Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR-insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

Objective To explore the association of (cardiometabolic index , CMI ) and ( lipid accumulation product , LAP ) with the prevalence of hypertension in adults in Pingshan District, Shenzhen, and to evaluate the predictive value of CMI and LAP for the prevalence of hypertension. Methods A cross-sectional survey was conducted, in which 1000 permanent residents aged 18-69 years in Pingshan District, Shenzhen were randomly selected as survey subjects. The data were collected using questionnaires, physical measurements and blood tests, and the relationship between CMI, LAP and hypertension prevalence was analyzed using logistic regression models. Results A total of 987 subjects were included in the analysis, including 471 (47.72%) males and 516 (52.28%) females, with an average age of 40.9 ± 11.1 years. Subjects of different genders were divided into groups Q1 to Q4 according to quartiles of CMI and LAP, and the prevalence of hypertension increased with increasing levels of CMI and LAP in both men and women (P for trend < 0.001). Logistic regression analysis revealed that after adjusting for variables such as age and occupation, the OR for hypertension was 1.251 (1.025-1.526) and 1.685 (1.001-2.836) for men and women, respectively, for each standard deviation increase in CMI; the OR for hypertension was 3.519 (1.343-9.222) for men in the Q4 group, compared to the CMI subgroup Q1. For each standard deviation increase in LAP, the ORs for hypertension were 1.355 (1.089-1.686) and 1.825 (1.023-3.254) for men and women, respectively; compared to LAP subgroup Q1, the ORs for hypertension in the male Q3 and Q4 groups were 2.554 (1.103-5.909) and 5.322 (2.393-11.834), while the OR for hypertension in the female Q4 group was 2.906 (1.096-7.703). ROC analysis revealed that the area under the curve (AUC) for CMI, LAP, and BMI was 0.671, 0.704, and 0.702 for males, and 0.660, 0.722, and 0.697 for females, respectively. The AUC for LAP was greater than that for CMI for different genders (P < 0.01). Conclusion The greater the CMI and LAP values in adults in Pingshan District, Shenzhen , the higher the prevalence of hypertension. CMI and LAP have certain values in predicting the prevalence of hypertension.

Objective : To investigate the effects of N-cadherin silencing on the proliferation and migration of human dental pulp stem cells (DPSCs) and to provide experimental evidence for DPSCs-based dental pulp regeneration. Methods: DPSCs were transfected with N-cadherin shRNA lentivirus, and the knockdown efficiency of N-cadherin at both the mRNA and protein levels was confirmed by qRT-PCR and Western blot. The experiment included a negative control group (shRNA -NC) and an N-cadherin shRNA silencing group. Cell proliferation was detected by the CCK-8 method. Cell cycle and apoptosis were assessed by flow cytometry, and cell migration was detected using the Transwell method. Results: N-cadherin shRNA significantly reduced the expression levels of N-cadherin mRNA and protein in DPSCs (P<0.001). The proliferation activity of the N-cadherin shRNA group was significantly greater than that of the shRNA-NC group on the 3rd and 4th days after cell inoculation and lower than that of the shRNA-NC group from the 6th to 8th days (P<0.05). On the 3rd day after cell inoculation, the proportion of cells in S phase and G2 phase in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.05). On the 6th day after cell inoculation, the proportion of cells in S phase and G2 phase in the N-cadherin shRNA group was lower than that in the shRNA-NC group (P<0.05), and the proportion of apoptotic cells in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.01). Low densities cells and high densities cells were inoculated into Transwell upper chamber for 20 h, the number of cells passing through the membrane pores of upper chamber in the N-cadherin shRNA group was greater than that in the shRNA-NC group (P<0.001). Conclusion Silencing N-cadherin expression can promote the early proliferation and migration of DPSCs.

Vital pulp therapy aims to maintain healthy pulp tissue as much as possible to improve the long-term survival of teeth. It has limited indications and uncertain curative effects. The pathological changes in inflamed pulp are the histological basis for the determination of treatment strategies and the treatment outcome; however, pulp sensitivity testing cannot reflect the actual histological status of the pulp. With the development of basic and clinical research on vital pulp therapy, the innovation of modern diagnostic and therapeutic technology and capping material, vital pulp therapy can be used as a treatment of teeth on which it was previously thought pulpectomy was necessary. Based on the evidence-based literature, this paper analyzes and summarizes the pathological changes of pulpitis and clinical research on the treatment of pulpitis. Vital pulp therapy can be a treatment for mature teeth with carious exposure and symptoms of irreversible pulpitis if comprehensive applications, including laser Doppler flowmetry, tissue oxygen monitoring, magnetic resonance imaging and microscopy, are used to determine the degree of pulp retention and if infection control and the use of biocompatible capping material are emphasized. In the future, it will be necessary to improve the success rate of vital pulp therapy for the treatment of pulpitis through research on the mechanism of pulp repair and regeneration, the precise diagnosis of pulpitis, and the development of pulp capping materials.

Objective: To analyze the epidemiological characteristics of hand foot and mouth disease (HFMD) cases caused by Coxsackie virus A16 (Cox A16) in Guangdong province from 2012 to 2016. Methods: The data of mild HFMD cases caused by Cox A16 were collected from 8 sentinel hospitals in 8 prefecture-level cities in Guangdong to estimate Cox A16 infection status and its population and time distribution characteristics. Results: (1) The highest estimated incidence of Cox A16 infection was in 2014 (113.0/100 000), followed by 2016 (86.4/100 000) and 2012 (79.1/100 000), while the estimated incidence was lower in 2015 (29.0/100 000) and 2013 (28.8/100 000). (2) Cox A16 was confirmed to be the predominant pathogen causing HFMD outbreaks (54.6%, 89/163). The number of outbreaks in the year with high incidence (28 outbreaks) was 11.2 times higher than that in the year with low incidence (2.5 outbreaks). (3) Across all age groups, the annual estimated incidence of Cox A16 infection decreased with age (trend χ(2)=853 905.63, P<0.01). The incidence was highest in age group 1 year (1 449.2/100 000), followed by that in age group 3 years (1 097.0/100 000), in age group 2 years (1 083.5/100 000), in age group 4 years (687.8/100 000) and in age group 0 year (604.9/100 000). Among the age groups <12 months, the estimated incidence increased with age (trend χ(2)=5 541.77, P<0.01), which was highest in age group 11-months (2 105.1/100 000), followed by that in age groups 10-months (1 448.6/100 000), 9-months (938.3/100 000), 8-months (703.3/100 000) and 6-months (664.6/100 000). (4) The annual incidence peak was during May (143.9/100 000)-June (131.5/100 000). Conclusion: The prevalence of Cox A16 infection differed with year in Guangdong during 2012-2016. When the incidence of Cox A16 infection was high, more outbreaks occurred. The prevalence occurred mainly in nurseries and kindergartens from May to June each year. Children aged 0-4 years were the high risk group for Cox A16 infection, children aged 6-11 months were at high risk for Cox A16 infection.
Animals ; Child ; Child, Preschool ; China/epidemiology* ; Cities ; Coxsackievirus Infections/epidemiology* ; Disease Outbreaks ; Enterovirus A, Human/isolation & purification* ; Hand, Foot and Mouth Disease/epidemiology* ; Hospitals ; Humans ; Incidence ; Infant ; Schools

Objective: To understand the epidemiologic characteristics of outbreaks, caused by norovirus-GⅡ.2、GⅡ.17 and GⅡ.4/Sydney in Guangdong Province from 2013 to 2017 and to provide scientific evidence for epidemic prevention and control. Methods: Incidence data of norovirus outbreaks in Guangdong from January 1(st) 2013 to November 30(th) 2017 were collected from Public Health Emergency Management Information System. RT-PCR was performed for every case of each outbreak to detect norovirus nucleic acid and gene sequencing was conducted to identify the genotype of norovirus. Characteristics of norovirus GⅡ.2, GⅡ.17 and GⅡ.4/Sydney outbreaks were analyzed. Directly standardized method was used to calculate the proportion of symtoms as diarrhea and vomitting. Results: From January 1(st) 2013 to November 30(th) 2017, a total of 167 norovirus outbreaks were reported in Guangdong, and 115 outbreaks were caused by norovirus GⅡ.2, GⅡ.17 and GⅡ.4/Sydney respectively. The outbreaks caused by norovirus GⅡ.2 accounted for 39.68% (25/63) in primary schools, 28.57% (18/63) in child care settings, 25.40% (16/63) in middle schools and 6.35% (4/63) in universities. Outbreaks caused by norovirus GⅡ.17 accounted for 41.03% (16/39) in middle schools, 20.51% (8/39) at workplaces, 15.38% (6/39) in primary schools, 12.82% (5/39) in universities, 5.13% (2/39) in communities and child care settings respectively. The outbreaks caused by norovirus GⅡ.4/Sydney accounted for 53.85% (7/13) in universities, 15.38% (2/13) in child care settings and at workplaces respectively, 7.69%(1/13) in primary schools and middle schools respectively. The outbreaks caused by norovirus GⅡ.2 had 77.78% (49/63) of contact transmission, 17.46% (11/63) of food-borne transmission. The outbreaks caused by norovirus GⅡ.17 showed 53.85% (21/39) of food-borne transmission, 15.38% (6/39) of contract transmission, 12.82% (5/39) of water-borne transmission. The outbreaks caused by norovirus GⅡ.4/Sydney had 53.85% (7/13) of food-borne transmission, 38.46% (5/13) of the contact transmission. In terms of the clinical manifestations, the standardized proportion of vomit was 73.76% and the proportion of diarrhea was 42.85% in cases infected with norovirus GⅡ.2, the proportion of standardized of vomit was 76.37% and the proportion of diarrhea was 51.40% in cases infected with norovirus GⅡ.17, with the standardized proportion of vomit was 54.10% and the proportion of diarrhea was 55.95% in cases infected with norovirus GⅡ.4/Sydney. Conclusions: The outbreaks caused by norovirus GⅡ.2 through contact transmission mainly occurred in primary schools, child care settings and middle schools. The outbreaks caused by norovirus GⅡ.17 through food-borne transmission mainly occurred in middle schools and at workplaces. The outbreaks caused by norovirus GⅡ.4/Sydney food-borne transmission and contact mainly occurred in universities.
Adolescent ; Caliciviridae Infections/epidemiology* ; Child ; Child, Preschool ; Diarrhea/etiology* ; Disease Outbreaks ; Epidemics ; Gastroenteritis/epidemiology* ; Genotype ; Humans ; Norovirus/isolation & purification* ; Reverse Transcriptase Polymerase Chain Reaction ; Sentinel Surveillance ; Vomiting/etiology*

OBJECTIVETo understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors.

METHODSWe recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model.

RESULTSIn individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001).

CONCLUSIONCDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.

Adiponectin ; blood ; Aged ; Brain Ischemia ; blood ; genetics ; Cadherins ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Stroke ; blood ; genetics

OBJECTIVETo compare the ettect and side-ettect of fluoxetine and combination of fluoxetine and Chinese or Tibetan medicine in treating senile depression in plateau district. Methods Ninety patients with diagnosis of senile depression conformed to CCMD-3 standard, in plateau district of 2260 - 3200 m altitude were randomly divided into three groups and treated with fluoxetine (group A), fluoxetine plus Sanpu Xinnao Xin granule (group B) and fluoxetine plus Xiaoyao pill (group C), respectively, 30 cases in each group. Therapeutic effects were evaluated with Hamilton' s depressive scale (HAMD) and treatment emergent symptom scale (TESS) after 6 weeks treatment.

RESULTSThere was no significant difference in the therapeutic effects between the three groups. The adverse reaction in Group B and C was less than that in Group A (P<0.01). Conclusion Sanpu Xinnao Xin granule and Xiaoyao pill can raise the tolerance of patients with senile depression in plateau area against the adverse reaction of fluoxetine.

Aged ; Altitude ; Antidepressive Agents, Second-Generation ; therapeutic use ; Depressive Disorder ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Fluoxetine ; therapeutic use ; Humans ; Middle Aged ; Phytotherapy ; Serotonin Uptake Inhibitors ; therapeutic use

OBJECTIVETo evaluate the safety, immunogenicity and fit dosage of Healive inactivated hepatitis A vaccine (HAV) in children.

METHODSA total of 85 susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled from two adjacent villages in a county. The volunteers were randomized allocated into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0 ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the same dose was given at 12th month. Local and systemic side effects were examined and seroconversion rate as well as geometric mean titers of anti-HAV antibody were tested at 3-week, 12-month after the primary dose and at 1 month after the booster dose.

RESULTSThe vaccine was well tolerated in both groups. At 21 days after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups respectively. At 12 months after the primary dose, the seroconversion rate of anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05) respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21 696 mIU/ml.

CONCLUSIONGMT of the 0, 12 month schedule was higher than other schedule after the booster vaccination. The Healive inactivated vaccine can be used for emergency vaccination. The Healive inactivated vaccine produced by Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose was considered appropriate for children.

Child ; Child, Preschool ; Dose-Response Relationship, Immunologic ; Drug Administration Schedule ; Hepatitis A ; immunology ; prevention & control ; Hepatitis A Antibodies ; analysis ; Hepatitis A Vaccines ; administration & dosage ; immunology ; Humans ; Vaccines, Inactivated ; administration & dosage ; immunology