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Influenza-like illness (ILI) varies in intensity year by year, generally keeping a stable pattern except for great changes of its epidemic pattern. Of the most impacting factors, urbanization has been suggested as shaping the intensity of influenza epidemics. Besides, growing evidence indicates the nonpharmaceutical interventions (NPIs) to severe acute respiratory syndrome coronavirus 2 offer great advantages in controlling infectious diseases. The present study aimed to evaluate the impact of urbanization and NPIs on the dynamic of ILI in Tongzhou, Beijing, during January 2013 to March 2021. ILI epidemiological surveillance data in Tongzhou district were obtained from Beijing Influenza Surveillance Network and separated into three periods of urbanization and four intervals of coronavirus disease 2019 pandemic. Standardized average incidence rates of ILI in each separate stages were calculated and compared by using Wilson method and time series model of seasonal ARIMA. Influenza seasonal outbreaks showed similar epidemic size and intensity before urbanization during 2013-2016. Increased ILI activity was found during the process of Tongzhou's urbanization during 2017-2019, with the rate difference of 2.48 (95% confidence interva [CI]: 2.44, 2.52) and the rate ratio of 1.75 (95% CI: 1.74, 1.76) of ILI incidence between preurbanization and urbanization periods. ILI activity abruptly decreased from the beginning of 2020 and kept at the bottom level almost in every epidemic interval. The top decrease in ILI activity by NPIs was shown in 5-14 years group in 2020-2021 influenza season, as 92.2% (95% CI: 78.3%, 95.2%). The results indicated that both urbanization and NPIs interrupted the epidemic pattern of ILI. We should pay more attention to public health when facing increasing population density, human contact, population mobility, and migration in the process of urbanization. NPIs and influenza vaccination should be implemented as necessary measures to protect people from common infectious diseases like ILI.

Air pollutants can cause serious harm to human health and a variety of respiratory diseases. This study aimed to explore the associations between air pollutants and outpatient visits for influenza-like illness (ILI) under urbanization process in the sub-center of Beijing. The data of ILI in sub-center of Beijing from April 1, 2014 to December 31, 2020 were obtained from Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and holidays. A total of 322,559 patients with ILI were included. The results showed that in the early urbanization period, the effects of PM

This work aimed to assess the role of TLR8 in cerebral I/R injury and its in-depth pathogenesis. Bioinformatics analysis indicated that TLR8 was up-regulated in patients with ischemic stroke than that in healthy control, and miR-18a-5p was the upstream regulatory of TLR8. Then, the rat pheochromocytoma PC12 cells were exposed in oxygen-glucose-deprivation/reoxygenation (OGD/R) conditions to construct a model in vitro. The functional experiments indicated that OGD/R can decline the viability and elevate the apoptosis of PC12 cells, while up-regulation of miR-18a-5p can alleviate OGD/R-induced cell injury. Notably, overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury. Finally, we found that up-regulation of miR-18a-5p obviously declined the protein levels of TLR4 and TLR7 as well as the phosphorylation of NF-κB, while overexpression of TLR8 canceled the decrease caused by miR-18a-5p up-regulation. In summing, our results illustrated that miR-18a-5p/TLR8 axis can mitigate OGD/R-induced cells injury through TLRs and NF-κB pathway. Overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury.

Hand, foot, and mouth disease (HFMD) is an infectious disease that usually occurs in children under 5 years and is caused by a group of enteroviruses. This study aimed to investigate the epidemiological characteristics of HFMD clusters from 2016 to 2020 in Tongzhou, Beijing, and explored the genetic evolution of CV-A6. The HFMD case information came from the Information System of China Center for Disease Control and Prevention (CDC), as well as the clusters information verification and on-site investigation by Tongzhou CDC. ARIMA model was applied to forecast HFMD clusters in 2020. Totally 440 HFMD clusters were reported during 2016-2020. The large peak of the clusters occurred in April-July, followed by a smaller peak in October-November during 2016-2019. However, in 2020, the two peaks disappeared. The main site of HFMD clusters was childcare facilities (65.0%) and mostly occurred in urban areas (46.1%). The detection rate of CV-A6 was the highest (36.1%), and cases with CV-A6 infection had the highest proportion of fever. The phylogenetic analysis based on CV-A6 VP1 gene showed that the predominant strains mainly located in Group F during 2016-2017, while changed into Group A during 2018-2020. HFMD clusters presented seasonality, mainly located in childcare facilities and urban areas, and CV-A6 was the major causative agent. Targeted prevention and control measures should be taken to reduce HFMD clusters.

BackgroundThe changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China.MethodFrom January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes.ResultA total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world.ConclusionsThe predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

Objective We reported an outbreak of human parainfluenza virus type 1 (HPIV1) in a kindergarten and explored the genetic characteristics of HPIV1 hemagglutinin-neuraminidase (HN) and fusion (F) genes to provide more evidence about HPIV1 outbreaks. Methods Suspected cases were the children with an influenza-like illness during June 20 to 26, 2018. Nasopharyngeal swabs were collected and screened to determine the presence of respiratory pathogens by real-time fluorescent quantitative polymerase chain reaction. The HN and F gene sequences of HPIV-positive samples were further amplified and sequenced to confirm the HPIV genotype and identify genetic characteristics. A phylogenetic tree, based on the HN and F genes, was reconstructed by maximum likelihood method. Results Fourteen children in the outbreak were diagnosed as upper respiratory tract infection. The most common symptom was cough (10/14), followed by rhinorrhea (5/14), sore throat (4/14), headache (1/14), and abdominal pain (1/14). Eight patients were positive for HPIV1 and negative for other pathogens. Phylogenetic tree demonstrated that the eight strains from the year 2018 in our study located in the clade 2.3. Two specific substitutions (N333S and I509M) in the amino acids of the F protein and two substitutions (V19A and L436I) in the HN protein were different from other strains in the clade 2. Conclusion HPIV1 was attributed to the outbreak, which may be related to the genetic variations of HPIV1.

BackgroundHerpangina is a highly infectious disease, which is usually prevalent in preschool children.MethodsThis study analyzed the clinical and pathogenic characteristics of herpangina children to demonstrate the epidemiology of herpangina. Clinical manifestations, laboratory indicators and pharyngeal swabs were collected from children with herpangina who were monitored by Tongzhou Center for Disease Control and Prevention in Beijing, 2008. Utilizing pharyngeal swabs, virus extraction and amplification were performed for nucleotide identification and sequencing. The phylogenetic analysis was conducted based on all sequences amplified in this study and strains retrieved from GenBank.ResultsAmong 190 children with herpangina, 69.0% (131/190) were positive for enterovirus. Eight genotypes were identified, mainly including CV-A6 (39/131), CV-A4 (25/131), CV-A10 (24/131). The phylogenetic analysis showed one CV-A6 strain of Tongzhou was imported from Japan. CV-A10 strains were clustered into five groups (A-E). The dominant cluster of CV-A10 was Group E6 between 2009 and 2013, and converted to Group E5 after 2013. CV-A6 was the predominant pathogen causing herpangina in Tongzhou in 2018, followed by CV-A4 and CV-A10.ConclusionsThe circulation of coxsackievirus had spatiotemporal cluster. In controlling the transmission of herpangina, the surveillance and reporting system should be enhanced.

Empirical analytic method and theoretical analytic method are usually applied to calculate and predict water gushing yield in the tunnel engineering in the past but have much limitations and errors. Ample water source, hydrodynamic conditions and expedite channels are essential for water-bursting accidents in railroad tunnel engineering. From a lot of study of fractal geometry in rock mass, it is found that the multi-dimension value of fissure network is colligate reflection of the length, the direction, space and the number of fissures, so the value can be used to describe the complicated frameworks in rock mass. But it is a sound tackle to quantities the complicated frameworks. Numerical simulating method is convinced to be applied to calculate and predict water gushing yield of tunnel and underground engineering. It focuses on analyzing texture characteristics of water-containing medium, building hydro-geological conceptual model, and modeling long-term hydrodynamic field development. An experimental application in Paoziling tunnel under-crossing mountain reservoirs in Hunan province was presented in this article, and long-term hydrodynamic field development had been obtained under the condition of drainage from the tunnel, and the gush yield in the tunnel during the process of storing water in the reservoir was also predicted.

Patients suffered from advanced endometrial cancer have poor prognosis. The five-year survival is only 25%. Histone deacetylase inhibitors have shown promise in the treatment for a variety of malignancies. In combination with traditional cytotoxic chemotherapy, histone deacetylase inhibitors can enhance the survival rate of cancer patients. This study was to investigate the effect and mechanism of trichostatin A (TSA), a histone deacetylase inhibitor, combined with paclitaxel (PTX) on the apoptosis of human endometrial carcinoma cell line Ark2.Ark2 cells were cultured in RPMI-1640 and treated with PTX alone, TSA alone or the two drugs in combination. Cell apoptosis was detected using Annexin V and Hoechst staining; perturbation of mitochondrial membrane potential was detected using MitoTracker red Poly (ADP-ribose) polymerase; caspase-9 degradation products and tubulin acetylation were detected by Western blot.Results of Annexin V showed that PTX (1.5 nmol/L) plus TSA (25 nmol/L) induced a significantly higher apoptotic rate (45.2%) than PTX alone (14.1%) or TSA alone (11.2%) did in Ark2 cells after drug treatment for three days. The results of Hoechst staining and Annexin V were consistent. A loss of mitochondrial membrane potential could activate the apoptotic cascade. Cleavages of PARP and caspase-9 were significantly apparent in PTX plus TSA group than in PTX group or TSA group (P0.05). PTX and TSA could induce tubulin acetylation. PTX in combination with TSA increased acetylated tublins and microtubule stability compared with either drug alone. The loss of mitochondrial membrane potential was more dramatic in the drug combination group than the single drug group. The effects of TSA and PTX were synergistic (q=2.54).TSA and PTX could induce apoptosis of Ark2 cells, which may be through the loss of mitochondrial membrane potential and acetylation of non-histone proteins induced by histone deacetylase inhibitors.