models were compared. Complication screening results were also assessed. RESULTS: After training, the primary physicians' knowledge of diabetes diagnosis and treatment improved (p < 0.05). The complication screening rate of local diabetes patients increased from 22.2% before training to 27.7% 1 year after training (p = 0.033). There were significant differences in the training effect between different training models (p = 0.038). The short-term intensive training group demonstrated the greatest training effect, primary physicians under this training model are more likely to conduct standardized screenings for patients (OR = 1.806, 95%CI 1.008-3.233), and the complication screening rate was the highest (37.6%). CONCLUSION: This study shows that training of primary physicians is an effective way to improve the standardized management of diabetes, by improving the ability of primary physicians to manage diabetes in a standardized manner, so that patients in primary hospitals receive more comprehensive diagnosis and treatment services. Compared with scattered training throughout the year, short-term intensive training was found to be more effective.

Detection of Carbapenem Resistance of Proteus mirabilis Strains Isolated from Foxes, Raccoons and Minks in China.

Proteus mirabilis, an opportunistic pathogen, is found to be an emerging threat to both animals and humans for a variety of infections. However, the characteristics of P. mirabilis infections from foxes, raccoons and minks remain unclear. In this context, we identified the antibiotic resistance genes and virulence genes of P. mirabilis isolates from foxes, raccoons and minks in China. Most isolates showed resistance to florfenicol (90.57%), trimethoprim-sulfamethoxazole (73.58%), and imipenem (71.70%). A total of 73.58% of isolates were resistant to antibiotics from at least three or more classes, and were categorized as multi-drug resistant. A total of 33.33% of the isolates were resistant to antibiotics from seven classes. The most prevalent resistant were sul1 (94.34%), followed by floR, blaTEM, aac(6')Ib-cr and blaOXA-1 with the detection rate of 88.68%, 83.02%, 71.70% and 60.38%, respectively. Among the 51 P. mirabilis isolates that were resistant to beta-lactam antibiotics, all isolates carried at least one beta-lactam gene. In addition, blaNDM and blaOXA-24 genes were firstly reported in carbapenem-resistant P. mirabilis isolates from foxes, raccoons and minks. All isolates exhibited the virulence genes ureC, zapA, pmfA, atfA and mrpA. P. mirabilis isolates carrying all detected 10 virulence genes from different animal species showed different lethal abilities in a G. mellonella larvae model. More importantly, the profiles of antibiotic resistance genes of isolates from fur animals and the environment were generally similar, and phylogenetic analysis showed that the P. mirabilis isolates from farm environment samples may have close relatedness with that from animals.

Secular incidence trends and effect of population aging on mortality due to type 1 and type 2 diabetes mellitus in China from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

INTRODUCTION: Diabetes and population aging have become public health issues of global concern. The secular incidence trends and the impact of population aging on mortality due to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in China remain unclear. RESEARCH DESIGN AND METHODS: The incidence and mortality rates of T1DM and T2DM from 1990 to 2019 were abstracted from the Global Burden of Disease Study (GBD) 2019 database. Joinpoint regression and age-period-cohort models were used to calculate the average annual percentage change and relative risk (RR), respectively. A decomposition method was used to attribute changes in total deaths to population growth, population aging, and the mortality rate change from 1990 to 2019. RESULTS: From 1990 to 2019, the T1DM age-standardized incidence rate (ASIR) increased by 2.01% (95% CI 1.78% to 2.23%) in males and 1.70% (1.61% to 1.80%) in females, and the T1DM age-standardized mortality rate (ASMR) decreased by 1.96% (-2.22% to -1.71%) in males and 4.02% (-4.48% to -3.57%) in females. The T2DM ASIR increased by 0.81% (0.62% to 0.99%) in males and 0.37% (0.16% to 0.58%) in females, and the T2DM ASMR increased by 1.06% (0.87% to 1.25%) in males and decreased by 0.24% (-0.54% to 0.07%) in females. Compared with 1990, the proportions of deaths attributed to population aging ranged from 18.85% (T1DM) to 148.21% (T2DM) for males and 29.80% (T1DM) to 118.82% (T2DM) for females in 2019. CONCLUSIONS: The T1DM and T2DM incidence rates continually increased in China, particularly among young individuals. T1DM-related mortality decreased, while T2DM-related mortality increased in males. Population aging might be associated with a substantial change in the number of deaths from 1990 to 2019. To address the increase in T2DM-related deaths due to population aging, policymakers should promote aging-related health research and implement proven, cost-effective T2DM interventions.

Effects of the Simulated Enhancement of Precipitation on the Phenology of Nitraria tangutorum under Extremely Dry and Wet Years.

Plant phenology is the most sensitive biological indicator that responds to climate change. Many climate models predict that extreme precipitation events will occur frequently in the arid areas of northwest China in the future, with an increase in the quantity and unpredictability of rain. Future changes in precipitation will inevitably have a profound impact on plant phenology in arid areas. A recent study has shown that after the simulated enhancement of precipitation, the end time of the leaf unfolding period of Nitraria tangutorum advanced, and the end time of leaf senescence was delayed. Under extreme climatic conditions, such as extremely dry or wet years, it is unclear whether the influence of the simulated enhancement of precipitation on the phenology of N. tangutorum remains stable. To solve this problem, this study systematically analyzed the effects of the simulated enhancement of precipitation on the start, end and duration of four phenological events of N. tangutorum, including leaf budding, leaf unfolding, leaf senescence and leaf fall under extremely dry and wet conditions. The aim of this study was to clarify the similarities and differences of the effects of the simulated enhancement of precipitation on the start, end and duration of each phenological period of N. tangutorum in an extremely dry and an extremely wet year to reveal the regulatory effect of extremely dry and excessive amounts of precipitation on the phenology of N. tangutorum. (1) After the simulated enhancement of precipitation, the start and end times of the spring phenology (leaf budding and leaf unfolding) of N. tangutorum advanced during an extremely dry and an extremely wet year, but the duration of phenology was shortened during an extremely wet year and prolonged during an extremely drought-stricken year. The amplitude of variation increased with the increase in simulated precipitation. (2) After the simulated enhancement of precipitation, the start and end times of the phenology (leaf senescence and leaf fall) of N. tangutorum during the autumn advanced in an extremely wet year but was delayed during an extremely dry year, and the duration of phenology was prolonged in both extremely dry and wet years. The amplitude of variation increased with the increase in simulated precipitation. (3) The regulation mechanism of extremely dry or wet years on the spring phenology of N. tangutorum lay in the different degree of influence on the start and end times of leaf budding and leaf unfolding. However, the regulation mechanism of extremely dry or wet years on the autumn phenology of N. tangutorum lay in different reasons. Water stress caused by excessive water forced N. tangutorum to start its leaf senescence early during an extremely wet year. In contrast, the alleviation of drought stress after watering during the senescence of N. tangutorum caused a delay in the autumn phenology during an extremely dry year.