Molecular characterization of physis tissue and hormonal profiles of female rats neonatally exposed to low-dose bisphenol A.

Physis is a complex cartilaginous structure that is critical for longitudinal bone growth. As one of the endocrine-disrupting chemicals, bisphenol A (BPA) can interfere with the physis by deranging the complex networks of nutritional, cellular, paracrine, and endocrine factors, and this affects longitudinal bone growth, leading to different growth outcomes. However, the exact mechanisms underlying these phenomena remain unclear. Therefore, understanding the molecular pathways involved in the physis after neonatal exposure to low-dose BPA may permit the identification of research targets for therapeutics, which may aid in modulating the process of growth plate closure. In the present study, female Sprague-Dawley rats were exposed to 0.05 mg·kg-1·day-1 of BPA and corn oil vehicle from postnatal day 1 (PND1) to 15 via subcutaneous injection. Next-generation RNA sequencing was performed for the mRNA isolated from the physis. The levels of osteocalcin (OC), growth hormone (GH), and insulin-like growth factor 1 (IGF-1) were measured on PND30 (BPA0.05mg vs. Vehicle; n = 5 for each group). We observed statistically significant enrichment of gene sets in the BPA0.05mg tissues compared with the Vehicle tissues. Further analysis of the differentially expressed genes (DEGs) identified BPA0.05mg-specific networks of secreted proteins (LEP, NPY, AGT, ACE2, C4B, and C4BPA) as well as those of local matrix and protease proteins (FBN2, LAMC2, ADAMTS16, and ADAMTS19). Furthermore, the levels of OC and GH were affected by BPA exposure. Our results revealed the specific molecular characteristics of physis contaminated with BPA and may provide new clues for physis maturation and supervision of industrial products and occupational exposure.

Long-term immune responses in patients with confirmed novel coronavirus disease-2019: a 9-month prospective cohort study in Shanghai, China.

BACKGROUND: The duration of antibodies against SARS-CoV-2 in Covid-19 patients remains uncertain. Longitudinal serological studies are needed to prevent disease and transmission of the virus. METHODS: In 2020, 414 blood samples were tested, obtained from 157 confirmed Covid-19 patients, in a prospective cohort study in Shanghai. RESULTS: The seropositive rate of IgM peaked at 40.5% (17/42) within 1 month after illness onset and then declined. The seropositive rate of IgG was 90.6% (58/64) after 2 months, remained above 85% from 2 to 9 months and was 90.9% (40/44) after 9 months. Generalized estimating equations models suggested that IgM (P < 0.001) but not IgG significantly decreased over time. Age ≥ 40 years (adjusted odds ratio [aOR] 4.531; 95% confidence interval [CI] 1.879-10.932), and cigarette smoking (aOR 0.344; 95% CI 0.124-0.951) were associated with IgG, and age ≥ 40 years (aOR 2.820; 95% CI 1.579-5.036) was associated with IgM. After seroconversion, over 90% and 75.1% of subjects were estimated to remain IgG-positive 220 and 254 days, respectively. Of 1420 self-reported symptoms questionnaires, only 5% reported symptoms 9 months after onset. CONCLUSIONS: In patients with a history of natural infection, anti-SARS-CoV-2 IgG is long-lived, being present for at least 9 months after illness onset. The long duration of natural immunity can mitigate and eliminate Covid-19 and the ongoing pandemic.

Epidemiological and clinical characteristics of 161 discharged cases with coronavirus disease 2019 in Shanghai, China.

BACKGROUND: In December 2019, the outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan, China, and rapidly spread to other regions. We aimed to further describe the epidemiological and clinical characteristics of discharged COVID-19 cases and evaluate the public health interventions. METHODS: We collected epidemiological and clinical data of all discharged COVID-19 cases as of 17 February 2020 in Shanghai. The key epidemiological distributions were estimated and outcomes were also compared between patients whose illness were before 24 January and those whose illness were after 24 January. RESULTS: Of 161 discharged COVID-19 cases, the median age was 45 years, and 80 (49.7%) cases were male. All of the cases were categorized as clinical moderate type. The most common initial symptoms were fever (85.7%), cough (41.0%), fatigue (19.3%), muscle ache (17.4%), sputum production (14.9%), and there were six asymptomatic cases. 39 (24.2%) cases got infected in Shanghai, and three of them were second-generation cases of Shanghai native cases. The estimated median of the time from onset to first medical visit, admission, disease confirmation, and discharge for 161 cases was 1.0 day (95% CI, 0.6-1.2), 2.0 days (95% CI, 1.5-2.6), 5.2 days (95% CI, 4.6-5.7), 18.1 days (95% CI, 17.4-18.8), respectively. The estimated median of the time from admission to discharge was 14.0 days (95% CI, 13.3-14.6). The time from onset to first medical visit, admission and disease confirmation were all shortened after the Shanghai's first-level public health emergency response. In Cox regression model, the significant independent covariates for the duration of hospitalization were age, the time from onset to admission and the first-level public health emergency response. CONCLUSIONS: Local transmission had occurred in Shanghai in late January 2020. The estimated median of the time from onset to discharge of moderate COVID-19 was 18.1 days in Shanghai. Time intervals from onset to first medical visit, admission and disease confirmation were all shortened after the Shanghai's first-level public health emergency response. Age, the first-level public health emergency response and the time from onset to admission were the impact factors for the duration of hospitalization.

Enhanced T-cell proliferation and IL-6 secretion mediated by overexpression of TRIM21 in oral lesions of patients with oral lichen planus.

BACKGROUNDS: To explore the expression and functions of the tripartite motif-containing protein 21 (TRIM21) in oral lichen planus(OLP) lesions. METHODS: Paraffin sections of buccal mucosa samples from 15 cases of reticular oral lichen planus (OLP) patients and 10 healthy controls were used for immunohistochemistry to determine expression and distribution of TRIM21. Buccal mucosae from 11 OLP patients and seven healthy controls were analyzed by qPCR to quantify its gene expression. Peripheral blood mononuclear cells and CD3+ cells from four pairs of age- and sex-matched OLP patients and healthy controls were isolated for immunocytochemistry and culture. Following lentivirus-mediated overexpression of TRIM21 gene in CD3+ cells, CCK-8 was applied to evaluate cell proliferation. Cytokines including IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, and IFN-γ in the supernatants were measured by the cytometric bead array and verified by ELISA. RESULTS: A larger number of TRIM21-positive cells infiltrating the lamina propria were observed in OLP lesions by immunohistochemistry than those of healthy controls. Significantly higher transcription of TRIM21 was revealed by qPCR. TRIM21 overexpression in CD3+ cells significantly enhanced the proliferation and IL-6 secretion in CD3+ cells from 12 to 72 hours. CONCLUSION: Overexpressed TRIM21 in OLP may be a primary proinflammatory molecule rather than a secondary and inducible regulatory factor in immunopathogenesis of OLP.

Three infection clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19), Shanghai, China, January to February 2020.

We report three clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19) between January and February 2020 in Shanghai, China. Investigators interviewed suspected COVID-19 cases to collect epidemiological information, including demographic characteristics, illness onset, hospital visits, close contacts, activities' trajectories between 14 days before illness onset and isolation, and exposure histories. Respiratory specimens of suspected cases were collected and tested for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The interval between the onset of illness in the primary case and the last contact of the secondary case with the primary case in our report was 1 to 7 days. In Cluster 1 (five cases), illness onset in the five secondary cases was 2 to 5 days after the last contact with the primary case. In Cluster 2 (five cases) and Cluster 3 (four cases), the illness onset in secondary cases occurred prior to or on the same day as the onset in the primary cases. The study provides empirical evidence for transmission of COVID-19 during the incubation period and indicates that pre-symptomatic person-to-person transmission can occur following sufficient exposure to confirmed COVID-19 cases. The potential pre-symptomatic person-to-person transmission puts forward higher requirements for prevention and control measures.

A Feed-Forward Regulatory Loop between HuR and the Long Noncoding RNA HOTAIR Promotes Head and Neck Squamous Cell Carcinoma Progression and Metastasis.

BACKGROUND/AIMS: The lncRNA Homeobox (HOX) transcript antisense RNA (HOTAIR) is overexpressed in numerous cancers. HuR is also overexpressed during tumourigenesis and is abnormally present within the cytoplasm, where it binds to AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally regulates the expression of its target genes. However, whether HOTAIR is regulated and the mechanisms by which it affects head and neck squamous cell carcinoma (HNSCC) are not well understood. METHODS: MTT, cell cycle arrest and apoptotic assays were used to examine the effects of HOTAIR and HuR on cell viability in SCC25 and FaDu cells. Wound healing and transwell invasion analysis were performed to detect the effects of HOTAIR and HuR on cell migration and invasion. The interaction between HuR and HOTAIR was confirmed via qRT-PCR, western blots, luciferase reporter and RIP assays. Finally, qRT-PCR analysis was used to detect the levels of HuR and HOTAIR in HNSCC tumours and adjacent normal tissues. RESULTS: Knockdown of HOTAIR and HuR decreased cell viability, cellular migration and invasion. Moreover, HuR interacted and stabilized HOTAIR stability and thus promoted HOTAIR expression. Notably, HOTAIR acted as a miRNA sponge for HuR. HuR also reinforced HOTAIR sponge activity through miRNA recruitment, thus enhancing HuR expression in turn. Finally, HuR and HOTAIR levels were positively correlated and significantly up-regulated in tumours samples. CONCLUSION: We demonstrated the existence of a regulatory loop in which the expression of HOTAIR and HuR is reciprocally and temporally regulated during the metastasis and progression of HNSCC.

Evolving Diversity of Hepatitis C Viruses in Yunnan Honghe, China.

The Chinese Honghe Autonomous Prefecture (Honghe) in Yunnan Province is a unique ethnic area because it is inhabited by more than ten different minority ethnic groups. Geographically, Honghe directly shares a border with Vietnam. The objective of this study was to investigate genetic diversity and distribution of the Hepatitis C virus (HCV) in Honghe. Ninety nine subjects who were infected with HCV or HCV/HIV (Human Immunodeficiency Virus Type 1) were recruited into this study. HCV genotypes and subtypes were determined based on the sequences of the core/envelope 1 (C/E1) and the nonstructural protein 5B (NS5B) genomic regions. The viral diversity and origins of dissemination were examined by phylogenetic analyses. Three HCV genotypes (1, 3 and 6) with six subtypes (1b, 3b, 3a, 6a, 6n and 6v) were identified. The most predominant form was genotype 3 (54.6%) followed by 6 (34.3%), and 1 (9.1%). The HCV subtype 3b appeared to be the most frequent form (38.4%) followed by 6n (20.2%) and 3a (16.2%). Statistical analyses suggested a possible rise of the genotype 6a in Honghe among intravenous drug users with HCV/HIV co-infections. Further phylogenetic analyses suggested that similar HCV-6a viruses might have been circulating in the Honghe area for more than a decade, which likely originated from Vietnam or vice versa. Two HCV samples with single HCV infection (SC34 and SC45) were isolated that could represent new recombinant variants. Although the genetic prevalence of HCV in Honghe is in general agreement with that of Southwest China and Yunnan Province, the diversity of HCV genotypes and subtypes in Honghe is somewhat unique and evolving. Information presented here should provide useful information for future health surveillance and prevention of HCV infection in this area.

Association of interleukin 12A gene polymorphisms with oral lichen planus in Chinese population.

BACKGROUND: Oral lichen planus (OLP) is a common autoimmune disorder with genetic and environmental factors contributing to its etiology. Interleukin (IL) 12 is a pro-inflammatory cytokine, which favors the differentiation of T helper 1 (Th1) cells, and forms a link between innate resistance and adaptive immunity. This study aimed to investigate the association between OLP susceptibility and clinical type in Chinese Han population with single-nucleotide polymorphisms (SNPs) of IL-12A gene. METHODS: Five SNPs of the IL-12A gene at positions rs2243115, rs2243123, rs583911, rs568408, and rs2243143 were performed in 292 patients with OLP and 686 healthy controls from East China. The five SNPs were genotyped by TaqMan PCR method. The genotype and allelic frequencies were calculated and analyzed. RESULTS: There was a significant difference in rs568408 genotype distributions between patients and controls (P = 0.043). Additionally, there were highly significant increases in rs568408 genotype distributions and allele A frequencies in the erosive OLP group as compared to the control group (P = 0.011, OR = 1.76, 95% CI: 1.133 -2.732). CONCLUSIONS: Our study indicated that the rs568408 variation in IL-12A gene could influence disease susceptibility, and was associated with the severity of OLP in our East Chinese cohort.

Maternal oral exposure to low-dose BPA accelerates the onset of puberty by promoting prepubertal Kiss1 expression in the AVPV nucleus of female offspring.

As the incidence of precocious puberty has risen in recent years and the age at puberty onset is younger, children may be at increased risk for health consequences associated with the early onset of puberty. Bisphenol A (BPA) is recognized as an endocrine disruptor chemical that is reported to induce precocious puberty. The effect of BPA exposure modes, times, and doses (especially low dose) were controversial. In the present study, we evaluated the potential effects of maternal exposure to low-dose BPA on the hypothalamus, particularly on the arcuate (ARC) nucleus and anteroventral periventricular (AVPV) nucleus during peri-puberty in offspring of BPA-treated rats. Pregnant rats were exposed to corn oil vehicle, 0.05 mg·kg-1·day-1 BPA, or 5 mg·kg-1·day-1 from gestation day 1 (GD1) to postnatal day 21 (PND21) by daily gavage. Body weight (BW), vaginal opening (VO), ovarian follicular luteinization, and relevant hormone concentrations were measured; hypothalamic Kiss1 and GnRH1 levels by western immunoblot analysis were also assessed as indices of puberty onset. During or after exposure, low-dose BPA restricted BW after birth (at PND1 and PND5), and subsequently accelerated puberty onset by promoting the expression of prepubertal Kiss1 and GnRH1 in the AVPV nucleus on PND30, leading to advanced VO, an elevation in LH and FSH concentrations (on PND30). We also noted increased BW on PND30 and PND35. Maternal oral exposure to low-dose BPA altered the BW curve during the neonatal and peripubertal periods, and subsequently accelerated puberty onset by promoting prepubertal Kiss1 expression in the AVPV nucleus.

Evaluating Seasonal Variations in Human Contact Patterns and Their Impact on the Transmission of Respiratory Infectious Diseases.

BACKGROUND: Human contact patterns are a key determinant driving the spread of respiratory infectious diseases. However, the relationship between contact patterns and seasonality as well as their possible association with the seasonality of respiratory diseases is yet to be clarified. METHODS: We investigated the association between temperature and human contact patterns using data collected through a cross-sectional diary-based contact survey in Shanghai, China, between December 24, 2017, and May 30, 2018. We then developed a compartmental model of influenza transmission informed by the derived seasonal trends in the number of contacts and validated it against A(H1N1)pdm09 influenza data collected in Shanghai during the same period. RESULTS: We identified a significant inverse relationship between the number of contacts and the seasonal temperature trend defined as a spline interpolation of temperature data (p = 0.003). We estimated an average of 16.4 (95% PrI: 15.1-17.5) contacts per day in December 2017 that increased to an average of 17.6 contacts (95% PrI: 16.5-19.3) in January 2018 and then declined to an average of 10.3 (95% PrI: 9.4-10.8) in May 2018. Estimates of influenza incidence obtained by the compartmental model comply with the observed epidemiological data. The reproduction number was estimated to increase from 1.24 (95% CI: 1.21-1.27) in December to a peak of 1.34 (95% CI: 1.31-1.37) in January. The estimated median infection attack rate at the end of the season was 27.4% (95% CI: 23.7-30.5%). CONCLUSIONS: Our findings support a relationship between temperature and contact patterns, which can contribute to deepen the understanding of the relationship between social interactions and the epidemiology of respiratory infectious diseases.

Relationship of close contact settings with transmission and infection during the SARS-CoV-2 Omicron BA.2 epidemic in Shanghai.

INTRODUCTION: We analysed case-contact clusters during the Omicron BA.2 epidemic in Shanghai to assess the risk of infection of contacts in different settings and to evaluate the effect of demographic factors on the association of infectivity and susceptibility to the Omicron variant. METHODS: Data on the settings and frequency of contact, demographic characteristics and comorbidities of index cases, contacts and secondary cases were analysed. Independent effect of multiple variables on the risk for transmission and infection was evaluated using generalised estimating equations. RESULTS: From 1 March to 1 June 2022, we identified 450 770 close contacts of 90 885 index cases. The risk for infection was greater for contacts in farmers' markets (fixed locations where farmers gather to sell products, adjusted OR (aOR): 3.62; 95% CI 2.87 to 4.55) and households (aOR: 2.68; 95% CI 2.15 to 3.35). Children (0-4 years) and elderly adults (60 years and above) had higher risk for infection and transmission. During the course of the epidemic, the risk for infection and transmission in different age groups initially increased, and then decreased on about 21 April (17th day of citywide home quarantine). Compared with medical workers (reference, aOR: 1.00), unemployed contacts (aOR: 1.77; 95% CI 1.53 to 2.04) and preschoolers (aOR: 1.61; 95% CI 1.26 to 2.05) had the highest risk for infection; delivery workers (aOR: 1.90, 95% CI 1.51 to 2.40) and public service workers (aOR: 1.85; 95% CI 1.64 to 2.10) had the highest risk for transmission. Contacts who had comorbidities (aOR: 1.10; 95% CI 1.09 to 1.12) had a higher risk for infection, particularly those with lung diseases or immune deficiency. CONCLUSION: Farmers' markets and households were the main setting for transmission of Omicron. Children, the elderly, delivery workers and public service workers had the highest risk for transmission and infection. These findings should be considered when implementing targeted interventions.

Effects of Endoscopic Sinus Surgery Combined with Budesonide Treatment on Nasal Cavity Function and Serum Inflammatory Factors in Patients with Chronic Sinusitis.

In this article, we have explored the effects of endoscopic sinus surgery together with budesonide treatment on nasal function and serum inflammatory factors on patients with chronic sinusitis. We retrospectively analyzed 120 patients with chronic sinusitis who were admitted to our hospital from March 2018 to March 2021 and were eligible for this study. They were separated into 2 groups according to different treatments, that is, the control group (treated with endoscopic surgery alone) of 58 cases and observation group (treated with endoscopic sinus surgery combined with budesonide) with 62 cases. Treatment efficacy, surgical status, overall symptom score before and after treatment, nasal mucociliary clearance function, serum eosinophils (EOS), serum immunoglobulin E (IgE), serum inflammatory factors, and occurrence of adverse reactions of both groups were recorded and compared. Total effective rate in the observation group presented strikingly more positive compared with that among patients in control group (P<0.05), as well as the data recorded in terms of operation time, blood loss during surgery and postoperative improvement time of patients (P<0.05). Overall symptom score, nasal mucociliary clearance, EOS, IgE and serum inflammatory factors in both groups were improved notably after treatment, while the observation group held a more obvious improvement. And it also had a markedly lower incidence of adverse reaction (P<0.05). Endoscopic sinus surgery combined with budesonide in the treatment of chronic sinusitis could effectively improve the clinical symptoms of patients, reestablish the function of the nasal cavity and improve their inflammation level. Meanwhile, it was of high safety and is worthy of clinical promotion.

Repair of exposure and fracture of the porous high-density polyethylene framework after ear reconstruction.

OBJECTIVE: To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction. STUDY DESIGN: A prospective case study. METHODS: From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient. RESULTS: After follow-up for 3-36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived. CONCLUSION: The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.

Development of a prognostic prediction model based on a combined multi-omics analysis of head and neck squamous cell carcinoma cell pyroptosis-related genes.

This study aimed to understand the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) and to develop and validate a prognostic model for HNSCC based on pyroptosis-associated genes (PAGs) in nasopharyngeal carcinoma. The Cancer Genome Atlas database was used to identify differentially expressed PAGs. These genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes functional annotation analyses and Gene Ontology analyses. The NLR family pyrin domain containing 1 (NLRP1) gene, charged multivesicular body protein 7 (CHMP7) gene, and cytochrome C (CYCS) gene were used to create a prognostic model for HNSCC. The results of the Kaplan-Meier (K-M) and Cox regression analyses indicated that the developed model served as an independent risk factor for HNSCC. According to the K-M analysis, the overall survival of high-risk patients was lower than that of low-risk patients. The hazard ratios corresponding to the risk scores determined using the multivariate and univariate Cox regression analyses were 1.646 (95% confidence interval (CI): 1.189-2.278) and 1.724 (95% CI: 1.294-2.298), respectively, and the area under the receiver operator characteristic curve was 0.621. The potential mechanisms associated with the functions of the identified genes were then identified, and the tumor microenvironment and levels of immune cell infiltration achieved were analyzed. The immune infiltration analysis revealed differences in the distribution of Th cells, tumor-infiltrating lymphocytes, regulatory T cells, follicular helper T cells, adipose-derived cells, interdigitating dendritic cells, CD8+ T cells, and B cells. However, validating bioinformatics analyses through biological experiments is still recommended. This study developed a prognostic model for HNSCC that included NLRP1, CHMP7, and CYCS.

Exploring the Mechanism of Yiqi Qingre Ziyin Method in Regulating Neuropeptide Expression for the Treatment of Atrophic Rhinitis.

Atrophic rhinitis (AR) is a chronic disease that causes severe structural changes to the nasal mucosa leading to squamous epithelial metaplasia. However, treatment regarding AR remains a major challenge. We used network pharmacology and molecular docking methods to explore the potential mechanisms of the Yiqi Qingre Ziyin method to modulate neuropeptides in the treatment of AR. The active ingredients of the Yiqi Qingre Ziyin method and their targets of action were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database Analysis Platform (TCMSP). Disease targets for AR were obtained from four databases: GeneCards, PharmGKB, DrugBank, and Online Mendelian Inheritance in Man (OMIM). A total of 59 active ingredients, 39 potential targets, and 76 relevant neuropeptides were obtained after deduplication. We constructed target interaction networks with the STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the 14 potential target proteins. We used Cytoscape software to construct the "drug-active ingredient-potential target" and "ingredient-target-pathway" networks of the Yiqi Qingre Ziyin method for treating AR. Molecular docking results suggest that dipeptidyl peptidase 4 (DPP4), opioid receptor gene d1 (OPRD1), and opioid receptor m1 (OPRM1) are key targets for the Yiqi Qingre Ziyin method. Therefore, this study proposed a potential mechanism for the treatment of AR by affecting the expression of neuropeptide-related genes (including DPP4, OPRD1, and OPRM1), which may potentially improve the immune microenvironment of the nasal mucosa.

Age-dependent and sex-dependent differences in mortality from influenza-associated cardiovascular diseases among older adults in Shanghai, China: a population-based study.

OBJECTIVES: Influenza epidemics lead to substantial morbidity and mortality among older adults. This study aimed to analyse and assess the age-specific and sex-specific differences in mortality rates for cardiovascular disease (CVD) associated with influenza in older adults. DESIGN: We obtained weekly data on mortality from CVD in adults≥60 years, categorised into five age groups. We used a quasi-Poisson model and adjusted for long-term and seasonal trends and absolute humidity as confounding factors. The male-to-female ratio (M/F ratio) was an indicator for assessing sex differences. SETTING: Shanghai, China. PARTICIPANT: We analysed 440 107 CVD deaths in adults aged ≥60 years, including 44 913 cases positive for influenza and 1 927 487 outpatient visits for influenza-like illness from 2010 to 2019. MAIN OUTCOME MEASURES: Age-specific and sex-specific excess CVD mortality rates in older adults for various combinations of CVDs and influenza viruses. RESULTS: Variations were observed in the excess mortality from CVD, ischaemic heart disease (IHD) and stroke depending on the influenza types/subtypes in different age and sex categories. The ≥85 years group had the highest excess mortality rates per 100 000 persons for CVD, IHD and stroke, while influenza A (H3N2) virus accounted for the highest mortality from CVD, IHD and stroke in people aged ≥65 years. Older men had a significantly lower influenza-associated IHD mortality rate than women, with an M/F ratio of 0.77 (p<0.05). CONCLUSIONS: Excess mortality rates for CVDs associated with influenza increased with age in older adults. The risk for influenza-associated IHD mortality was significantly higher in older women than men. Our findings will help implement targeted health strategies, including the promotion of influenza vaccination and early therapeutic intervention for the older population with CVD, to curb the influenza burden effectively.

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment.

Cognition may be improved by the active ingredients of the Yiqi Qingre Ziyin method in patients with atrophic rhinitis (AR). This study aimed to identify potential targets of the Yiqi Qingre Ziyin method for the treatment of patients with cognitive impairment. Nasal mucosal tissue samples from patients with AR were subjected to proteomic assays, and differentially expressed proteins were obtained. To explore the mechanism of AR leading to mild cognitive impairment (MCI), a differential analysis of AR related differential proteins in the MCI related GSE140831 dataset was performed. Most AR-related differential proteins are also differentially expressed in peripheral blood tissues of MCI, have similar biological functions and are enriched in similar pathways. These co-expressed differential factors in AR and MCI are known as common differential proteins of AR and MCI (CDPAM). Based on the analysis and validation of the random forest, support vector machine and neural network models, CDPAM acted as a diagnostic marker for MCI risk. Cytochrome C (CYCS) was significantly upregulated in the peripheral blood of patients with MCI. The active ingredients in the Yiqi Qingre Ziqin method were obtained and targeted 137 proteins. Among these targeted proteins, CYCS belong to the CDPAM set. Molecular docking and molecular dynamics analysis revealed that baicalein, an active ingredient in the Yiqi Qingre Ziyin method, stably targeted the CYCS protein. Results of the enrichment analysis revealed that the up-regulation of CYCS expression may have a defensive effect on the cells to resist foreign stimuli. Therefore, baicalein, an active ingredient in the Yiqi Qingre Ziyin method, may prevent the development and progression of MCI by targeting the CYCS protein.

An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes.

The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics.

Auricular reconstruction using Medpor combined with different hearing rehabilitation approaches for microtia.

BACKGROUND: Congenital microtia-atresia affects patients in two specific ways: severe conductive hearing loss and difficulty in integrating into social environments due to auricle malformation. AIMS/OBJECTIVES: To investigate the safety and efficacy of single-stage auricular reconstruction and hearing rehabilitation in children with microtia and external auditory canal atresia. MATERIAL AND METHODS: From January 2016 to December 2019, we included 32 patients with microtia and external canal atresia who received auricle reconstruction with high-density polyethylene (Medpor) framework and three different hearing rehabilitation approaches at the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Twenty patients underwent the traditional external auditory canal and middle ear repair (EACR), eight patients were implanted with Bonebridge (BB) devices, and four patients were implanted with bone-anchored hearing aid (BAHA) in one stage. Postoperative changes in auricle morphology and hearing and speech recognition and occurrence of complications were evaluated. RESULTS: After 6-24 months of follow-up, the auricle shape recovered well in all three groups, and the average score of 14 fine structures in the auricle was 9.43 (EACR), 10.67 (BB), and 9.75 (BAHA) points. The average score of auricle symmetry was 6.83 (EACR), 6.00 (BB), and 6.44 (BAHA) points. No significant differences in auricle shape were observed among the three groups (p > .05). After surgery, the average hearing improvement in the BB group was 43.33 dB, and the average speech recognition threshold declined to 42.28 dB. In the BAHA group, the average hearing improvement was 35 dB, and the average speech recognition threshold declined to 33.5 dB, similar to that of the BB group. However, in the EACR group, the average hearing improvement was only 4.13 dB, and the average speech recognition threshold declined to 11.36 dB. No vertigo, tinnitus, cerebrospinal fluid leakage, facial nerve paralysis, osseointegration failure, and other complications occurred in all the patients. In the EACR group, auricle stent fracture, ear canal restenosis, and canal atresia occurred in one patient each. In the BAHA group, two patients developed local ear infections. CONCLUSIONS AND SIGNIFICANCE: The procedure of single-stage auricular reconstruction and hearing rehabilitation for microtia is feasible and effective. The appropriate method of hearing reconstruction should be determined by evaluating the development of the inner and middle ear of the patients. For those patients with poor development of the mastoid and ossicular chain, hearing aid devices are recommended to achieve a stable and significant hearing effect.

Clusters of 2019 coronavirus disease (COVID-19) cases in Chinese tour groups.

International travel may facilitate the spread of the novel coronavirus disease (COVID-19). The study describes clusters of COVID-19 cases within Chinese tour groups travelling in Europe January 16-28. We compared characteristics of cases and non-cases to determine transmission dynamics. The index case travelled from Wuhan, China, to Europe on 16 January 2020, and to Shanghai, China, on 27 January 2020, within a tour group (group A). Tour groups with the same outbound flight (group B) or the same tourism venue (group D) and all Chinese passengers on the inbound flight (group C) were investigated. The outbreak involved 11 confirmed cases, 10 suspected cases and six tourists who remained healthy. Group A, involving seven confirmed cases and six suspected cases, consisted of familial transmission followed by propagative transmission. There was less pathogenicity with propagative transmission than with familial transmission. Disease was transmitted in shared outbound flights, shopping venues within Europe and inbound flight back to China. The novel coronavirus caused clustered cases of COVID-19 in tour groups. When tourism and travel opens up, governments will need to improve screening at airports and consider increased surveillance of tour groups-particularly those with older tour members.