A novel methionine metabolism-related signature predicts prognosis and immunotherapy response in lung adenocarcinoma.

Recent research revealed methionine metabolism as a key mediator of tumor initiation and immune evasion. However, the relationship between methionine metabolism and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unknown. Here, we comprehensively analyzed the genomic alterations, expression patterns, and prognostic values of 68 methionine-related regulators (MRGs) in LUAD. We found that most MRGs were highly prognostic based on 30 datasets including 5024 LUAD patients. Three distinct MRG modification patterns were identified, which showed significant differences in clinical outcomes and TME characteristics: The C2 subtype was characterized by higher immune score, while the C3 subtype had more malignant cells and worse survival. We developed a MethScore to measure the level of methionine metabolism in LUAD. MethScore was positively correlated with T-cell dysfunction and tumor-associated macrophages (TAMs), indicating a dysfunctional TME phenotype in the high MethScore group. In addition, two immunotherapy cohorts confirmed that patients with a lower MethScore exhibited significant clinical benefits. Our study highlights the important role of methionine metabolism in modeling the TME. Evaluating methionine modification patterns will enhance our understanding of TME characteristics and can guide more effective immunotherapy strategies.

Serum uric acid: A risk factor for right ventricular dysfunction and prognosis in heart failure with preserved ejection fraction.

Background: Hyperuricemia and right ventricular dysfunction (RVD) are both widespread in heart failure with preserved ejection fraction (HFpEF) patients. RVD is associated with a poor prognosis in HFpEF. The correlation between serum uric acid (UA) levels and right ventricular function is unclear. The prognostic performance of UA in patients with HFpEF needs further validation. Methods and results: A total of 210 patients with HFpEF were included in the study and divided into two groups according to UA level: the normal UA group (≤7 mg/dl) and the high UA group (>7 mg/dl). The variables examined included clinical characteristics, echocardiography, and serum biochemical parameters. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TAPSV). Baseline characteristics were compared between the two groups, and the correlation between baseline UA and RVD was assessed using multifactorial binary logistic regression. Kaplan-Meier curves were used to describe all-cause mortality and heart failure readmission. Results showed that right ventricular function parameters were worse in the high UA group. After adjusting for UA, left ventricular posterior wall thickness (LVPWT), N-terminal B-type natriuretic peptide (NT-proBNP), atrial fibrillation (AF), and low-density lipoprotein cholesterol (LDL-C), UA (odds ratio = 2.028; p < 0.001) was independently associated with RVD, and UA >7 mg/dl (HR = 2.98; p < 0.001) was associated with heart failure readmission in patients with HFpEF. Conclusion: Elevated serum UA is closely associated with RVD and significantly associated with the heart failure readmission rate in patients with HFpEF.

Secondhand smoking exposure and quality of life among pregnant and postnatal women: a network approach.

OBJECTIVE: This study examined the prevalence of exposure to secondhand smoke, its correlates and its association with quality of life (QOL) among pregnant and postnatal Chinese women. DESIGN: This was a multicentre, cross-sectional study. SETTING: Participants were consecutively recruited from eight tertiary hospitals located in eight municipalities or provinces in China. PARTICIPANTS: A total of 1140 women were invited to join this study and 992 (87.02%) completed all measures. PRIMARY AND SECONDARY OUTCOME: Measures women's secondhand smoking behaviour (frequency and location of exposure to secondhand smoking), and their QOL measured by the WHO Quality of Life Questionnaire. RESULTS: A total of 211 women (21.3%, 95% CI 18.7% to 23.8%) had been exposed to secondhand smoking. Exposure to secondhand smoking was most common in public areas (56.4%), and residential homes (20.5%), while workplaces had the lowest rate of exposure (13.7%). Women with physical comorbidities were more likely to report secondhand smoking exposure, while older women, women living in urban areas, those with college or higher education level, and women in their second trimester were less likely to report exposure to secondhand smoking. Network analysis revealed that there were six significant links between secondhand smoke and QOL items. The strongest negative edge was the connection between secondhand smoke and QOL9 ('physical environment health', edge weight=-0.060), while the strongest positive edge was the connection between secondhand smoke and QOL3 ('pain and discomfort', edge weight=0.037). CONCLUSION: The prevalence of exposure to secondhand smoking is becoming lower among pregnant and postnatal women in China compared with findings reported in previous studies. Legal legislation should be maintained and promptly enforced to establish smoke-free environments in both public and private urban/rural areas for protection of pregnant and postnatal women, especially those who are physically vulnerable and less educated.

Dimeric-(-)-epigallocatechin-3-gallate inhibits the proliferation of lung cancer cells by inhibiting the EGFR signaling pathway.

Non-small cell lung cancer (NSCLC) is one of the most general malignant tumors. The overexpression of epidermal growth factor receptor (EGFR) is a common marker in NSCLC, and it plays an important role in the proliferation, invasion, and metastasis of cancer cells. At present, drugs developed with EGFR as a target suffer from drug resistance, so it is necessary to study new compounds for the treatment of NSCLC. The active substance in green tea is EGCG, which has anti-cancer effects. In this study, we synthesized dimeric-(-)-epigallocatechin-3-gallate (prodelphinidin B-4-3,3‴-di-O-gallate, PBOG), and explored the effect of PBOG on lung cancer cells. PBOG can inhibit the proliferation and migration of NCI-H1975 cells, promote cell apoptosis, and inhibit cell cycle progression. In addition, PBOG can bind to the EGFR ectodomain protein and change the secondary structure of the protein. At the same time, PBOG decreases the expression of EGFR and downstream protein phosphorylation. Animal experiments confirmed that PBOG can inhibit tumor growth by inhibiting EGFR phosphorylation. Collectively, our study results show that PBOG may induce a decrease in intracellular phosphorylated EGFR expression by binding to the EGFR ectodomain protein, thereby inducing apoptosis and inhibiting cell cycle progression, thus providing a new strategy to treat lung cancer.

Short-term/long-term prognosis with or without beta-blockers in patients without heart failure and with preserved ejection fraction after acute myocardial infarction: a multicenter retrospective cohort study.

BACKGROUND: The role of beta-blockers in acute myocardial infarction patients without heart failure and with preserved left ventricular ejection fraction (LVEF ≥ 50%) is unknown. Our study aimed to retrospectively analyze the associations of beta-blockers on such patients. METHODS: This is a multicenter, retrospective study. After screening 5,332 acute myocardial infarction patients, a total of 2519 patients without heart failure and with LVEF ≥ 50% were included. The patients were divided into two groups: the prescribed (n = 2049) and unprescribed (n = 470) beta-blockers group. The propensity score inverse probability treatment weighting was used to control confounding factors. We analyzed the associations between beta-blockers and outcomes in the short-term (1-year) and long-term (median, 3.61 years). RESULTS: The primary outcome was all-cause mortality. The secondary outcomes were all-cause rehospitalization, cardiac death, recurrent myocardial infarction, new-onset heart failure rehospitalization. This study shows no statistically significant association between discharged with beta-blockers and all-cause mortality, either in the short-term [IPTW Adjusted, HR 1.02; 95%CI 0.43-2.40; P = 0.966] or long-term [IPTW Adjusted, HR 1.17; 95%CI 0.70-1.94; P = 0.547]. Discharged with beta-blockers was significantly associated with a reduced risk of short-term recurrent myocardial infarction [IPTW Adjusted, HR 0.44; 95%CI 0.20-0.97; P = 0.043], but there was no long-term relationship [IPTW Adjusted, HR 1.11; 95%CI 0.61-2.03; P = 0.735]. Other outcomes, such as new-onset heart failure rehospitalization and all-cause rehospitalization, were not observed with meaningful differences in either the short- or long-term. The results of sensitivity analysis were consistent with this. CONCLUSIONS: Beta-blockers might be associated with a reduced risk of recurrent myocardial infarction in patients without heart failure and with preserved left ventricular ejection fraction after acute myocardial infarction, in the short term. Beta-blockers might not be related to all-cause mortality in those patients, either in the short-term or long-term. Clinical trial registration Influence of Beta-blockers on Prognosis in Patients with Acute Myocardial Infarction Complicated with Normal Ejection Fraction, NCT04485988, Registered on 24/07/2020. Retrospectively registered.

The duration of beta-blocker therapy and outcomes in patients without heart failure or left ventricular systolic dysfunction after acute myocardial infarction: A multicenter prospective cohort study.

BACKGROUND: The duration of beta-blocker therapy in patients without heart failure (HF) or left ventricular systolic dysfunction after acute myocardial infarction (AMI) is unclear. HYPOTHESIS: Continuous beta-blocker therapy is associated with an improved prognosis. METHODS: This is a prospective, multicenter, cohort study. One thousand four hundred and eighty-three patients eventually met the inclusion criteria. The study groups included the continuous beta-blocker therapy group (lasted ≥6 months) and the discontinuous beta-blocker therapy group (consisting of the no-beta-blocker therapy group and the beta-blocker therapy <6 months group). The inverse probability treatment weighting was used to control confounding factors. The study tried to learn the role of continuous beta-blocker therapy on outcomes. The median duration of follow-up was 13.0 months. The primary outcomes were cardiac death and major adverse cardiovascular events (MACE). The secondary outcomes were all-cause death, stroke, unstable angina, rehospitalization for HF, and recurrent myocardial infarction (MI). RESULTS: Compared with discontinuous beta-blocker therapy, continuous beta-blocker therapy was associated with a reduced risk of unstable angina, recurrent MI, and MACE (hazard ratio [HR]: 0.51; 95% CI: 0.32-0.82; p = 0.006); but this association was not available for cardiac death (HR: 0.57; 95% CI: 0.24-1.36; p = 0.206). When compared to the subgroups of no-beta-blocker therapy and beta-blocker therapy <6 months, respectively, continuous beta-blocker therapy was still observed to be associated with a reduced risk of unstable angina, recurrent MI, and MACE. CONCLUSIONS: Continuous beta-blocker therapy was associated with a reduced risk of unstable angina or recurrent MI or MACE in patients without HF or left ventricular systolic dysfunction after AMI.

The experiences of people with type 2 diabetes in communicating with general practitioners in China - a primary care focus group study.

BACKGROUND: With the implementation of health care reforms in China, primary care is on a journey to provide care for most patients with type 2 diabetes. While Chinese general practitioners (GPs) have described challenges in communication with diabetes patients in their daily practice, little is known about patients' experiences in communicating with their GPs. METHODS: Five focus groups (of 4-5 participants each) were used to explore views from patients with type 2 diabetes. Purposive sampling was used to recruit a spread of participants from general practices in Guangzhou city, China. Focus groups were audio-recorded, transcribed, and thematically analyzed using the Framework Method. RESULTS: Ten males and 12 female patients from five general practices participated in focus group discussions, with a mean age of 57.3 years and 7.3 years of diabetes duration. Five main themes emerged: patients' understanding about diabetes, diabetes medication, communication with GPs, physician-patient relationships, and healthcare systems and context. Patients generally searched for information on the internet, but they weren't always sure if it was trustworthy. Several communication needs were described by diabetes patients, such as explanation of blood glucose monitoring, medication information support, communication in the risk of diabetes complications and cardiovascular disease, and language barriers. Communication was frequently brief and not tailored to their concerns, and some described being scolded or panicked by GPs. Participants acknowledged the pressures within the health system, such as short consultation times, an incoherent GP-hospital interface and high demand. CONCLUSIONS: Key issues from the patients' perspective for the development of primary care based management of diabetes in China were identified. People with type 2 diabetes require more access to trustworthy diabetes information and wish for better channels of communication with their GPs. Strategies may be required to improve GPs' communication skills with their patients that also consider the context of the wider health system environment in China.

Prevalence, correlates, and network analysis of Internet addiction symptoms among Chinese pregnant and postpartum women.

OBJECTIVE: Excessive Internet use is a common health problem globally. This study aimed to assess the prevalence, correlates, and network structure of Internet addiction symptoms (Internet addiction hereafter) among Chinese pregnant and postpartum women. METHODS: This was a multicenter cross-sectional study using Internet Addiction Test (IAT) and the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) to evaluate Internet addiction and quality of life (QOL), respectively. Univariate analyses, multivariate logistic regression analyses, and network analyses were performed. RESULTS: Of a total of 1,060 women who completed the study, 320 (30.19%, 95% CI=27.42%-32.96%) women reported Internet addiction during or after pregnancy. Women with previous adverse pregnancy experiences (OR=1.831, P=0.001) and physical comorbidities (OR=1.724, P=0.004) had a higher likelihood of developing Internet addiction. Internet addiction was significantly associated with poor QOL in all domains. Network analyses revealed that IAT item 16 (request an extension for longer time spent online) was the most central symptom in the analyses, and also one of the strongest bridging symptoms linking the Internet addiction and QOL communities. LIMITATIONS: This was a cross-sectional study, all study findings were based on self-reported data, and possible recall bias and selection bias may exist. CONCLUSION: Internet addiction is common among Chinese pregnant and postpartum women, and is significantly associated with lower QOL. Effective strategies, especially focusing on central symptoms, are needed to reduce the impact of Internet addiction and improve QOL in pregnant and postpartum women.

Surface topography index: a novel deformity severity assessment index for pectus excavatum.

BACKGROUND: The surface topography index (STI) has great potential in both routine computed tomography (CT) scan and emerging optical imaging systems. However, the diagnostic accuracy and stability of the STI as a deformity severity assessment index has not been fully confirmed. Therefore, the aim of the present study was to determine the diagnostic performance of the STI as a novel deformity severity assessment index for pectus excavatum. METHODS: The present study consisted of 722 chest CT images from a single center. The standard CT index (CTI) and STI were calculated for all patients. The between-group difference and the level of compliance between the CTI and STI was analyzed by t-test and Pearson correlation. The diagnostic value and optimum discriminatory values of the CTI and STI were calculated by a receiver-operating characteristic (ROC) curve and DeLong's test. RESULTS: The distributions of the CTI and STI were similar and showed a slight overlap between the pectus excavatum (PE) and non-PE groups. Both the CTI and STI significantly differed between the 2 groups (P<0.001). The STI demonstrated a strong Pearson correlation with the CTI (r=0.91, 95% confidence interval: 0.88-0.91, P<0.001). The ROC curves showed that STI =1.58 (sensitivity: 0.93, specificity: 0.95) could be considered equivalent to CTI =2.72 (sensitivity: 0.93, specificity: 0.97) as the optimum discriminatory values. DeLong's test showed no significant difference in the ROC curve results between the CTI and STI (Z=0.90, P=0.37). CONCLUSIONS: The STI has comparative discrimination ability in PE diagnosis and deformity severity assessment when used with the standard CTI. The STI as a novel index is not only an ideal evaluation metric of PE deformity but also an objective trait for PE patients just as weight and height for everyone.

The experiences of Chinese general practitioners in communicating with people with type 2 diabetes-a focus group study.

BACKGROUND: China has more ascertained cases of diabetes than any other country. Much of the care of people with type 2 diabetes (T2DM) in China is managed by GPs and this will increase with the implementation of health care reforms aimed at strengthening China's primary health care system. Diabetes care requires effective communication between physicians and patients, yet little is known about this area in China. We aimed to explore the experiences of Chinese GPs in communicating with diabetes patients and how this may relate to communication skills training. METHODS: Focus groups with Chinese GPs were undertaken. Purposive sampling was used to recruit 15 GPs from Guangzhou city in China. All data were audio-recorded and transcribed. A thematic analysis using the Framework Method was applied to code the data and identify themes. RESULTS: Seven males and 8 females from 12 general practices attended 4 focus groups with a mean age of 37.6 years and 7.5 years' work experience. Four major themes were identified: diversity in diabetic patients, communication with patients, patient-doctor relationship, and communication skills training. GPs reported facing a wide variety of diabetes patients in their daily practice. They believed insufficient knowledge and misunderstanding of diabetes was common among patients. They highlighted several challenges in communicating with diabetes patients, such as insufficient consultation time, poor communication regarding blood glucose monitoring and misunderstanding the risk of complications. They used terms such as "blind spot" or "not on the same channel" to describe gaps in their patients' understanding of diabetes and its management, and cited this as a cause of ineffective patient-doctor communication. Mutual understanding of diabetes was perceived to be an important factor towards building positive patient-doctor relationships. Although GPs believed communication skills training was necessary, they reported rarely received this. CONCLUSIONS: Chinese GPs reported facing challenges in communicating with diabetes patients. Some of these were perceived as being due to the patients themselves, others were attributed to system constraints, and some were seen as related to a lack of clinician training. The study identified key issues for the development of primary care-based management of diabetes in China, and for developing appropriate communication skills training programs for the primary care workforce.

Novel Perbutyrylated Glucose Derivatives of (-)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis, Cytotoxicity, and Molecular Docking.

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7-12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property-activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50 values in the range of 22.90-37.87 µM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.

The Prevalence of Depression and Its Association With Quality of Life Among Pregnant and Postnatal Women in China: A Multicenter Study.

Background: This study examined the prevalence of depressive symptoms (depression hereafter) and its association with quality of life (QOL) among pregnant and postnatal women in China. Methods: In this multi-center, cross-sectional study, 1,060 pregnant and postnatal women from eight hospitals were assessed. Depression and QOL were measured using the Edinburgh Postnatal Depression Scale and the World Health Organization Quality of Life Questionnaire - brief version, respectively. Results: The prevalence of depression was 7.45% (95% CI: 5.87-9.04%) in the sample. Women with depression had lower QOL in physical, psychological, social and environmental domains compared to those without. Women with physical comorbidities were more likely to suffer from depression (OR = 2.391, 95% CI = 1.384-4.130, P = 0.002). Conclusion: Due to its negative association with QOL, increased attention should be paid to depression in pregnant and postnatal women. Regular screening assessment and preventive measures should be adopted to reduce risk of depression in this population.

Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. METHODS: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. RESULTS: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. CONCLUSIONS: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. TRIAL REGISTRATION: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.

Prevalence of Depressive Symptoms Among Pregnant and Postpartum Women in China During the COVID-19 Pandemic.

OBJECTIVE: According to recent studies, the COVID-19 pandemic has been associated with an increased risk of mental health problems across many subpopulations including pregnant and postnatal women. This study examined the prevalence and correlates of depressive symptoms (depression hereafter) in Chinese pregnant and postpartum women during the COVID-19 pandemic. METHODS: This was a multicenter, cross-sectional study comprising 1309 pregnant and postpartum women across 12 provinces in China during the COVID-19 pandemic. Depression was assessed using the nine-item Patient Health Questionnaire. Univariate analyses and multivariate logistic regression analyses were conducted. RESULTS: The prevalence of depression in pregnant and postpartum women was 27.43% (95% confidence interval [CI] = 25.01%-29.85%). Women who were worried about themselves or their babies being infected with COVID-19 (odds ratio [OR] = 2.562, 95% CI = 1.670-3.929), and those who had delayed regular medical checkups (OR = 2.434, 95% CI = 1.580-3.750) were at higher risk of depression. Compared with those living in central and western parts of China, women living in northern (OR = 0.513, 95% CI = 0.326-0.807) and southeastern parts of China (OR = 0.626, 95% CI = 0.463-0.846) were less likely to have depression. CONCLUSIONS: The COVID-19 pandemic was associated with an increased likelihood of mental health problems among pregnant and postnatal women. Over a quarter of the pregnant and postpartum women in China had depression during the COVID-19 pandemic. Considering the negative health impact of depression, preventive measures, regular mental health screening, and medical checkups are needed with the goal to reduce the risk of depression in this vulnerable population during a pandemic.

Combination of eosinophil percentage and high-sensitivity C-reactive protein predicts in-hospital major adverse cardiac events in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Eosinophil levels predict prognosis in ST-segment elevation myocardial infarction (STEMI) patients. Both eosinophils and high-sensitivity C-reactive protein (hs-CRP) play a major role in the acute inflammatory response of myocardial infarction. The purpose of this study was to evaluate eosinophil percentage (EOS%) and hs-CRP as prognostic markers for in-hospital adverse events in STEMI patients undergoing primary percutaneous coronary intervention. METHODS: We retrospectively analyzed the clinical data of 518 patients. Major adverse cardiac events (MACEs) were defined as cardiac rupture, cardiac arrest, malignant arrhythmia, and cardiac death. Based on the receiver operating characteristic (ROC) analysis, all patients were regrouped into 3 groups (None, One, and Two) according to cutoff EOS% value (≤0.3%) and hs-CRP value (>11.8 mg/L). Both Cox regression analyses and the KM (Kaplan-Meier) survival curve were used to examine the prognostic role of combined hs-CRP and EOS% in cardiovascular events. RESULTS: Of the 518 STEMI patients, 50 of them developed MACEs. Patients who developed MACEs had a significantly lower EOS% and higher hs-CRP than patients who remained MACE-free. In the multivariable Cox regression analysis, the highest risk of in-hospital MACEs was constantly observed in patients with a combined low EOS% and elevated hs-CRP. Patients with reduced EOS% and high hs-CRP had significantly higher incidence rates of cardiac rupture (P = .001), cardiac arrest (P = .001), and malignant arrhythmia (P < .001); furthermore, they had the worst cumulative survival compared with the other two groups. CONCLUSION: Combined reduced EOS% and elevated hs-CRP were valuable tools for identifying patients at risk of in-hospital MACEs.

Prognostic value of NT-proBNP in patients with severe COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.

TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-ß1/Smads and activating P53 signaling pathways.

Tissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-ß1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-ß1/Smads and p53 signals.

Correction to: MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice.

The original article [1] contains an error whereby Fig. 7 displays incorrect results; the correct version of Fig. 7 can be viewed ahead in this Correction article and should be considered in place of the original article's version of Fig. 7.

Mussel-Inspired Catechol-Functionalized Hydrogels and Their Medical Applications.

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.

MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice.

BACKGROUND: Receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated necroptosis has been implicated in the progression of myocardial infarction (MI), but the underlying mechanisms, particularly whether microRNAs (miRNAs) are involved, remain largely unknown. RESULTS: A microarray analysis was used to screen for miR-325-3p expression in myocardial tissues from MI mice, and the expression was confirmed with qRT-PCR. The levels of myocardial enzymes were measured using commercial kits, and an echocardiography system was utilized for the detection of cardiac function parameters. The pathological features and infarction sizes of cardiac tissues were examined using H&E, TCC and Masson's trichrome staining, and the amount of cell apoptosis was determined using an in situ TUNEL assay. Cardiomyocytes were isolated and then subjected to hypoxia induction in vitro. The expression of the RIPK1, RIPK3 and phosphorylated MLKL (p-MLKL) proteins was measured using a Western blot. The mouse cardiomyocyte cell viability was analyzed by an MTT assay. The mRNA target of miR-325-3p was predicted using TargetScan v7.2 and then validated using a dual-luciferase reporter assay. The overexpression of miR-325-3p evidently decreased the expression levels of lactate dehydrogenase (LDH), phosphocreatine kinase (CK), superoxide dismutase (SOD) and malondialdehyde (MDA), inhibited left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD), and promoted left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVES). In addition, miR-325-3p overexpression attenuated the degree of injury to the cardiac tissue, decreased the infarct sizes and downregulated the expression of the necrosis-related proteins RIPK1, RIPK3 and p-MLKL. CONCLUSIONS: The RIPK1/RIPK3/p-MLKL axis-induced necroptosis that occurred during MI was mediated by a miRNA module, miR-325-3p, which can effectively ameliorate the symptoms of MI by suppressing the expression of RIPK3.