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Kaidian Chen,1,* Yao Lin,1,* Yuchun Liu,1,* Shuanglin Liao,2 Ruoxuan Yang,1 Jiefeng Huang,1 Mingwei Xu,1 Junbing He1 1The Intensive Care Unit, Jieyang Affiliated Hospital, Sun Yat-sen University, Jieyang, Guangdong, People’s Republic of China; 2The Intensive Care Unit, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junbing He; Mingwei XuThe Intensive Care Unit, Jieyang Affiliated Hospital, Sun Yat-sen University, Tianfu Road 107, Rongcheng district, Jieyang, 522000, Guangdong Province, People’s Republic of ChinaEmail junbinghe_gmc@163.com; mingweixu_gmc@126.comBackground: Complement 5 (C5) and C5a production play a pivotal role in the pathophysiology of sepsis. Strong evidence demonstrates an association of C5 gene polymorphisms with various inflammatory diseases. However, no current studies have explored the clinical relevance of C5 polymorphisms in sepsis.Methods: Two C5 gene polymorphisms, rs17611 and rs2269067, were identified by genotyping in 636 sepsis patients and 753 controls in a Han Chinese population. C5 gene expression was detected via quantitative real-time PCR. C5a and proinflammatory cytokine production was measured by enzyme-linked immunosorbent assay. An Annexin V apoptosis assay was performed to assess cell apoptosis.Results: Our results showed significantly lower frequencies of rs2269067 GC/CC genotypes or C allele in sepsis patients than healthy controls. The frequencies of rs17611 CC/CT genotypes or C allele were significantly overrepresented in both the septic shock and non-survivor subgroups. Patients with this sepsis-associated high-risk rs17611 C allele exhibited a significant increase in C5a, TNF-α and IL-6 production. However, no significant difference in C5a and downstream proinflammatory cytokine production was observed among patients with different rs2269067 genotypes. In addition, in vitro experiments showed an effect of recombinant C5a on enhancing LPS-stimulated IL-1β, IL-6 and TNF-α production and cell apoptosis in THP-1 monocytes.Conclusion: The rs2269067 polymorphism conferred protection against sepsis susceptibility. The rs17611 polymorphism was associated with increased C5a production, which ultimately potentiated the secretion of downstream proinflammatory cytokines and conferred susceptibility to sepsis progression and poor prognosis.Keywords: C5, C5a, polymorphism, sepsis, inflammation

Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg’s tests (p = 0.296) and Egger’s tests (p = 0.097). This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.

Background: Control measures during the coronavirus disease 2019 (COVID-19) outbreak may have limited the spread of infectious diseases. This study aimed to analyse the impact of COVID-19 on the spread of hand, foot, and mouth disease (HFMD) in China. Methods: A mathematical model was established to fit the reported data of HFMD in six selected cities in mainland China from 2015 to 2020. The absolute difference (AD) and relative difference (RD) between the reported incidence in 2020, and simulated maximum, minimum, or median incidence of HFMD in 2015-2019 were calculated. Findings: The incidence and Reff of HFMD have decreased in six selected cities since the outbreak of COVID-19, and in the second half of 2020, the incidence and R eff of HFMD have rebounded. The results show that the total attack rate (TAR) in 2020 was lower than the maximum, minimum, and median TAR fitted in previous years in six selected cities (except Changsha city). For the maximum, median, minimum fitted TAR, the range of RD (%) is 42·20-99·20%, 36·35-98·41% 48·35-96·23% (except Changsha city) respectively. Interpretation: Based on the incidence data of six cities from 2015 to 2019, the SEIAR model demonstrated a significant effect on the incidence of HFMD. During the period of COVID-19, the incidence and R eff of HFMD decreased, the prevention and control measures taken during the period of COVID-19, such as school suspension, home quarantine, closing all kinds of leisure places, wearing masks, advocating frequent hand washing, etc., have not only effectively suppressed the spread of COVID-19 epidemic, but also have significantly contributed to the containment of HFMD transmission. Funding Statement: This study was partly supported by the Bill & Melinda Gates Foundation (INV-005834). Declaration of Interests: The authors declare no conflicts of interests.

Background Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Although public health countermeasures effectively controlled the epidemic in China, non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally. Vaccination is mainly used to prevent COVID-19, and most current antiviral treatment evaluations focus on clinical efficacy. Therefore, we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy. Methods We collected COVID-19 data of Wuhan City from published literature and established a database (from 2 December 2019 to 16 March 2020). We developed an age-specific model to evaluate the effectiveness of antiviral treatment in patients with COVID-19. Efficacy was divided into three types: (1) viral activity reduction, reflected as transmission rate decrease [reduction was set as v (0–0.8) to simulate hypothetical antiviral treatments]; (2) reduction in the duration time from symptom onset to patient recovery/removal, reflected as a 1/γ decrease (reduction was set as 1–3 days to simulate hypothetical or real-life antiviral treatments, and the time of asymptomatic was reduced by the same proportion); (3) fatality rate reduction in severely ill patients (fc) [reduction (z) was set as 0.3 to simulate real-life antiviral treatments]. The population was divided into four age groups (groups 1, 2, 3 and 4), which included those aged ≤ 14; 15–44; 45–64; and ≥ 65 years, respectively. Evaluation indices were based on outbreak duration, cumulative number of cases, total attack rate (TAR), peak date, number of peak cases, and case fatality rate (f). Results Comparing the simulation results of combination and single medication therapy s, all four age groups showed better results with combination medication. When 1/γ = 2 and v = 0.4, age group 2 had the highest TAR reduction rate (98.48%, 56.01–0.85%). When 1/γ = 2, z = 0.3, and v = 0.1, age group 1 had the highest reduction rate of f (83.08%, 0.71–0.12%). Conclusions Antiviral treatments are more effective in COVID-19 transmission control than in mortality reduction. Overall, antiviral treatments were more effective in younger age groups, while older age groups showed higher COVID-19 prevalence and mortality. Therefore, physicians should pay more attention to prevention of viral spread and patients deaths when providing antiviral treatments to patients of older age groups.

Background: The purpose of this research was to investigate whether the modified version of Adjuvant! Online was able to omit chemotherapy (CT) for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and axillary node-negative breast cancer, who are defined as low clinical risk. Methods: From 2010 to 2014, HR-positive, HER2-negative, and node-negative breast cancer patients aged 50 years and older were retrieved from the Surveillance, Epidemiology, and End Results (SEER) 18 database. The propensity score matching method was applied between the no-CT and CT groups. Overall survival (OS) was evaluated using Kaplan-Meier analysis and compared across groups using a log-rank test. Results: A total of 48,857 patients were enrolled. After propensity score matching, the numbers of patients in the no-CT and CT groups were both 3,102. The median follow-up period was 37 months. The 5-year OS rates in the no-CT and CT groups were 92 and 91%, respectively (p = 0.066). In the subgroup with a tumor score (tumor size added to tumor grade) of 2–3, OS was significantly higher in the no-CT group than in the CT group (93 vs. 90%, p < 0.001). In the subgroup with a tumor score of 4, OS was not different between these 2 groups (92 vs. 93%, p = 0.47). Conclusion: This retrospective study provides evidence that CT may not be beneficial to patients 50 years of age or older with HR-positive, HER2-negative, axillary node-negative breast cancer and additionally defined as low clinical risk by a modified version of Adjuvant! Online.

Objective The functions and molecular regulatory mechanisms of miR-193a-3p in cardiac injury induced by obstructive sleep apnea (OSA) are poorly understood. This study aimed to explore the role of miR-193a-3p in intermittent hypoxia(IH)-induced human umbilical vein endothelial cells (HUVECs) injury. Results In this study, we found that IH significantly decreased viability but enhanced cell apoptosis. Concurrently, the miR-193a-3p expression level was increased in HUVECs after IH. Subsequent experiments showed that IH-induced injury was ameliorated through miR-193a-3p silence. Fas apoptotic inhibitory molecule 2 (FAIM2) was predicted by bioinformatics analysis and further identified as a direct target gene of miR-193a-3p. Interestingly, the effect of miR-193a-3p inhibition under IH could be reversed by down-regulating FAIM2 expression. Conclusion In conclusion, our study first revealed that miR-193a-3p inhibition could protect HUVECs against intermittent hypoxia-induced damage by negatively regulating FAIM2. These findings could advance our understanding of the underlying mechanisms for OSA-related cardiac injury. Methods We exposed HUVECs to IH condition; the expression levels of miR-193a-3p were detected by RT-qPCR. Cell viability, and the expressions of apoptosis-associated proteins were examined via CCK-8, and western blotting, respectively. Target genes of miR-193a-3p were confirmed by dual-luciferase reporter assay.

Septic arthritis induced by Staphylococcus aureus (S. aureus) causes irreversible cartilage degradation and subsequent permanent joint dysfunction. Recently, cartilage degradation in osteoarthritis is recognized to be associated with metabolic disorders. However, whether cholesterol metabolism is linked to septic arthritis pathology remains largely unknown. Here, we found that exposure to fermentation supernatant (FS) of S. aureus in chondrocytes resulted in a significant increase in expression of key modulators involved in cholesterol metabolism, including lectin-type oxidized low density lipoprotein receptor 1 (LOX1), cholesterol 25-hydroxylase (CH25H), 25- hydroxycholesterol 7α-hydroxylase (CYP7B1) as well as retinoic acid-related orphan receptor alpha (RORα), a binding receptor for cholesterol metabolites. We further demonstrated that enhancement of CH25H/CYP7B1/RORα axis resulted from FS exposure was mediated by activation of NF-κB signaling, along with upregulation in catabolic factors including matrix metallopeptidases (MMP3 and MMP13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2) in chondrocytes. Exogenous cholesterol acts synergistically with FS in activating NF-κB pathway and increases cholesterol metabolism. While, the addition of tauroursodeoxycholic acid (TUDCA) which promotes cholesterol efflux, resulted in remarkable reduction of intracellular cholesterol level and restoration of balance between anabolism and catabolism in FS treated chondrocytes. Collectively, our data indicated that, in response to FS of S. aureus, NF-κB signaling activation coupled with increased cholesterol metabolism to stimulate catabolic factors in chondrocytes, highlighting cholesterol metabolism as a potential therapeutic target for treating septic arthritis.

Background: Cigarette smoking is a major risk factor for bronchoalveolar epithelial cell (BAEC) injury. Understanding the relevant pathogenesis is important for the treatment of cigarette smoke–related chronic airway diseases such as chronic obstructive pulmonary disease.Methods: In this study, BAECs were cultured in 5% cigarette smoke extract (CSE) or regular culture medium for 24 h. Differentially expressed genes (DEGs) were detected by next-generation RNA sequencing (RNA-seq) and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatic analysis was performed on DEGs. Co-treated BAECs with 5% CSE and the ferroptosis inhibitor, ferrostatin-1 was applied to observe the role of ferroptosis.Results: In the CSE group, 210 upregulated genes and 159 downregulated genes were identified compared with the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were related to oxidative stress and ferroptosis. Ferroptosis-related genes were further verified by qRT-PCR. The mRNA level of GPX4 decreased; the mRNA levels of ACSL4, FTH1 and SLC7A11 increased (p < 0.05). Pretreatment with the ferroptosis inhibitor ferrostatin-1 mitigated CSE-induced ROS accumulation and inflammatory mediator expression in BAECs (p < 0.05).Conclusion: CSE treatment altered ferroptosis-related gene expression patterns in cultured BAECs. Inhibition of ferroptosis reduced the inflammatory response of CSE-treated BAECs. These data provide a better understanding of the underlying molecular mechanisms of CSE-related lung injury.

Background and ObjectivesCurrently, the location of primary tumor was an independent prognostic factor of breast cancer. Tumors in the central and nipple portion (TCNP) had poor prognosis compared to other peripheral quadrants. The breast-conserving therapy (BCT) is becoming increasingly common worldwide in breast cancer operations. However, whether the availability of BCT was performed for TCNP remained a matter of debate. We sought to investigate whether BCT was suitable for TCNP with respect to survival outcomes, compared with mastectomy therapy.MethodsUtilizing the Surveillance, Epidemiology, and End Results (SEER) database, we obtained TCNP breast cancer patients diagnosed during the period of 2010–2015. One-to-one (1:1) propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of BCT and mastectomy groups. Univariate and multivariate Cox proportional hazard models were applied to estimate the factors associated with breast cancer-specific survival (BCSS) and overall survival (OS). Survival analysis was performed with the Kaplan–Meier method.ResultsIn the overall cohort, a total of 9,900 patients were enrolled. We found that patients with BCT showed significantly better BCSS (log-rank, p < 0.001) and OS (log-rank, p < 0.001) than the mastectomy group before PSM. The same finding was also shown in 5,820 patients after PSM. Additionally, none of the subgroups, including age, sex, race, histological grade, AJCC stage, and molecular subtype undergoing mastectomy therapy, had better BCSS than BCT.ConclusionsOur study was the first research to show that BCT exhibited superior prognosis in the cohort of TCNP from SEER databases than mastectomy therapy. This finding could provide a cue for treatment strategies for suitable TCNP patients, especially those with a strong willingness to conserve their breasts.

Despite the adoption of a national immunization program in China, the incidence of mumps remains high. This study aimed to describe the epidemiological characteristics, including the time, region, occupation, and age, of mumps in Wuhan from 2005 to 2018 and to evaluate its transmissibility. In this study, the susceptible–exposed–infectious–asymptomatic–recovered (SEIAR) model fitted the actual incidence data of mumps. The effective reproduction number (Rt) was used to evaluate and compare the transmission capacity in different areas. From 2005 to 2018, there were 36,415 cases. The incidence of mumps was highest among people aged 5–10 years (460.02 per 100,000). The SEIAR model fitted the reported mumps data well (P < 0.01). The median transmissibility (Rt) was 1.04 (range = 0–2.50). There were two peak spreads every year (from March to May and from October to December). The Rt peak always appeared in the first 2 months of the peak incidence rate. The peak time of the epidemic spread of mumps was 1–2 months earlier than the peak incidence rate. The prevention and control measures of vaccination for children aged 5–10 years should be taken before the peak transmission capacity each year, 2 months before the peak of the outbreak, to reduce the spread of mumps.

Obstructive sleep apnea (OSA) has been demonstrated to be associated with liver injury. Nevertheless, the mechanisms linking the two disorders remain largely unexplored to date. Based on UHPLC/Q-TOF MS platform, the present study aimed to study the hepatic metabolomic profiling in a chronic intermittent hypoxia (CIH) mouse model to identify altered metabolites and related metabolic pathways. C57BL/6 Mice (n = 12 each group) were exposed to intermittent hypoxia or control conditions (room air) for 12 weeks. At the end of the exposure, liver enzymes and histological changes were assessed. Untargeted metabolomics approach by UHPLC/Q-TOF MS and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to screen altered metabolites in mice liver. Bioinformatics analyses were applied to identify the related metabolic pathways. CIH treatment caused a remarkable liver injury in mice. A total of 27 differential metabolites in negative ion mode and 44 in positive ion mode were identified between the two groups. These metabolites were correlated to multiple biological and metabolic processes, including various amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, ferroptosis, etc. three differential metabolites including glutathione, glutathione disulfide, arachidonic acid (peroxide free) were identified in the ferroptosis pathway. CIH was associated with a significant metabolic profiling change in mice liver. The metabolites in amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and ferroptosis played an important role in CIH-induced liver injury. These findings contribute to a better understanding of the mechanisms linking OSA and liver injury and help identify potential therapeutic targets.

Obstructive sleep apnea syndrome (OSAS) was suggested to exert an effect on renal function. However, the specific mechanism was still unknown. We try to find the association among OSAS, adiponectin, and cystatin C and the effect of adiponectin on renal function in OSAS patients. Seventeen healthy men and seventy-three men which only had OSAS were included in the end. Apnea-hypopnea index (AHI), oxygen desaturation index (ODI), the percentage of total sleep time spent with SpO2

The efficacy of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on visceral adipose tissue (VAT) yielded conflicting results. This meta-analysis was performed to assess whether OSA treatment with CPAP could reduce VAT. The PubMed, Cochrane Library, Embase, and Web of Science were searched before April 2019. Information on characteristics of study participants, pre- and post-CPAP treatment of VAT, and study design was utilized for analysis. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to fully analyze the overall effects. Eleven studies were obtained and the meta-analysis was performed using RevMan v.5.2 and STATA 12.0. A total of 11 studies (16 cohorts) were pooled into meta-analysis, which included 398 patients. The value of VAT before and after CPAP treatment showed no change in OSA patients (SMD = − 0.02, 95% CI − 0.16 to 0.12, z = 0.24, p = 0.81). Subgroup analyses were further conducted, which revealed that age, gender distribution, baseline body mass index, daily duration, CPAP therapy duration, measure, sample size, and study design did not affect the results. This meta-analysis revealed that CPAP therapy has no effect on VAT in OSA patients. Further large-scale, well-designed randomized controlled trials are required to address this issue.

Iatrogenic radial nerve injures are a common complication during the placement of external fixator pins at the lateral aspect of the humeral shaft. This study uses a three-dimensional measurement technique to locate a safe entry point for humeral pins when externally fixating the elbow.

Yichang is a city in central China in the Hubei Province. This study aimed to estimate the dynamics of the transmissibility of hepatitis C using a mathematical model and predict the transmissibility of hepatitis C in 2030. Data of hepatitis C cases from 13 counties or districts (cities) in Yichang from 2008 to 2016 were collected. A susceptible-infectious-chronic-recovered (SICR) model was developed to fit the data. The transmissibility of hepatitis C at the counties or districts was calculated based on new infections (including infected or chronically infected cases) reported monthly in the city caused by one infectious individual (MNI). The trend of the MNI was fitted and predicted using 11 models, with the coefficient of determination (R2 ) was being used to test the goodness of fit of these models. A total of 3065 cases of hepatitis C were reported in Yichang from 2008 to 2016. The median MNI of Yichang was 0.0768. According to the fitting results and analysis, the trend of transmissibility of hepatitis C in Yichang City conforms with the logarithmic (R2 = 0.918, p

BackgroundThyroid nodules are a common clinical problem and some are potentially cancerous; however, little is known about the prevalence of thyroid nodules in China. The objective of this study was to investigate the prevalence of thyroid nodules in a healthy Chinese population.MethodsWe reviewed electronic medical records of 13,178,313 participants from 30 provinces and regions who received health examinations and underwent thyroid ultrasound at Meinian Onehealth Healthcare in 2017. Among them, 6,192,357 were excluded based on predefined criteria. All thyroid nodules were diagnosed by ultrasonography, and standardized protocols were adopted for data collection, quality control, and data management.ResultsA total of 6,985,956 participants (mean age: 42.1 ± 13.1 years) were included in this study. The overall prevalence of thyroid nodules was 36.9% (95% CI, 35.7%–38.1%; age- and sex-standardized prevalence 38.0% [95% CI, 37.0%–39.1%]). The prevalence of thyroid nodules in females (44.7% [95% CI, 43.4%–45.9%], age-standardized prevalence: 45.2% [95% CI, 44.1%–46.4%]) was significantly higher than that in males (29.9% [95% CI, 28.8%–31.0%], age-standardized prevalence 31.2% [95% CI, 30.1%–32.2%]; P < 0.001). The prevalence of thyroid nodules decreased from ConclusionThis study provides the first nationwide analysis of the prevalence of thyroid nodules in China. Our results showed that the prevalence of thyroid nodules was high in health screening Chinese people with regional-specific patterns.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is regionally distributed in Asia, with high fatality. Constructing the transmission model of SFTS could help provide clues for disease control and fill the gap in research on SFTS models. Methods We built an SFTS transmission dynamics model based on the susceptible–exposed–infectious–asymptomatic–recovered (SEIAR) model and the epidemiological characteristics of SFTS in Jiangsu Province. This model was used to evaluate the effect by cutting off different transmission routes and taking different interventions into account, to offer clues for disease prevention and control. Results The transmission model fits the reported data well with a minimum R2 value of 0.29 and a maximum value of 0.80, P Conclusions The model we have built can be used to simulate the transmission of SFTS to help inform disease control. It is noteworthy that cutting off the environment-to-humans transmission route in the model had the greatest effect on SFTS prevention and control. Graphical Abstract

Background During the period of the coronavirus disease 2019 (COVID-19) outbreak, strong intervention measures, such as lockdown, travel restriction, and suspension of work and production, may have curbed the spread of other infectious diseases, including natural focal diseases. In this study, we aimed to study the impact of COVID-19 prevention and control measures on the reported incidence of natural focal diseases (brucellosis, malaria, hemorrhagic fever with renal syndrome [HFRS], dengue, severe fever with thrombocytopenia syndrome [SFTS], rabies, tsutsugamushi and Japanese encephalitis [JE]). Methods The data on daily COVID-19 confirmed cases and natural focal disease cases were collected from Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial CDC). We described and compared the difference between the incidence in 2020 and the incidence in 2015–2019 in four aspects: trend in reported incidence, age, sex, and urban and rural distribution. An autoregressive integrated moving average (ARIMA) (p, d, q) × (P, D, Q)s model was adopted for natural focal diseases, malaria and severe fever with thrombocytopenia syndrome (SFTS), and an ARIMA (p, d, q) model was adopted for dengue. Nonparametric tests were used to compare the reported and the predicted incidence in 2020, the incidence in 2020 and the previous 4 years, and the difference between the duration from illness onset date to diagnosed date (DID) in 2020 and in the previous 4 years. The determination coefficient (R2) was used to evaluate the goodness of fit of the model simulation. Results Natural focal diseases in Jiangsu Province showed a long-term seasonal trend. The reported incidence of natural focal diseases, malaria and dengue in 2020 was lower than the predicted incidence, and the difference was statistically significant (P P P Conclusions Interventions for COVID-19 may help control the epidemics of natural focal diseases in Jiangsu Province. The reported incidence of natural focal diseases, especially malaria and dengue, decreased during the outbreak of COVID-19 in 2020. COVID-19 prevention and control measures had the greatest impact on the reported incidence of natural focal diseases in males and people in the 20–60-year age group. Graphical Abstract

Background Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province. Methods We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness. Results From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R2 = 0.655, P TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days). Conclusions HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route. Graphic Abstract

BackgroundPalmitoylation is essential for classic hallmarks of cancer, regulating protein stability and protein-protein interactions. Targeting palmitoylation or palmitoyltransferases has become a novel strategy for therapeutic intervention in cancer. However, few studies have reported the expression pattern, pathological functions and underlying mechanism of ZDHHC22 in breast cancer.MethodsPublic database analysis, quantitative reverse transcription PCR, and western blot were used to analyze ZDHHC22 expression. Methylation-specific PCR was employed to detect the promoter methylation status. Expression of mTOR was examined by immunofluorescence staining and western blots, and palmitoylation of mTOR was detected by acyl-biotin exchange assays. Cellular functions were evaluated via corresponding molecular biological and cellular approaches. Nude mice were used to generate a xenograft tumor model.ResultsWe investigated the expression profiles of 23 palmitoyltransferases using data from The Cancer Genome Atlas and found that ZDHHC22 is frequently expressed at minimal levels in multiple cancers. Downregulation of ZDHHC22 is associated with methylation of its promoter in breast cancer. Ectopic ZDHHC22 expression inhibits the malignant properties of breast cancer both in vitro and in vivo. The enzyme-active site-mutation ZDHHC22-(C111A) mutation reversed these effects, demonstrating that ZDHHC22 suppresses the malignant properties of breast cancer through palmitoylation. Bioinformatics analysis predicted mTOR as the substrate of ZDHHC22. mTOR palmitoylation for the first time was detected and we found ZDHHC22 reduced the stability of mTOR via regulating the palmitoylation of mTOR. Additionally, mTOR expression was frequently negatively correlated with ZDHHC22 in tamoxifen-resistant breast cancer cells and ectopic ZDHHC22 could restore endocrine sensitivity in tamoxifen-resistant breast cancer cell line.ConclusionOur results demonstrating the hypermethylated status and potential tumor suppressor function of ZDHHC22 in breast cancer for the first time established a regulatory mechanism between ZDHHC22 and mTOR palmitoylation, which may pave the way for the development of promising therapeutics that restore endocrine sensitivity.

Background: With the strength intervention of China, the outbreak of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) had a great control effect. The measures may influence the development and progression of others infectious diseases.Method: The data of daily coronavirus virus disease 2019 (COVID-19) confirmed cases from January 3, 2020 to April 30, 2020 and natural focal disease cases from January, 2005 to April, 2020 were collected from Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial CDC). We describe and compare the data of natural focal diseases from January to April, 2020 with the same months from 2015 to 2019 in the four aspects: trend of incidence, regional, age and sex distribution. Nonparametric tests were used to analyzed to the difference between the duration from onset of illness to date of diagnosis of natural focal diseases and the same period of the previous year. Results: The incidence of malaria in February (0.9 per 10,000,000 people), March (0.3 per 10,000,000 people) and April (0.1 per 10,000,000 people) 2020 less than the lower limit for range of February (1.6-4.5 per 10,000,000 people), March (0.8-3.3 per 10,000,000 people) and April (1.0-2.9 per 10,000,000 people) from 2015 to 2019 respectively. The incidence of brucellosis in February was 0.9 (per 10,000,000 people), less than the lower limit for the range from 2015 to 2019 (1.6-4.5 per 10,000,000 people). The incidence of hemorrhagic fever (HF) in March was 1.0 (per 10,000,000 people), less than the lower limit for the range from 2015 to 2019 (1.4-2.6 per 10,000,000 people). However, the incidence of Severe Fever with Thrombocytopenia Syndrome (SEFT) in March was 0.3 (per 10,000,000 people), higher than the upper limit for the range from 2015 to 2019 (0.0-0.1 per 10,000,000 people). Furthermore, we respectively observed the incidence with various degree of reduction in male, 20-60 years old and both rural and urban areas. Conclusions: In Jiangsu province, the incidence of natural focal diseases decreased during the outbreak of COVID-19 in 2020, especially malaria, HF and SEFT. The impact of interventions were felt most by male individuals within the age group of 20-50 years. The interventions for COVID-19 may control the epidemics of natural focal diseases.

Increasing medical researche shows that endothelial dysfunction is one of the important causes of various cardiovascular diseases related to chronic intermittent hypoxia (CIH). This study aimed to identify target proteins in CIH-related vascular dysfunction. A comparative proteomics analysis was conducted in aortic samples of rats treated with CIH and controls with normoxia. Bioinformatics analyses were performed to determine the potential roles of major proteins. The expressions of target proteins were measured by western blotting. Cell apoptotic ratio was detected by flow cytometer. A total of 3,593 proteins in aortic tissues of rats were quantified. Ninety-two upregulated proteins and 468 downregulated proteins were identified when the cutoff of fold change was set at 1.5 (CIH vs. normoxia). The results of bioinformatics analysis revealed that the differentially expressed proteins were enriched in the processes of energy metabolism and lipid metabolism. The reduced expression level of peroxisome proliferator–activated receptor γ (PPARγ) protein was identified in thoracic aortic tissues of rats with CIH by proteomics analysis and western blotting. In intermittent hypoxia-treated rat aortic endothelial cells, PPARγ protein levels were reduced, and the apoptosis rate and caspase-3 and Bax protein levels were markedly elevated. Importantly, forced expression of PPARγ by rosiglitazone in intermittent hypoxia-treated rat aortic endothelial cells not only attenuated caspase-3 and Bax protein levels but also reduced the rate of apoptosis. PPARγ is critical in endothelial dysfunction of rats with CIH. Additional studies on these differentially expressed proteins associated with CIH-related endothelial dysfunction are necessary.

Background Some studies have reported a relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in pediatric population. However, this issue remains controversial. Objectives The purpose of the present study was to investigate the association between OSA and NAFLD in pediatric population. Methods We systematically searched PubMed, Web of Science, Embase for eligible studies. The data involving markers of NAFLD including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic inflammation, hepatic fibrosis of both OSA group and control group were extracted. Pooled standardised mean difference (SMD) and weighted mean difference (WMD) were appropriately calculated through a fixed or random-effect model. Results Nine cross-sectional studies with 1133 children and adolescents were included. OSA was significantly associated with ALT, AST, and NAFLD fibrosis stage, but not NAFLD inflammation grade. Subgroup analysis indicated that both mild OSA and severe OSA were significantly associated with elevated ALT and AST. Furthermore, in the studies with all main confounding factors (age, gender, and BMI) matched, OSA group had higher ALT and AST levels than control group. Conclusions This meta-analysis suggested that OSA was associated with NAFLD evidenced by elevated liver enzymes and progressive hepatic fibrosis in pediatric population. Screening and monitoring of NAFLD in pediatric patients with obesity-related OSA are necessary.

Objectives Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19. Methods A retrospective study was performed in a non-intensive care unit (ICU) ward in Jinyintan Hospital from 2 February 2020 to 20 March 2020. COVID-19 was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of pharyngeal swab specimens. The confirmed patients were divided into the umifenovir group and the control group according to the use of umifenovir. The main outcomes were the rate of negative pharyngeal swab tests for SARS-CoV-2 within 1 week after admission and the time for the virus to turn negative. The negativity time of SARS-CoV-2 was defined as the first day of a negative test if the nucleic acid of SARS-CoV-2 was negative for two consecutive tests. Results A total of 81 COVID-19 patients were included, with 45 in the umifenovir group and 36 in the control group. Baseline clinical and laboratory characteristics were comparable between the two groups. Thirty-three out of 45 (73%) patients in the umifenovir group tested negative for SARS-CoV-2 within 7 days after admission, the number was 28/36 (78%) in the control group (p 0.19). The median time from onset of symptoms to SARS-CoV-2 turning negative was 18 days (interquartile range (IQR) 12–21) in the umifenovir group and 16 days (IQR 11–21) in the control group (p 0.42). Patients in the umifenovir group had a longer hospital stay than patients in the control group (13 days (IQR 9–17) vs 11 days (IQR 9–14), p 0.04). No deaths or severe adverse reactions were found in both groups. Discussion Umifenovir might not improve the prognosis or accelerate SARS-CoV-2 clearance in non-ICU patients. A randomized control clinical trial is needed to assess the efficacy of umifenovir.

It is still controversial if the continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea (OSA) can markedly influence an effect on visceral adipose tissue (VAT). The current study aimed to assess the efficacy of CPAP interventions in reducing VAT in OSA patients. The Web of Science, PubMed, Embase, and Cochrane Library (up to December, 2019) were searched for randomized trials that assessed the effect of CPAP therapy in decreasing VAT in OSA patients. Information on the study, pre- and post-CPAP treatment of VAT, and patient characteristics were extracted for analysis. The standardized mean difference (SMD) was applied to measure the summary estimates. The analysis was conducted with STATA 13.0 and RevMan v.5.3. Five studies (6 cohorts) that involved 169 patients were enrolled in the meta-analysis. There was no significant change of VAT in patients with OSA before and after CPAP treatment (SMD = − 0.00, 95% CI = − 0.21 to 0.21, z = 0.01, p = 0.99). Subgroup analyses further demonstrated that the results were not influenced by CPAP therapy duration, patient age, sample size, or baseline body mass index. Among the patients with OSA, our meta-analysis revealed that treatment with CPAP does not significantly lead to a reduction of VAT. High-quality randomized controlled trials may provide further clarifying information.

Background Chronic intermittent hypoxia (CIH) involves substantial cortico-hippocampal injury, causing impairments of neurocognitive, respiratory, and cardiovascular functions. Long non-coding RNAs (lncRNAs) participate in CIH functions and development. Therefore, we explored the mechanisms involving lncRNA maternally expressed gene 3 (MEG3) regulating the aortic endothelial function of CIH mice via regulation of microRNA-135a (miR-135a) and the hypoxia-inducible factor (HIF)-1α. Methods Expression of MEG3, miR-135a, and HIF-1α in CIH mice and CIH-treated cells was detected. Then, the apoptosis and proliferation of the aortic endothelial cells were examined to verify whether miR-135a and HIF-1α participated in CIH. Next, the interactions between MEG3, miR-135a, and HIF-1α were explored. Later, the effects of MEG3/miR-135a/HIF-1α on the expression of proliferation- and apoptosis-related factors and aortic injury were investigated via gain- and loss-of function studies both in vivo and in vitro. Results MEG3 and HIF-1α were highly expressed while miR-135a was poorly expressed in CIH mice and CIH-modeled cells. Moreover, miR-135a targeted HIF-1α to promote cell proliferation and inhibit apoptosis. MEG3 regulated HIF-1α expression by competitively binding to miR-135a. More importantly, we found that the silencing of MEG3/HIF-1α and the overexpression of miR-135a inhibited the apoptosis and injury of aortic endothelial cells while promoting cell proliferation in CIH mice. Conclusions Altogether, silencing of MEG3 suppressed the aortic endothelial injury and cell apoptosis in CIH mice by downregulating HIF-1α through sponging miR-135a, providing evidence of a potential therapeutic target for CIH.

Background: Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Only drugs or vaccines can eliminate the virus. Methods: We adopted our age-specific transmission model by susceptible-exposed-infectious -critically ill-asymptomatic-removed (SEICAR) model. Effects of different drug types were simulated by changing transmission rate (β), critical case fatality rate (fc), and disease duration of each age group. Evaluation indexes were based on outbreak duration(OD), cumulative number of cases(CNC), total attack rate(TAR), peak date(PD), number of peak cases(NPC), and case fatality rate(f). Findings: When without intervention, changing in β and disease duration, as the age increased, OD decreased, TAR increased, PD advanced, CCN and NPC initially increased and then decreased, while f decreased first and then increased. When disease duration and β remained unchanged, changing fc did not affect the epidemic. All age groups had 40% shorter disease duration but unchanged fc, while β was reduced by 60%, which reduced TAR of group 1 (≤14 years) from 2·35% to 0·09%; f of group 4 (≥65 years) was reduced from 1·04% to 0·05%. Interpretation: Drugs had different age-dependent effects. If a drug can control the disease duration or β of all age groups, younger people would have the fastest transmission control and seniors will have the best improvement in disease severity. Funding: The Bill & Melinda Gates Foundation (INV-005834); the Science and Technology Program of Fujian Province (No: 2020Y0002), and the Xiamen New Coronavirus Prevention and Control Emergency Tackling Special Topic Program (No: 3502Z2020YJ03). Declaration of Interests: The authors declare no competing interests.

Long non-coding RNAs (lncRNAs) are a recently identified class of regulatory molecules involved in the regulation of numerous biological processes, but their functions in a rat model of chronic intermittent hypoxia (CIH) remain largely unknown. Therefore, for further investigation, we aimed to explore lncRNA expression profiles and reveal their potential functional roles in rat models of CIH. We used a well-established CIH rat model and conducted lncRNA microarray experiments on the heart samples of rats with CIH and under normoxia control. Differentially expressed lncRNAs and mRNAs were identified via fold-change filtering and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics analyses were applied to reveal the potential roles of key lncRNAs. Co-expression analysis was conducted to determine the transcriptional regulatory relationship of lncRNAs and mRNAs between the two groups. Our data indicated that 157 lncRNAs and 319 mRNAs were upregulated, while 132 lncRNAs and 428 mRNAs were downregulated in the rat model of CIH compared with sham control. Pathway analyses showed that 31 pathways involved in upregulated transcripts and 28 pathways involved in downregulated transcripts. Co-expression networks were also constructed to explore the potential roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, XR_596701, XR_344474, XR_600374, ENSRNOT00000065561, XR_590196, and XR_597099, were validated by the use of qRT-PCR. The present study first revealed lncRNAs expression profiles in a rat model of CIH, providing new insight into the pathogenesis of obstructive sleep apnea-induced cardiovascular disease.

Purpose Growing evidence has revealed that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes. This study aimed to assess the association between glycometabolism and NAFLD in patients with obstructive sleep apnea (OSA). Methods Patients with suspected OSA were enrolled consecutively and then underwent polysomnography, liver ultrasound, and biochemical measurements. Logistic regressions were used to identify factors associated with NAFLD. Results In total, 415 patients were included. The prevalence of NAFLD in the non-OSA, mild OSA, moderate OSA, and severe OSA groups was 37.21%, 69.09%, 68.34%, and 78.08%, respectively. Stepwise logistic regression suggested that percentage of total sleep time spent with oxygen saturation of

// Kai-Xiong Liu 1, 2, 3 , Qin Chen 4 , Gong-Ping Chen 1, 2, 3 , Jian-Chai Huang 1, 2, 3 , Jie-Feng Huang 1, 2, 3 , Xin-Ru He 1, 2, 3 , Ting Lin 1, 2, 3 and Qi-Chang Lin 1, 2, 3 1 Department of Respiratory Disease, The First Affiliated Hospital, Fujian Medical University, China 2 Laboratory of Respiratory Disease of Fujian Medical University, Fuzhou, China 3 Fujian Provincial Sleep-disordered Breathing Clinic Center, Fuzhou, China 4 Integrated Chinese and Western Medicine Colleges, Fujian University of Traditional Chinese Medicine, Fuzhou, China Correspondence to: Qi-Chang Lin, email: chang4e@126.com Keywords: microRNA-218; intermittent hypoxia-inducible factor-1α; apoptosis; normal mice aortic endothelial cells Received: August 18, 2017 Accepted: September 22, 2017 Published: October 26, 2017 ABSTRACT Objective: To investigate the effects of miR-218 on expression of hypoxia-inducible factors 1α (HIF-1α), vascular endothelial growth factor (VEGF) and cell apoptosis in normal mice aortic endothelial cells under intermittent hypoxia (IH) condition. Methods: Anti-miR-218 inhibitor, miR-negative control and miR-218 mimic were used to tranfect the cells in different groups under IH condition. Both RT-PCR and Western blot were used to determine the expressions of HIF-1α and VEGF. Akt, p-Akt and cell apoptosis related proteins bcl-2, bax and caspase-3 and roundabout 1 (Robo1) were measured using Western blot. Cell apoptosis was evaluated by flow cytometry. Statistical analysis was performed using SPSS 18.0. Results: Expression of miR-218 was significantly up-regulated in the IH group and was significantly inhibited when cells were transfected with miR-218 inhibitor. Down regulation of miR-218 could reduce the expression of HIF-1α and VEGF under intermittent hypoxia condition. In cells transfected with miR-218 mimic, expression of HIF-1α and VEGF significantly increased compared with the control. However, when treated with LY294002, the expression of HIF-1α and VEGF both decreased. Apoptosis assay showed that down regulation of miR-218 could inhibit intermittent hypoxia induced cell apoptosis, decrease expression of caspase-3 and bax and increase expression of bcl-2 under intermittent hypoxia condition. At last, silencing Robo1 could significantly enhance the expression of HIF-1α under IH condition. Conclusion: Inhibition of miR-218 could reduce the expression of HIF-1α and protect against IH-induced apoptosis in mice aortic endothelial cells. The effects were associated with PI3K/AKT pathway and might through targeting of Robo1.

Obstructive sleep apnea syndrome (OSAS) is reported to have an association with bone mineral density (BMD). However, the underlying mechanism is far from clear. The aim of this study was to investigate the relationship between OSAS, bone turnover markers, and BMD and to evaluate the effect of adiponectin on BMD in patients with OSAS. Seventy-one male patients with OSAS and 13 male control subjects were enrolled in this study. Serum adiponectin, calcium, phosphorus, 25-hydroxyvitamin-D3, β-isomerized form C-terminal telopeptide of type I collagen, osteocalcin, and procollagen type 1 N-propeptide were measured in all subjects, and BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) in the lumbar spine (L1–L4), the femoral neck, and the hip total. No statistically significant differences were found between the studied groups in terms of demographic data and bone turnover markers. Serum adiponectin significantly decreased with the aggravation of OSAS. Compared with subjects without OSAS, those with OSAS had a higher hip total BMD and t scores (p = 0.027 and p = 0.028). The significant negative association was found between serum adiponectin levels and hip total BMD. After adjusting for confounders, adiponectin as well as oxygen desaturation index (ODI) significantly predicted the hip total BMD (β = −0.232, p = 0.005 and β = 0.226, p = 0.037). In male subjects, the presence of obstructive sleep apnea syndrome is associated with higher bone mineral density of the hip. These findings suggest that serum adiponectin may be an underlying mediator for BMD in OSAS.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). However, studies provide conflicting results on the effects of CPAP on subcutaneous adipose tissue (SAT) in patients with OSA. We therefore performed a meta-analysis to evaluate whether or not CPAP has an effect on SAT in patients with OSA. Studies were retrieved by searching the Cochrane Library, Web of Science, Embase, and Pubmed. Information on study and patient characteristics, study design, and SAT pre- and post-CPAP treatment was extracted for analysis. Different methods for measurement of SAT were also notated. Standardized mean difference (SMD) and 95% confidence interval (CI) were measured to estimate the change in SAT before and after CPAP treatment. Meta-analysis was performed using the RevMan v.5.3 and Stata 14.0. A total of 10 studies met inclusion criteria encompassing 309 patients in the final analysis. The pooled estimate showed that CPAP treatment resulted in no significant change in SAT (SMD = − 0.014, 95% CI = − 0.161 to 0.133, p = 0.896). Meta-regression analyses revealed no predictor, including methods of measuring SAT, that influenced the CPAP effect on SAT. Our meta-analysis demonstrated that after CPAP therapy, there was no significant change in SAT in patients with OSA.

Adequate sleep is significant for human to actively pursue daily activity. On the other hand, insomnia is directly proportional to aging and health deterioration. Sleep disorder classification is important for medical scientists as well as machine learning researchers. In the paper, we have developed a sleep disorder classification method for Electrocardiogram (ECG) data. The data set have two labels; sleep disorder or not, which can be categorized as binary output. As a result, logistic regression is used as classification technique. For initial experimentation, an existing data set is used. The data set consists of every 10 second data up to 6000 seconds for 35 patients. We have used 70% data for training, and 30% data for testing purpose. Our results from logistic regression show that the logistic regression method is efficient to detect sleep disorders. The prediction result is found to be 59%. The future research in this direction would be to take data from hospitals and use our developed algorithm for sleep disorder classification and prediction.

According to the American Academy of Sleep Medicine (AASM), patients with apnea of 10 seconds or more , and more than 5 times per hour can be diagnosed with sleep disorders. The current gold standard for detecting this type of people with sleep disorder is Polysomnography (PSG). But more than 80% Obstructive Sleep Apnea(OSA) patients of the Sleep Disorder(SD) have not been detected. The reason is that the current configuration of PSG is insufficient in more than 2,500 sleep labs in the United States , and that the lack of manpower of sleep professional technicians who analyze PSG signal has caused many OSA patients to be diagnosed in a timely and effective manner. It is no effective measures to reduce the risk even after OSA patients have been diagnosed. Current medical treatments are either surgical or a lifelong Continuous positive dual channel air pressure ventilator(CPAP). Domestic research shows that OSA patients have poor sleep at night and sleepiness during the day. It often results in inefficient work and causes many traffic accidents. Therefore, how to take effective monitoring measures for these already diagnosed OSA patients has become an urgent problem to be solved.This paper extracts an interactive monitoring system for patients with OSA based on the Internet of Things(IoT) framework. It can reduce the timely rescue of OSA patients when they are in danger in field operations. At the same time, through the interactive function of this indicator mark, the anxiety during the waiting process can be reduced. It is also convenient for the peers to report the progress of the patient in time. The specific method is to use the existing IoT framework. The IoT data acquisition layer uses wearable sensors to collect vital signs of patients, with emphasis on ECG and SpO2 signals. The network layer transmits the collected physiological signals to the Beidou indicator using the Bluetooth Low Energy (BLE) protocol. The platform layer adopts the mature rescue interaction platform of Beidou&GPS. The previous GPS indicator has no short message function, and the patient can only passively wait for rescue. Positional standard is improved through Beidou model, and the short message interaction function has been added. Then the patient can report the progress of the disease in time while waiting for the rescue. After our simulation test, the effectiveness of the OSA patient rescue monitoring system based on the IoT framework has been greatly improved, especially in outdoor work, where the mobile phone signal coverage is relatively weak. The short message function added by the Beidou indicator can be used to provide timely progress of the patient's condition, and provide the medical rescue team with the data support to offer a more accurate rescue plan. After a comparative trial, the rescue rate of the OSA patients with the detection device of this article increased by 10 percentage points compared with the rescue rate with only GPS satellite phones.

MicroRNAs (miRNAs) have emerged as key modulators in the pathophysiologic processes of cardiovascular diseases. However, its function in cardiac injury induced by obstructive sleep apnea (OSA) remains unknown. The aim of the current study was to identify the effect and potential molecular mechanism of miR-146a-5p in intermittent hypoxia(IH)- induced myocardial damage. We exposed H9c2 cells to IH condition; the expression levels of miR-146a-5p were detected by RT-qPCR. Cell viability, cell apoptosis, and the expressions of apoptosis-associated proteins were assessed via Cell Counting Kit-8 (CCK-8), flow cytometry, and western blotting, respectively. Target genes of miR-146a-5p were confirmed by dual-luciferase reporter assay. IH remarkably lowered viability but enhanced cell apoptosis. Concomitantly, the miR-146a-5p expression level was increased in H9c2 cells after IH. Subsequent experiments showed that IH-induced injury was alleviated through miR-146a-5p silence. X-linked inhibitor of apoptosis protein (XIAP) was predicted by bioinformatics analysis and further confirmed as a direct target gene of miR-146a-5p. Surprisingly, the effect of miR-146a-5p inhibition under IH may be reversed by downregulating XIAP expression. In conclusion, our results demonstrated that miR-146a-5p could attenuate viability and promote the apoptosis of H9c2 by targeting XIAP, thus aggravating the H9c2 cell injury induced by IH, which could enhance our understanding of the mechanisms for OSA-associated cardiac injury.

Purpose. The efficacy of obstructive sleep apnea (OSA) therapy with continuous positive airway pressure (CPAP) on uric acid (UA) yielded conflicting results. This meta-analysis was performed to assess whether OSA treatment with CPAP could reduce UA levels. Methods. The Web of Science, Cochrane Library, Embase, and PubMed were searched before March 2019. Information of patients, study design, and pre- and post-CPAP treatment of UA was utilized for analysis. The overall effects were analyzed via the standardized mean difference (SMD) with a 95% confidence interval (CI). Five studies were obtained and the meta-analysis was performed using Stata 12.0 and Review Manager 5.2. Results. A total of 5 studies with 6 cohorts (2 RCT and 3 observational studies) involving 270 patients were pooled into meta-analysis. There was no change of UA levels before and after CPAP treatment in OSA patients (SMD=‐0.20, 95% CI: -0.78 to 0.37, Z=0.69, p=0.49). Subgroup analysis showed that the outcomes were not affected by age of patients, gender distribution, baseline body mass index, daily duration, duration of CPAP treatment, sample size, and study design. Conclusions. This meta-analysis revealed that CPAP treatment has no effect on UA in OSA patients. Further well-designed, large-scale randomized controlled trials are required to address this issue.

Continuous positive airway pressure (CPAP) is the current gold-standard treatment for moderate to severe obstructive sleep apnea (OSA), and upper airway anatomy plays an increasingly important role in evaluating the efficacy of CPAP therapy. The aim of this observational study was to investigate the influence of upper airway anatomy on CPAP titration in OSA patients assessed by computed tomography (CT) during Müller's maneuver.Consecutive patients under investigation for OSA by undergoing polysomnography and CT scan of the upper airway while awake were enrolled. Successful full-night manual titration was performed to determine the optimal CPAP pressure level for OSA patients in supine position using a nasal mask.A total of 157 subjects (134 males and 23 females) were included. Both apnea-hypopnea index (AHI) and LaSO2 significantly correlated with CPAP titration level, upper airway length (UAL), distance from mandibular plane to hyoid bone (MPH), and neck circumference (all p 0.05). There were significant positive correlations between CPAP titration level and UAL (r = 0.348, p = 0.000) and MPH (r = 0.313, p = 0.002). Stepwise multiple linear regression analyses were performed to evaluate the independent predictors of AHI, LaSO2, and CPAP titration level. CPAP titration level was identified as an independent explanatory variable for AHI and LaSO2 after adjustment for confounders. Multiple linear regression analyses also indicated that body mass index (BMI) and UAL were independently associated with CPAP titration level (all p 0.05).Upper airway abnormalities combined with anthropometric parameters play important roles in CPAP titration for OSA patients, providing additional insight into the factors influencing OSA treatment strategies. UAL and BMI should be taken into consideration when choosing CPAP titration level to improve CPAP compliance.

Importance Steroid hormone receptors, including estrogen receptor (ER) and progesterone receptor (PR), are crucial biomarkers in breast cancer (BC). However, limited data are available regarding single hormone receptor–positive (ER-positive/PR-negative and ER-negative/PR-positive) subtypes, rendering treatment decision and survival forecast difficult in patients with these BC subtypes. Objective To investigate the clinicopathological characteristics and BC-specific survival (BCSS) of patients with single hormone receptor–positive BC. Design, Setting, and Participants In this cohort study, data on patients diagnosed with BC between 1990 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results database (N = 1 158 032). Patients lacking information on ER status, PR status, or BCSS were excluded (n = 334 633). Comparisons were performed between single hormone receptor–positive BC and double hormone receptor–positive/double hormone receptor–negative BC. The dates of analysis were September 1, 2018, to June 31, 2019. Main Outcomes and Measures The BCSS of patients with single hormone receptor–positive BC. Results This cohort study included 823 399 patients with BC (818 002 women and 5397 men). The median (range) age at diagnosis was 60 (8-108) years, and the median (range) follow-up duration was 71 (0-311) months. The percentages of ER-positive/PR-positive, ER-positive/PR-negative, ER-negative/PR-positive, and ER-negative/PR-negative cases were 67.2%, 12.2%, 1.6%, and 19.0%, respectively. Single hormone receptor–positive subtypes showed distinct clinical characteristics compared with double hormone receptor–positive/double hormone receptor–negative subtypes. Multivariable Cox proportional hazards regression analysis showed that patients with ER-positive/PR-negative (hazard ratio [HR], 1.36; 95% CI, 1.34-1.38) and ER-negative/PR-positive (HR, 1.61; 95% CI, 1.55-1.67) tumors had worse BCSS than patients with the ER-positive/PR-positive subtype. In contrast, patients with ER-positive/PR-negative (HR, 1.27; 95% CI, 1.24-1.29) and ER-negative/PR-positive (HR, 1.07; 95% CI, 1.03-1.11) tumors had better BCSS than patients with the ER-negative/PR-negative subtype. The BCSS was statistically significantly worse in patients with ER-negative/PR-positive tumors than in patients with ER-positive/PR-negative tumors (HR, 1.18; 95% CI, 1.14-1.23). Conclusions and Relevance In this cohort study, statistically significant distinctions between survival rates of patients with single hormone receptor–positive BC vs double hormone receptor–positive/double hormone receptor–negative BC were observed. Different strategies may be required for patients with single hormone receptor–positive tumors to ensure optimal treatment and maximum benefits from therapies.

Obstructive sleep apnea (OSA) is related to endothelin-1 (ET-1). Continuous positive airway pressure (CPAP) is an effective therapy for OSA. However, the effectiveness of CPAP on ET-1 levels in patients with OSA yielded contradictory results. We conducted a meta-analysis to assess the effect of CPAP on ET-1 levels in OSA. The Embase, and Cochrane Library and PubMed were searched before March, 2018. The overall effects were measured by the standardized mean difference (SMD) with a 95% confidence interval (CI). Ten studies were included and the meta-analysis was conducted using Stata 14.0. 10 studies involving 375 patients were included in the meta-analysis. The result showed that there was a significant reduction in ET-1 levels in OSA patients before and after CPAP therapy (SMD = − 0.74, 95% CI = − 1.30 to − 0.17, z = 2.56, p = 0.01). Further, subgroup analysis demonstrated that Apnea–Hypopnea Index (AHI), CPAP therapy duration, and sample size also affected CPAP therapy. Our meta-analysis indicated that CPAP treatment among OSA patients was significantly was related to a decrease in ET-1 levels. Further prospective long-term studies with a larger number of patients are needed to evaluate and clarify this issue.

// Kai-Xiong Liu 1, 2, 3 , Qin Chen 4 , Gong-Ping Chen 1, 2, 3 , Jian-Chai Huang 1, 2, 3 , Jie-Feng Huang 1, 2, 3 , Xin-Ru He 1, 2, 3 , Ting Lin 1, 2, 3 and Qi-Chang Lin 1, 2, 3 1 Department of Respiratory Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China 2 Laboratory of Respiratory Disease of Fujian Medical University, Fuzhou 350005, China 3 Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou 350005, China 4 Integrated Chinese and Western Medicine Colleges, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China Correspondence to: Qi-Chang Lin, email: chang4e@126.com Keywords: chronic intermittent hypoxia (CIH); obstructive sleep apnea (OSA); autophagy; Beclin-1; miR-30a Received: August 21, 2017 Accepted: September 03, 2017 Published: January 02, 2018 ABSTRACT Chronic intermittent hypoxia (CIH) in obstructive sleep apnea causes damages of aortic endothelial cells, which predisposes development of many cardiovascular diseases. Recently, both altered expression of microRNAs (miRNAs) and impaired autophagy were found to be associated with endothelial cell dysfunction in CIH. However, the exact molecular regulatory pathway has not been determined. Here, we addressed this question. In a mouse model of CIH, we detected significant upregulation of miR-30a, a miRNA that targets 3′-UTR of autophagy-associated protein 6 (Beclin-1) mRNA to suppress the protein translation, which subsequently attenuated the endothelial cell autophagy against cell death. Indeed, unlike Beclin-1 mRNA, the Beclin-1 protein in endothelial cells did not increase after CIH. Suppression of miR-30a by expression of antisense of miR-30a significantly increased Beclin-1 levels to enhance endothelial cell autophagy in vitro and in vivo , which improved endothelial cell survival against CIH. Together, these data suggest that endothelial cell autophagy in CIH may be attenuated by miR-30a-mediated translational control of Beclin-1, as an important cause of endothelial cell dysfunction and damage.

Objective Obstructive sleep apnea (OSA) has been recognized as being associated with low level of insulin growth factor-1 (IGF-1). However, the impact of OSA treatment using continuous positive airway pressure (CPAP) on IGF-1 remains controversial. We performed a meta-analysis to determine whether effective CPAP therapy could increase IGF-1 levels. Design Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before September 2014. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum IGF-1 was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy. Results Six articles with 168 patients were included in this meta-analysis, including five observational studies and one randomized controlled study. The meta-analysis showed that CPAP was associated with a statistically significant increase in IGF-1 in OSA patients (SMD=−0.436, 95% confidence interval=−0.653 to −0.218, P =0.000). Conclusions This meta-analysis suggested that CPAP therapy was associated with an increase in IGF-1 in patients with OSA. Further large-scale, well-designed interventional investigations are needed to clarify this issue.

Background Excessive daytime sleepiness (EDS), which is commonly considered a cardinal sign of obstructive sleep apnea (OSA), may lead to an increased rate of metabolic syndrome (MetS), and be an independent risk factor for cardiovascular morbidity and mortality. The aim of this cross-sectional study was to examine the role of EDS in MetS and its components by researching severe OSA patients. Methods The records of 175 consecutive patients who underwent standard polysomnography and diagnosed severe OSA were included. Subjective daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). Fasting glucose, lipids, insulin and polysomnography parameters were measured. A metabolic score was counted as the total number of the positive diagnostic criteria of MetS for each subject, which indicated the level of metabolic disorder. Results The prevalence of central obesity, hypertriglyceridemia, low high density lipoprotein-cholesterol and MetS (78.2% vs 28.6%) was significantly higher among EDS group compared with control group. Compared with non-EDS patients, patients with EDS showed significantly higher metabolic score (3.22 ± 0.94 vs 1.96 ± 1.06). After adjustment for confounders, ESS score, log insulin and age significantly predicted the metabolic score (β = 0.567, P = 0.000; β = 0.197, P = 0.001 and β = 0.118, P = 0.048, respectively). Conclusion EDS was independently correlated with the sum of metabolic components in severe OSA patients. Our study suggested that EDS might be a potentially useful clinical marker to identify patients with severe OSA at risk of MetS.

Purpose Obstructive sleep apnea (OSA) is suggested as a potential risk factor of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is still far from clear. The aim of this observational study was to investigate the influence of OSA-related hypoxia on severity of liver injury in patients with NAFLD. Methods Consecutive patients with ultrasound-diagnosed NAFLD who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Subjects were divided into control, moderate, and severe groups. Results A total of 85 subjects with 73 males and 12 females were included (mean age, 44.67 ± 1.28 years; mean body mass index, 27.28 ± 0.33 kg/m2). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, gamma glutamyltransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose, and high-sensitivity C-reactive protein significantly increased with the aggravation of OSA. In multivariate analysis, oxygen desaturation index was the major contributing factor for elevated ALT (β = 0.435, p = 0.000), average O2 saturation was the major independent predictor of elevated AST (β = −0.269, p = 0.020). Conclusions OSA-related hypoxia was independently associated with the biochemical evidence of liver injury in the presence of NAFLD.

BACKGROUND: The purpose of this observational study was to investigate the relationship between upper-airway configuration assessed by CT imaging during the Muller maneuver state and the severity of obstructive sleep apnea syndrome (OSAS). METHODS: A total of 358 snoring subjects who underwent standard polysomnography and upper-airway configuration by using CT imaging were enrolled. According to the apnea-hypopnea index (AHI), subjects were classified into 4 groups: snoring group (simple snoring), AHI < 5; mild OSAS, 5 ≤ AHI < 15; moderate OSAS, 15 ≤ AHI < 30; and severe OSAS, AHI ≥ 30. We also divided the upper airway into 3 parts, named the nasopharynx, oropharynx, and hypopharynx, from the CT scan and evaluated the minimal cross-sectional area (mCSA) and the shape of each airway level and calculated upper-airway length and distance from mandibular plane to hyoid bone (MPH). RESULTS: Multivariate logistic stepwise regression analysis identified body mass index (BMI), mCSA of nasopharynx, upper-airway length, and MPH as risk factors for the severity of OSAS. When subdivided for BMI and sex, upper-airway length was a risk factor for OSAS in non-obese (BMI < 27 kg/m2) and male subjects, and MPH was a risk factor only in obese (BMI ≥ 27 kg/m2) subjects. Meanwhile, mCSA of nasopharynx was significantly associated with the severity of OSAS independent of BMI. CONCLUSIONS: Subjects with severe OSAS have more significant abnormalities of the upper airway. Obesity, mCSA of nasopharynx, upper-airway length, and MPH may contribute to the severity of OSAS. Obesity and sex should be taken into account when evaluating the abnormalities of upper-airway anatomy in snorers and patients with OSAS.

The aim of this observational study was to investigate the influence of continuous positive airway pressure (CPAP) on arterial blood gas and venous lactate, markers of tissue hypoxia, among obstructive sleep apnea syndrome (OSAS) patients, and determine the risk factor of serum lactate and hydrogen ion concentration (PH) in OSAS patients. One-hundred and nine patients with newly diagnosed OSAS were enrolled in the study. All individuals were treated with CPAP for one night. Venous lactate and arterial blood gas were gathered from all subjects in the morning at the end of polysomnography and the next morning after CPAP treatment. Of the 109 selected subjects, the average lactate level was 2.23 ± 0.59 mmol/L, and the mean PH, PaO2, and PaCO2 were 7.380 ± 0.23, 88.14 ± 17.83 mmHg, and 38.70 ± 4.28 mmHg, respectively. Compared to baseline, lactic acid significantly decreased (2.10 ± 0.50 mmol/L, p = 0.03), while PH increased (7.388 ± 0.27, p

Obstructive sleep apnea (OSA) is closely related to nonalcoholic fatty liver disease (NAFLD), though the mechanism is not conclusive as obesity is a confounder. The objective of this observational study was to investigate the correlation between these disorders in nonobese subjects. We consecutively enrolled nonobese individuals undergoing polysomnography and abdominal ultrasonography and analyzed differences in NAFLD patients grouped by the apnea–hypopnea index (AHI) and in OSA patients according to the presence or absence of NAFLD. Multivariate regression analysis was used to evaluate the independent risks of NAFLD in OSA patients. A total of 175 participants were included. The 106 ultrasound-diagnosed NAFLD patients were classified into four groups by AHI. There were no significant differences in triglycerides (TG), serum aminotransferase levels of alanine aminotransferase and aspartate aminotransferase, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance (HOMA-IR) with worsening OSA. In both OSA patients with NAFLD and those without NAFLD, body mass index (BMI), the lowest oxygen saturation (LaSO2), HOMA-IR, and TG were significantly associated. Additionally, BMI, LaSO2, and TG independently predicted the development of NAFLD after adjustments (odds ratio [OR] = 1.562, p = 0.003; OR = 0.960, p = 0.03; OR = 3.410, p

The purpose of this study was to evaluate the clinical and radiologic results of a consecutive series of Wagner SL arthroplasties in patients with unstable intertrochanteric osteoporotic fractures. Forty-seven consecutive arthroplasties for unstable intertrochanteric fractures using Wagner SL hip stems were studied. All patients had bone mineral density less than − 2.5 SD. At average follow-up of 2.7 years, mean Harris Hip Scores were 89.4 (range, 65–100) and 87.7 (range, 57–100) for total hip arthroplasties and hemiarthroplasties, respectively. Twenty-one patients (53.8%) had excellent Harris Hip Scores (> 90, 14 [35.9%]). Evidence of clinical and radiologic healing was first noted at a mean follow-up of 3.7 months (3–5 months). Wagner SL hip arthroplasties for unstable intertrochanteric osteoporotic fractures have favourable short-term clinical and radiological outcomes.

The purpose of this study was to determine the safety and effectiveness, as assessed by risk of bleeding and incidence of deep venous thrombosis (DVT), of administering delayed low-molecular-weight heparin (LMWH) after total knee arthroplasty. A prospective study of 210 consecutive patients undergoing primary unilateral total knee arthroplasty was undertaken. The patients were randomized into two groups: one of which was managed according to a standard LMWH program (LMWH-s group) and the other with delayed LMWH (LMWH-p). LMWH was initiated 12 h after wound closure in the LMWH-s group, and 24 h after wound closure in the LMWH-p group. The total blood loss in the first three postoperative days was calculated and all complications were recorded. The mean total blood loss was 435 and 387 mL in the LMWH-s group and LMWH-p group, respectively (p