Comparison of 14 respiratory pathogens among hospitalized children during and after the COVID-19 outbreak in Chaoshan area.

BACKGROUND: Since January 2020, measures has been adopted in the Chaoshan area to limit the spread of COVID-19. Restrictions were removed after August 2020. At the same time, children returned to school. We previously reported the changes of 14 main respiratory pathogens in hospitalized children before and during the COVID-19 outbreak in Chaoshan area. However, the changes of respiratory pathogen spectrum in hospitalized children after the epidemic are still unknown, which will be elucidated in this study. METHODS: There are 6201 children hospitalized with respiratory tract infection were enrolled in the study, which were divided into two groups: 2533 from outbreak group (1 January 2020-31 December 2020), and 3668 from post-outbreak group (1 January 2021-31 December 2021). Pharyngeal swab samples were collected. 14 respiratory tract pathogens were detected by liquid chip technology. RESULTS: The positive rate of pathogen detection is significantly lower in the outbreak group (65.42%, 1657/2533) than that in the post-outbreak group (70.39%, 2582/3668; χ2 = 17.15, P < 0.05). The Influenza A virus (FluA) detection rate was 1.9% (49) in 2020, but 0% (0) in 2021. The detection rates of Bordetella pertussis (BP) decreased from 1.4% (35) in 2020 to 0.5% (17) in 2021. In contrast, the detection rates of  Influenza B virus (FluB), Cytomegalovirus (CMV), Haemophilus influenzae (HI), Streptococcus pneumoniae (SP) increased from 0.3% (8), 24.7% (626), 2.0% (50) and 19.4% (491) in 2020 to 3.3% (121), 27.9% (1025), 4.6% (169), 22.8% (836) in 2021, respectively (P < 0.01). CONCLUSIONS: The detection rates of pathogens such as FluA, FluB, CMV, HI, SP, BP were statistically different between 2020 and 2021. From 2020 to 2021, the positive rates of Flu, CMV, HI and SP increased, while the positive rates of FluA and BP decreased. After the COVID-19 prevention and control measures are gradually relaxed, the positive rate of respiratory pathogens in children aged from 6 months to 6 years will increase.

Diagnostic consistency between admission and discharge of pediatric cases in a tertiary teaching hospital in China.

BACKGROUND: Patient-centered, high-quality health care relies on accurate and timely diagnosis. Diagnosis is a complex, error-prone process. Prevention of errors involves understanding the cause of errors. This study investigated diagnostic discordance between admission and discharge in pediatric cases. METHODS: We retrospectively reviewed the electronic medical records of 5381 pediatric inpatients during 2017-2018 in a tertiary teaching hospital. We analyzed diagnostic consistency by comparing the first 4 digits of admission and discharge ICD-10 codes of the cases and classified them as concordant for "complete and partial match" or discordant for "no match". RESULTS: Diagnostic discordance was observed in 49.2% with the highest prevalence in infections of the nervous and respiratory systems (Ps < 0.001). Multiple (multivariable) logistic regression analysis predicted a lower risk of diagnostic discordance with older children (aOR, 95%CI: 0.94, 0.93-0.96) and a higher risk with infectious diseases (aOR, 95%CI: 1.49, 1.33-1.66) and admission by resident and attending pediatricians (aOR, 95%CI: 1.41, 1.30-1.54). Discordant cases had a higher rate of antibiotic prescription (OR, 95%CI: 2.09, 1.87-2.33), a longer duration of antibiotic use (P = 0.02), a longer length of hospital stay (P < 0.001), and higher medical expenses (P < 0.001). CONCLUSIONS: This study denotes a considerably high rate of discordance between admission and discharge diagnoses with an associated higher and longer prescription of antibiotics, a longer length of stay, and higher medical expenses among Chinese pediatric inpatient cases. Infectious diseases were identified as high-risk clinical conditions for discordance. Considering potential diagnostic and coding errors, departmental investigation of preventable diagnostic discordance is suggested for quality health care and preventing potential medicolegal consequences.

Linguistic barriers and healthcare in China: Chaoshan vs. Mandarin.

BACKGROUND: China has 129 dialects with Mandarin as the standard and Chaoshan as the major dialect of the Chaoshan region in Guangdong. This study aimed to describe the dialect competence and usage, communication difficulty, impact of linguistic barriers, and subjective experience in healthcare. METHODS: Healthcare providers (n = 234) and healthcare consumers (n = 483) at two tertiary teaching hospitals in Shantou, Chaoshan region participated in an anonymous survey. RESULTS: Chaoshan and Mandarin were spoken respectively by ca. 80% and 6.1% of the participants. Monolinguals accounted for 28.5%, including 16.8% of Chaoshan-speaking healthcare providers and 18% of Mandarin-speaking healthcare consumers. The monolinguals preferentially used their competent dialect (Ps < 0.001) and had significant communication difficulties (Ps < 0.0001), with the mean (SD) score of 3.06 (0.96) out of 4 with Mandarin for healthcare providers and 2.18 (1.78) and 1.64 (1.40) with Mandarin and Chaoshan, respectively, for healthcare consumers. The monolingual healthcare providers perceived significant negative impacts of linguistic barriers on the entire healthcare delivery process (Ps < 0.0001). Regression analyses showed the length of stay in the Chaoshan region as a protective factor of linguistic barrier with a limited protective effect. CONCLUSIONS: This is the first report of significant linguistic barriers in healthcare imposed by Mandarin and Chaoshan dialects in Chaoshan, China. With perceived adverse impacts on the entire healthcare delivery and risks to the healthcare quality and burden, interventions such as professional interpreter service, service-learning interpreter program, or mobile interpreting apps that are medically accurate and culturally sensitive are suggested for dialectally diverse China.

Online health information-seeking behaviors and skills of Chinese college students.

BACKGROUND: Seeking online health information (OHI) has become a common practice globally. The information seekers could face health risks if they are not proficient in OHI literacy. The OHI-seeking behaviors and skills of Chinese college students, the largest proportion of college students in the world, are understudied. This study was aimed to describe OHI-seeking behaviors and skills of college students in Guangdong, China. METHODS: College students in the Guangdong province with OHI-seeking experience were invited via WeChat, QQ, and Sina Weibo using QR code posters and flyers for participation in this online anonymized questionnaire-based study. Data on demographics, OHI literacy, information resources, search approaches, and behaviors were collected. The relationship between perceived OHI literacy and high-risk behaviors was investigated by bivariate logistic regression analysis. RESULTS: Respondents were 1203 college students with a mean age of 20.6 years, females (60.2%), and undergraduates (97.2%). They sought health information via websites (20.3%), WeChat (2.6%), or both (77.1%). Baidu was the main search engine, and baike.baidu.com (80.3%), Zhihu.com (48.4%), and Zhidao.baidu.com (35.8%) were top three among 20 searched websites for information about self-care (80.7%), general health (79.5%), disease prevention (77.7%), self-medication (61.2%), family treatment (40.9%), drugs (37.7%), western medications (26.6%), hospitals (22.7%), physicians (21.4%), and Traditional Chinese Medicine (15.6%). Despite most respondents (78%) lacked confidence in the evidence quality and satisfaction with the results, only 32.4% further consulted doctors. Many (> 50%) would recommend the retrieved information to others. About 20% experienced hacking/Internet fraud. Cronbach's alpha for the internal consistency of OHI literacy was 0.786. Bivariate logistic regression analysis showed that students who believed they can judge the evidence level of OHI were more likely to self-diagnose (OR = 2.2, 95%CI, 1.6-3.1) and look for drug usage (OR = 3.1, 95%CI, 1.9-5.0). CONCLUSIONS: This study reveals Chinese college students' heavy reliance on OHI to manage their own and others' health without sufficient knowledge/skills to identify misinformation and disinformation. The apparent risky information-seeking behaviors of Chinese college students warrant the provision of regulated, accurate, and actionable health information; assurance of cybersecurity; and health information literacy promotion in colleges by concerned authorities.

Basic Fibroblast Growth Factor Influences Epidermal Homeostasis of Living Skin Equivalents through Affecting Fibroblast Phenotypes and Functions.

AIMS: To elucidate the possible mechanisms of how basic fibroblast growth factor (bFGF) influences epidermal homeostasis in a living skin equivalent (LSE) model. METHODS: Several wound healing-related growth factors were analyzed at protein and mRNA levels for dermal fibroblasts of induced alpha-smooth muscle actin (α-SMA)-positive or α-SMA-negative phenotypes. During culturing an LSE model by seeding normal human keratinocytes on a fibroblast-populated type I collagen gel, bFGF or neutralizing antibody for keratinocyte growth factor (KGF) was added to investigate its effects on fibroblast phenotypes and, subsequently, epidermal homeostasis by histology and immunohistochemistry. RESULTS: The α-SMA-positive phenotype of fibroblasts induced by transforming growth factor beta-1 (TGF-ß1) markedly suppressed the expression of KGF and hepatocyte growth factor (HGF), and slightly upregulated vascular endothelial growth factor (VEGF) and TGF-ß1 at mRNA and protein levels, compared with α-SMA-negative fibroblasts treated with bFGF. α-SMA expression of fibroblasts at the epidermal-mesenchymal junction of the LSEs was suppressed by the addition of bFGF, and a better-differentiated epidermis was presented. The abrogation of KGF from fibroblasts by the addition of the KGF neutralizing antibody disenabled the LSE culturing system to develop an epidermis. CONCLUSIONS: bFGF, through affecting the phenotypes and functions of fibroblasts, especially KGF expression, influenced epidermal homeostasis in an LSE model.

Hand-foot-mouth disease and use of steroids, intravenous immunoglobulin, and traditional Chinese herbs in a tertiary hospital in Shantou, China.

BACKGROUND: In contrast to the guidelines of World Health Organization (WHO) and United States-Centers for Disease Control and prevention (US-CDC), the Chinese national guidelines recommend the use of steroids, intravenous immunoglobulin (IVIG), or traditional Chinese herbs (TCHs) in hand-foot-mouth disease (HFMD) management. Their use and therapeutic efficacies are, however, unclear. We aimed to describe their use in and the clinical outcomes of hospitalized HFMD cases. METHODS: A retrospective review of hospital medical records for HFMD cases during 2008-2016 was conducted in a medical school-affiliated tertiary hospital in Shantou, Guangdong, China. RESULTS: Hospitalized children with the discharge diagnosis of HFMD (n = 3778), comprising mild (58.4%), severe (41.5%), and very severe (0.1%) cases, were enrolled in the study. Steroids, IVIG, and antiviral TCH Lan-Qin were respectively prescribed in 60.5, 37.1, and 71.0% of cases. Most cases (99.8%) recovered and six died. Recovery rate was lower with the use of IVIG and higher with Lan-Qin (alone or in combination with steroid) in the mild cases (Ps < 0.05). Longer hospital stay was observed with steroid/IVIG with or without Lan-Qin in the severe cases (Ps < 0.05). CONCLUSIONS: This nine-year retrospective review shows 1) an increase in the incidence of HFMD as well as the use of steroids, IVIG, and TCH over time, 2) no significant advantage of using steroids and IVIG, either alone or in combination, in the management of mild HFMD cases, and 3) a higher recovery rate in mild HFMD cases with the use of antiviral TCH (Lan-Qin). Our findings need verification in a larger prospect study with cases from hospitals in other regions of China. Lan-Qin efficacy should be evaluated in randomized trials. Meanwhile, caution should be exercised in the extensive use of steroids and IVIG in HFMD management.

Viral aetiology of acute respiratory infections among children and associated meteorological factors in southern China.

BACKGROUND: Acute respiratory infections (ARIs) are common in children and mostly caused by viruses, but the significance of the detection of multiple viruses in ARIs is unclear. This study investigated 14 respiratory viruses in ARIs among children and associated meteorological factors in Shantou, southern China. METHODS: Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses--influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV)--by multiplex real-time PCR. RESULTS: We identified at least one virus in 82.3% (884/1,074) and multiple viruses in 38.6% (415/1,074) of patients. EV and HRV were the most frequently detected single viruses (42.3%, 374/884 and 39.9%, 353/884 respectively) and co-detected pair (23.1%, 96/415). Overlapping seasonal trends of viruses were recorded over the year, with dual peaks for EV and single peaks for the others. By logistic regression analysis, EV was positively associated with the average temperature and humidity, hCoV, and PIV4, but negatively with HRV, PIV3, and hBoV. HRV was inversely associated with EV and PIV3. CONCLUSIONS: This study reports high viral detection and co-detection rates in pediatric ARI cases mainly due to EV and HRV. Many viruses circulated throughout the year with similar seasonal trends in association with temperature, humidity, and wind velocity. Statistically significant associations were present among the viruses. Understanding the polyviral etiology and viral interactions in the cases with multiple viruses warrants further studies.

Recent advances of biocompatible optical nanobiosensors in liquid biopsy: towards early non-invasive diagnosis.

Liquid biopsy is a non-invasive diagnostic method that can reduce the risk of complications and offers exceptional benefits in the dynamic monitoring and acquisition of heterogeneous cell population information. Optical nanomaterials with excellent light absorption, luminescence, and photoelectrochemical properties have accelerated the development of liquid biopsy technologies. Owing to the unique size effect of optical nanomaterials, their improved optical properties enable them to exhibit good sensitivity and specificity for mitigating signal interference from various molecules in body fluids. Nanomaterials with biocompatible and optical sensing properties play a crucial role in advancing the maturity and diversification of liquid biopsy technologies. This article offers a comprehensive review of recent advanced liquid biopsy technologies that utilize novel biocompatible optical nanomaterials, including fluorescence, colorimetric, photoelectrochemical, and Raman broad-spectrum-based biosensors. We focused on liquid biopsy for the most significant early biomarkers in clinical medicine, and specifically reviewed reports on the effectiveness of optical nanosensing technology in the detection of real patient samples, which may provide basic evidence for the transition of optical nanosensing technology from engineering design to clinical practice. Furthermore, we introduced the integration of optical nanosensing-based liquid biopsy with modern devices, such as smartphones, to demonstrate the potential of the technology in portable clinical diagnosis.

An analysis of neutrophil-to-lymphocyte ratios and monocyte-to-lymphocyte ratios with six-month prognosis after cerebral contusions.

Background and purpose: Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with six-month outcomes. Methods: Retrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR. Results: A total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively. Conclusion: NLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings.

Induction of cytopathic effect and cytokines in coxsackievirus B3-infected murine astrocytes.

BACKGROUND: Coxsackievirus commonly infects children and occasionally causes severe meningitis and/or encephalitis in the newborn. The underlying mechanism(s) behind the central nervous system pathology is poorly defined. METHODS: It is hypothesized that astrocytes may be involved in inflammatory response induced by CVB3 infection. Here we discuss this hypothesis in the context of CVB3 infection and associated inflammatory response in primary mouse astrocytes. RESULTS: The results showed that coxsackievirus receptor (CAR) was distributed homogeneously on the astrocytes, and that CVB3 could infect and replicate in astrocytes, with release of infectious virus particles. CVB3 induced cytopathic effect and production of proinflammatory cytokines IL-1ß, TNF-α, IL-6, and chemokine CXCL10 from astrocytes. CONCLUSION: These data suggest that direct astrocyte damage and cytokines induction could be a mechanism of virus-induced meningitis and/or encephalitis.

Self-driven immune checkpoint blockade and spatiotemporal-sensitive immune response monitoring in acute myeloid leukemia using an all-in-one turn-on bionanoprobe.

Immune checkpoint (ICP) blockade (ICB) is one of the most promising immunotherapies for acute myeloid leukemia (AML). However, owing to their heterogeneity, AML cells may cause uncoordinated metabolic fluxes and heterogeneous immune responses, inducing the release of a spatiotemporally sensitive immune response marker. Timely and in situ detection of immune responses in ICB therapy is important for therapeutic strategy adjustment. Herein, we constructed an all-in-one nanoprobe for self-driving ICB and simultaneously detecting an immune response in the same AML cell in vivo, thus enabling accurate evaluation of heterogenetic immune responses in living AML mice without additional drug treatment or probe processes. The nature-inspire polydopamine (PDA) nanoparticles loaded with an ICP blocker were targeted to the leukocyte immunoglobulin like receptor B4 (a new ICP) of AML cells to induce the release of immune response marker granzyme B (GrB). The PDA nanoparticles were additionally paired with carbon-derived graphene quantum dots (GQDs) to construct a full-organic 'turn-on' bionanoprobe that can transfer fluorescence resonance energy for GrB detection. This multifunctional nanoprobe was validated for triggering ICB therapy and monitoring the changes of GrB levels in real-time both in vitro and in vivo. The organic nanoprobe showed excellent permeability and retention in tumor cells and high biocompatibility in vivo. This bionanoprobe orderly interacted with the upstream ICP molecules and downstream signal molecule GrB, thereby achieving in situ immune response signals within the therapeutic efficacy evaluation window.

Health literacy and risk of viral hepatitis among Chinese school children.

INTRODUCTION: Poor literacy is associated with hepatitis morbidity and mortality. Adolescents are especially at risk of hepatitis C. This study investigated viral hepatitis literacy, risk, and influencing factors among Chinese middle and high school students. METHODOLOGY: A supervised self-administered survey was conducted with school children from six schools in Shantou, China. Data on demographics, health literacy, and risk of viral hepatitis were analyzed. RESULTS: A total of 1732 students (from three middle and three high schools) participated in the study. Their major information resources were the internet (39.5%, 685/1732), television (28.8%, 498/1732), family (27.7%, 479/1732), and school (21.2%, 368/1732). The mean literacy score on the manifestations and risk factors of hepatitis was 3.4 ± 2.2 and 4.0 ± 2.3 (out of 8), respectively. Multiple linear regression models showed being female and in high school, having parents with higher education levels, and school or clinicians as an information resource were independent positive predictors, whereas poor awareness of risk factors was a negative predictor for health literacy. CONCLUSIONS: We report the risk of hepatitis among Chinese middle and high school students due to limited literacy and poor attitudes towards health-risk behaviors. Health education in school is recommended for preventable health risks among Chinese adolescents.

COVID-19 epidemic and Chinese medical students: perception, emotions, attitudes, and conformity during domicile quarantine.

INTRODUCTION: Students from Shantou University Medical College were subject to domicile quarantine during the early phase of the COVID-19 outbreak. METHODOLOGY: We investigated their experience during March-April 2020 using a cross-sectional, self-administered, anonymous online survey. RESULTS: Out of 531 respondents, 75.7% became aware of the outbreak via the Internet (61.7%), WeChat (57.8%), and Weibo (49%). Nearly all students knew COVID-19 manifestations, incubation period, and transmission modes; about half considered wearing facemask and hand hygiene as effective epidemic interventions. They experienced various emotional reactions that changed significantly in response to the outbreak, lockdown, and quarantine (ps < 0.001), with depression in 23.3%. Most students (83.4%-99.4%) had positive attitudes and good compliance towards domicile quarantine and preventive measures. Females were significantly better than males in hand hygiene compliance (p = 0.04). More students with positive attitudes and good compliance than those without educated their families (ps < 0.05 - ps < 0.001). Multiple logistic regression showed negative relationships between anger and hand hygiene attitude (OR = 0.06, 95% CI = 0.01-0.87); confusion and quarantine compliance (0.30, 0.12-0.76); and anger and compliance with quarantine (0.32, 0.11-0.93), facemask (0.12, 0.03-0.50), and hand hygiene (0.27, 0.08-0.88). CONCLUSIONS: This study revealed how multichannel risk communication, early awareness, positive attitudes, and conformity of medical college students might have contributed to the favorable outcome from the COVID-19 epidemic in China. Clear, accurate, consistent, early risk communication by the local, national, and international public health authorities seems critical to promote public understanding, correct risk perception, and rational emotions and attitudes, leading to optimal conformity.

Determining the Prognostic Value of Spliceosome-Related Genes in Hepatocellular Carcinoma Patients.

Background: The spliceosome plays an important role in mRNA alternative splicing and is aberrantly expressed in several tumors. However, the potential roles of spliceosome-related genes in the progression of hepatocellular carcinoma (HCC) remain poorly understood. Materials and Methods: Patient data were acquired from public databases. Expression differences and survival analyses were used to assess the importance of spliceosome-related genes in HCC prognosis. To explore the potential regulatory mechanisms of these genes, a protein-protein interaction network was constructed and screened using univariate and multivariate Cox regression and random forest analyses. This was used to create a five-gene prognostic model. The prognostic value and predictive power of the five-gene signature were assessed using the Kaplan-Meier and time-dependent receiver operating characteristic analyses in the training set. These results were further validated in an independent external set. To facilitate clinical application, a nomogram was prepared to predict the overall survival of HCC patients. The relative expression of five genes was detected using real-time quantitative polymerase chain reaction. Results: The analysis revealed that LSM1-7, SNRPB, SNRPD1-3, SNRPE, SNRPF, SNRPG, and SNRPN could be used as prognostic biomarkers in HCC patients. Moreover, the five-gene risk model could clearly distinguish between the high-and low-risk groups. Furthermore, the risk model was associated with the tumor mutation burden, immune cell infiltration of CD8+ T cells, natural killer T cells, M2 macrophages, and immune checkpoint inhibitors, which also demonstrated the predictive efficacy of this risk model in HCC immunotherapy. Conclusion: Spliceosome-related genes and the five-gene signature could serve as novel prognostic biomarkers for HCC patients, aiding clinical patient monitoring and follow-up.

The Prognostic Significance and Potential Mechanism of Ferroptosis-Related Genes in Hepatocellular Carcinoma.

Ferroptosis exerts a pivotal role in the formation and dissemination processes of hepatocellular carcinoma (HCC). The heterogeneity of ferroptosis and the link between ferroptosis and immune responses have remained elusive. Based on ferroptosis-related genes (FRGs) and HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) cohorts, we comprehensively explored the heterogeneous ferroptosis subtypes. The genetic alterations, consensus clustering and survival analysis, immune infiltration, pathway enrichment analysis, integrated signature development, and nomogram building were further investigated. Kaplan-Meier plotter confirmed statistically differential probabilities of survival among the three subclusters. Immune infiltration analysis showed there were clear differences among the types of immune cell infiltration, the expression of PD-L1, and the distribution of TP53 mutations among the three clusters. Univariate Cox regression analysis, random survival forest, and multivariate Cox analysis were used to identify the prognostic integrated signature, including MED8, PIGU, PPM1G, RAN, and SNRPB. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves revealed the satisfactory predictive potential of the five-gene model. Subsequently, a nomogram was established, which combined the signature with clinical factors. The nomogram including the ferroptosis-based signature was conducted and showed some clinical net benefits. These results facilitated an understanding of ferroptosis and immune responses for HCC.

Heterologous SH3-p85beta inhibits influenza A virus replication.

Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway can support the replication of influenza A virus through binding of viral NS1 protein to the Src homology 3 (SH3) domain of p85beta regulatory subunit of PI3K. Here we investigated the effect of heterologously overexpressed SH3 on the replication of different influenza A virus subtypes/strains, and on the phosphorylation of Akt in the virus-infected cells. We found that heterologous SH3 reduced replication of influenza A viruses at varying degrees in a subtype/strain-dependent manner and SH3 overexpression reduced the induction of the phosphorylation of Akt in the cells infected with PR8(H1N1) and ST364(H3N2), but not with ST1233(H1N1), Ph2246(H9N2), and Qa199(H9N2). Our results suggest that interference with the NS1-p85beta interaction by heterologous SH3 can be served as a useful antiviral strategy against influenza A virus infection.

Blood microRNA 202-3p associates with the risk of essential hypertension by targeting soluble ST2.

MicroRNA (miR)-202-3p has attracted a great deal of attention in the fields of oncology, gynecology, and metabolic disorders. However, its role in cardiovascular diseases remains to be clarified. We previously found that disruption of miR-202-3p mediated regulation of expression of soluble (s)ST2, a decoy receptor for interleukin (IL)-33, promotes essential hypertension (EH). In the present study, we first measured miR-202-3p expression levels in the blood of 182 EH cases and 159 healthy controls using TaqMan assays. miR-202-3p levels were shown to be significantly higher in EH cases than controls (fold change = 3.58, P<0.001). Logistic regression analysis revealed that higher miR-202-3p expression was associated with an increased occurrence of EH (adjusted odds ratio (OR): 1.57; 95% confidence interval (CI), 1.36-1.82; P<0.001). Addition of miR-202-3p to traditional risk factors showed an additive prediction value for EH. Further functional experiments indicated that miR-202-3p could be induced by angiotensin II (Ang II) and inhibited by Ang II-triggered soluble ST2 (sST2) expression in a negative feedback manner. Moreover, blood miR-202-3p levels were negatively correlated with sST2 expression in vivo. Our study shows that blood miR-202-3p levels were significantly associated with the occurrence of EH. These findings indicate that miR-202-3p exerts a protective role against EH by antagonizing the induction of sST2 by Ang II.

COVID-19 outbreak prevention by early containment in Shantou, China.

INTRODUCTION: To report about the successful outbreak containment of COVID-19 in Shantou, one of the prefectural cities of Guangdong province in the mainland China. METHODOLOGY: All patients confirmed as having COVID-19 between 23 January and 25 March 2020 by RT-PCR assay in the clinical lab of Shantou CDC were included and divided into three groups based on the source of identification: hospital diagnosis, contact tracing, and community screening. Collected data was analyzed and compared among these three groups. RESULTS: A total of 25 COVID-19 cases were identified in Shantou. The first case was identified on 14 January 2020 at one of two COVID-19 dedicated hospitals in Shantou. The majority of the cases were either imported from Wuhan or linked to Wuhan/Hubei. The median lag time for diagnosis (i.e., the time between symptom onset and case confirmation) was 2 days (IQR, 2.0-4.0) for all cases, 9 days (IQR, 7.0-10.0) for the cases diagnosed in hospitals, 2 days (IQR, 1.5-2.0) for the cases in contact tracing, and 4 days (IQR, 2.5-4.5) for cases in community screening, with a significantly longer diagnosis lag time in hospitals (p = 0.003). Multivariate linear regression models showed larger family size and severe cases as the significant predictor for increasing number of close contacts. CONCLUSIONS: The current pandemic appears to exist for an uncertain period. The early containment measures applied in Shantou, a city with insufficient healthcare resources for COVID-19, seems to be appropriate for cities or areas with similar profiles.

Differential suppressive effect of promyelocytic leukemia protein on the replication of different subtypes/strains of influenza A virus.

Promyelocytic leukemia protein (PML) plays an important role in the defense against a number of viruses, including influenza A virus. However, the sensitivity of influenza A virus subtypes/strains to PML is unknown. We investigated the role of PML in the replication of different influenza A virus subtypes/strains using pan-PML knock-down A549 cells and PML-VI-overexpressed MDCK cells. We found that (i) depletion of pan-PML by siRNA rendered A549 cells more susceptible to influenza A virus strains PR8(H1N1) and ST364(H3N2), but not to strains ST1233(H1N1), Qa199(H9N2) and Ph2246(H9N2); (ii) overexpression of PML-VI in MDCK cells conferred potent resistance to PR8(H1N1) infection, while lacked inhibitory activity to ST1233(H1N1), ST364(H3N2), Qa199(H9N2) and Ph2246(H9N2). Our results suggest that the antiviral effect of PML on influenza A viruses is viral subtype/strain specific.

Differential transcription-activating capability of NS1 proteins from different influenza virus subtypes expressed in yeast.

Influenza A virus NS1 protein is an important regulatory factor with multiple functions and contributes greatly to viral pathogenesis. In the present study, transcription-activating potential of NS1 from different influenza A virus subtypes was examined in yeast two-hybrid system. The bait vectors containing different NS1 genes, along with an empty prey vector, were transformed into yeast AH109(for growth assay on QDO plate and alpha-galactosidase assay), and Y187(for beta-galactosidase assay). AH109 transformants with NS1 gene from H1N1, H5N1, and H9N2 viruses grew vigorously on the QDO plate and secreted high level of alpha-galactosidase. Also, Y187 bearing the above NS1 genes exhibited enhanced beta-galactosidase activity. Nevertheless, H3N2-NS1-transformed AH109 and Y187 yeasts did not grow on QDO plate and secrete beta-galactosidase, respectively. These findings denote the remarkable variation in NS1 proteins from different influenza A virus subtypes on the transcription-stimulating capability in yeast.