Metabolomic landscape of overall and common cancers in the UK Biobank: A prospective cohort study.

Information about the NMR metabolomics landscape of overall, and common cancers is still limited. Based on a cohort of 83,290 participants from the UK Biobank, we used multivariate Cox regression to assess the associations between each of the 168 metabolites with the risks of overall cancer and 20 specific types of cancer. Then, we applied LASSO to identify important metabolites for overall cancer risk and obtained their associations using multivariate cox regression. We further conducted mediation analysis to evaluate the mediated role of metabolites in the effects of traditional factors on overall cancer risk. Finally, we included the 13 identified metabolites as predictors in prediction models, and compared the accuracies of our traditional models. We found that there were commonalities among the metabolic profiles of overall and specific types of cancer: the top 20 frequently identified metabolites for 20 specific types of cancer were all associated with overall cancer; most of the specific types of cancer had common identified metabolites. Meanwhile, the associations between the same metabolite with different types of cancer can vary based on the site of origin. We identified 13 metabolic biomarkers associated with overall cancer, and found that they mediated the effects of traditional factors. The accuracies of prediction models improved when we added 13 identified metabolites in models. This study is helpful to understand the metabolic mechanisms of overall and a wide range of cancers, and our results also indicate that NMR metabolites are potential biomarkers in cancer diagnosis and prevention.

Paliperidone Extended Release Versus Olanzapine in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Multicenter Study.

PURPOSE: Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy. METHODS: This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference. RESULTS: Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated. CONCLUSIONS: Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

A composite oral hygiene score and the risk of oral cancer and its subtypes: a large-scale propensity score-based study.

OBJECTIVE: This study aimed to investigate the potential relationship between oral hygiene and the risk of oral cancer and its subtypes after controlling the effects of several confounding factors. MATERIALS AND METHODS: A large-scale case-control study was conducted from January 2010 to August 2019, recruiting a total of 1,288 oral cancer cases with newly diagnosed and 4,234 healthy controls. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to minimize confounding effects. Conditional logistic regression was used to evaluate the effects of oral hygiene indicators on oral cancer. RESULTS: A composite oral hygiene score was developed based on five indicators selected based on PSM and IPTW analysis (including tooth loss, dentures wearing, the frequency of tooth brushing, regular dental visits, and recurrent dental ulcer). Participants with a higher score, compared with their lower counterparts, showed a 49% increased risk (the odds ratio (OR) was 1.49 (95% confidence interval (CI): 1.26-1.75). A similar association pattern was found following IPTW analyses (OR = 1.32; 95% CI: 1.22-1.42). Of note, the adverse effects of poor oral hygiene were more evident among the sites of gingival and buccal (PSM analysis: 2.03-fold and 2.68-fold increased risk; IPTW analysis: 1.57-fold and 2.07-fold increased risk, respectively). Additionally, a greater positive association was observed between poor oral hygiene and oral squamous cell carcinoma, compared with other pathological types. CONCLUSION: This study establishes a composite oral hygiene score and provides supportive evidence of poor oral hygiene associated with a higher risk of oral cancer, particularly in the gingival and buccal mucosa sites and in the squamous cell carcinoma. CLINICAL RELEVANCE: The data highlights the importance of improving poor oral hygiene habits, which has public health implications for the prevention of oral cancer.

[Overview of Meta-analysis of Lianhua Qingwen preparations in treatment of viral diseases].

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.

Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.

BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients. METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University. RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally. CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.

Prenatal evaluation and postnatal outcomes of fetal ovarian cysts.

To evaluate the natural history and outcome of cases of fetal ovarian cyst under conservative prenatal treatment. A retrospective cohort study included patients diagnosed with fetal ovarian cysts was conducted between January 2008 to December 2016. Data including clinical data, sonographic feature and postnatal outcomes were obtained. One hundred and two cases were included for statistical analysis. The rate of spontaneous resolution was significantly higher among cases with simple than complex cysts (70/92 or 76.1% vs 2/10 or 20%, P < .01) and for cysts <4 cm than cysts ≥4 cm (50/56 or 89.3% vs 22/46 or 47.8%, P < .01). Ovarian torsion was confirmed in 5/102 (4.9%) cases; neither prenatal characteristics of cysts (complex: 2/10 or 20% vs simple: 3/92 or 3.3%, P = .07), nor their size (≥40 mm: 4/46 or 8.7% vs < 40 mm: 1/56 or 1.8%, P = .17) was predictive for ovarian torsion. 25/102 (24.5%) of cysts change in size or sonographic characteristics prenatally. Half of the complex cysts at the last prenatal scan are not ovarian in origin. 98/102 neonates (96.1%) were able to preserve both ovaries. Spontaneous resolution of ovarian cysts is predicted by cyst size and characteristics, whereas likelihood of torsion cannot be predicted.

Bayesian estimation of the measurement of interactions in epidemiological studies.

Background: Interaction identification is important in epidemiological studies and can be detected by including a product term in the model. However, as Rothman noted, a product term in exponential models may be regarded as multiplicative rather than additive to better reflect biological interactions. Currently, the additive interaction is largely measured by the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S), and confidence intervals are developed via frequentist approaches. However, few studies have focused on the same issue from a Bayesian perspective. The present study aims to provide a Bayesian view of the estimation and credible intervals of the additive interaction measures. Methods: Bayesian logistic regression was employed, and estimates and credible intervals were calculated from posterior samples of the RERI, AP and S. Since Bayesian inference depends only on posterior samples, it is very easy to apply this method to preventive factors. The validity of the proposed method was verified by comparing the Bayesian method with the delta and bootstrap approaches in simulation studies with example data. Results: In all the simulation studies, the Bayesian estimates were very close to the corresponding true values. Due to the skewness of the interaction measures, compared with the confidence intervals of the delta method, the credible intervals of the Bayesian approach were more balanced and matched the nominal 95% level. Compared with the bootstrap method, the Bayesian method appeared to be a competitive alternative and fared better when small sample sizes were used. Conclusions: The proposed Bayesian method is a competitive alternative to other methods. This approach can assist epidemiologists in detecting additive-scale interactions.

Identification of an additive interaction using parameter regularization and model selection in epidemiology.

Background: In epidemiology, indicators such as the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) are commonly used to assess additive interactions between two variables. However, the results of these indicators are sometimes inconsistent in real world applications and it may be difficult to draw conclusions from them. Method: Based on the relationship between the RERI, AP, and S, we propose a method with consistent results, which are achieved by constraining e θ 3 - e θ 1 - e θ 2 + 1 = 0 , and the interpretation of the results is simple and clear. We present two pathways to achieve this end: one is to complete the constraint by adding a regular penalty term to the model likelihood function; the other is to use model selection. Result: Using simulated and real data, our proposed methods effectively identified additive interactions and proved to be applicable to real-world data. Simulations were used to evaluate the performance of the methods in scenarios with and without additive interactions. The penalty term converged to 0 with increasing λ, and the final models matched the expected interaction status, demonstrating that regularized estimation could effectively identify additive interactions. Model selection was compared with classical methods (delta and bootstrap) across various scenarios with different interaction strengths, and the additive interactions were closely observed and the results aligned closely with bootstrap results. The coefficients in the model without interaction adhered to a simplifying equation, reinforcing that there was no significant interaction between smoking and alcohol use on oral cancer risk. Conclusion: In summary, the model selection method based on the Hannan-Quinn criterion (HQ) appears to be a competitive alternative to the bootstrap method for identifying additive interactions. Furthermore, when using RERI, AP, and S to assess the additive interaction, the results are more consistent and the results are simple and easy to understand.

Rare Cases of Pseudomonas aeruginosa Meningitis in Children: 10-Year Experience in a Single Center.

OBJECTIVE: The primary objective was to elucidate the epidemiologic characteristics, risk determinants, and clinical outcomes associated with Pseudomonas aeruginosa-induced meningitis. METHODS: All cases of meningitis caused by Pseudomonas aeruginosa that were treated at the hospital between 2012 and 2022 were retrospectively analyzed and detailed. RESULTS: During a 10-year period, only 10 patients satisfied the inclusion criteria. Three patients had previously undergone neurosurgical procedures and 4 patients had leukemia. CONCLUSIONS: Although Pseudomonas aeruginosa meningitis possesses a low incidence rate, the rate of mortality is high. Patients with leukemia or those who have undergone neurosurgery are the most susceptible to diagnosis. Cases of severe neutropenia present only mild or no cerebrospinal fluid pleocytosis. In patients with sensitive Pseudomonas aeruginosa meningitis, the timely use of anti-Pseudomonas carbapenems for intravenous treatment is highly effective. For drug-resistant Pseudomonas aeruginosa meningitis, intrathecal polymyxins administration can be an effective treatment option.

Clinical presentations and diagnostic approaches of pediatric necrotizing tracheobronchitis with influenza A virus and Staphylococcus aureus co-infections.

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

Investigating the risk factors for nonadherence to analgesic medications in cancer patients: Establishing a nomogram model.

Objective: The substantial prevalence of nonadherence to analgesic medication among individuals diagnosed with cancer imposes a significant strain on both patients and healthcare resources. The objective of this study is to develop and authenticate a nomogram model for assessing nonadherence to analgesic medication in cancer patients. Methods: Clinical information, demographic data, and medication adherence records of cancer pain patients were gathered from the Affiliated Hospital of Chengde Medical University between April 2020 and March 2023. The risk factors associated with analgesic medication nonadherence in cancer patients were analyzed using the least absolute selection operator (LASSO) regression model and multivariate logistic regression. Additionally, a nomogram model was developed. The bootstrap method was employed to internally verify the model. Discrimination and accuracy of the nomogram model were evaluated using the Concordance index (C-index), area under the receiver Operating characteristic (ROC) curve (AUC), and calibration curve. The potential clinical value of the nomogram model was established through decision curve analysis (DCA) and clinical impact curve. Results: The study included a total of 450 patients, with a nonadherence rate of 43.33%. The model incorporated seven factors: age, address, smoking history, number of comorbidities, use of nonsteroidal antiinflammatory drugs (NSAIDs), use of opioids, and PHQ-8. The C-index of the model was found to be 0.93 (95% CI: 0.907-0.953), and the ROC curve demonstrated an AUC of 0.929. Furthermore, the DCA and clinical impact curves indicate that the built model can accurately predict cancer pain patients' medication adherence performance. Conclusions: A nomogram model based on 7 risk factors has been successfully developed and validated for long-term analgesic management of cancer patients.

Effects of diets on risks of cancer and the mediating role of metabolites.

Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.

Co-Occurring Thrombotic Thrombocytopenic Purpura and Autoimmune Hemolytic Anemia in a Child Carrying the Pathogenic SHOC2 c.4A>G (p.Ser2Gly) Variant.

BACKGROUND RASopathies involve mutations in genes that encode proteins participating in the RAS-mitogen-activated protein kinase pathway and are a collection of multisystem disorders that clinically overlap. Variants in the SHOC2 gene have been reported in Noonan-like syndrome, which include distinct facial features, short stature, congenital cardiac defects, developmental delays, bleeding disorders, and loose anagen hair. This report is of a 7-year-old girl with the c.4A>G (p.Ser2Gly) variant of the SHOC2 gene, consistent with Noonan-like syndrome, with loose anagen hair, presenting with thrombotic thrombocytopenic purpura and autoimmune hemolytic anemia. CASE REPORT The child had a medical history of 7 hospitalizations at our institution. At the age of 2 months, she underwent surgical correction for ventricular and atrial septal defects. At the age of 2 years, tonsil and adenoid removal surgery was performed, followed by surgery for otitis media at age 5 years. At 7 years, she was hospitalized for the simultaneous occurrence of thrombotic thrombocytopenic purpura and autoimmune hemolytic anemia. The patient displayed short stature and mild intellectual disability. Notable facial features included sparse hair, mild frontal bossing, and low-set ears. Antinuclear antibody levels demonstrated a significant gradual shift. Through trio whole-exome sequencing, a c.4A>G (p.Ser2Gly) variation in the SHOC2 gene was identified. CONCLUSIONS Given the clinical information and genetic testing results, the patient's condition appeared to closely be a type of RASopathy. This report has highlighted the importance of physical, developmental, and genetic testing in children presenting with dysmorphism, developmental delay, and hematological abnormalities.

The Landscape of Lipid Metabolism in Lung Cancer: The Role of Structural Profiling.

The aim of this study was to explore the relationship between lipids with different structural features and lung cancer (LC) risk and identify prospective biomarkers of LC. Univariate and multivariate analysis methods were used to screen for differential lipids, and two machine learning methods were used to define combined lipid biomarkers. A lipid score (LS) based on lipid biomarkers was calculated, and a mediation analysis was performed. A total of 605 lipid species spanning 20 individual lipid classes were identified in the plasma lipidome. Higher carbon atoms with dihydroceramide (DCER), phosphatidylethanolamine (PE), and phosphoinositols (PI) presented a significant negative correlation with LC. Point estimates revealed the inverse associated with LC for the n-3 PUFA score. Ten lipids were identified as markers with an area under the curve (AUC) value of 0.947 (95%, CI: 0.879-0.989). In this study, we summarized the potential relationship between lipid molecules with different structural features and LC risk, identified a panel of LC biomarkers, and demonstrated that the n-3 PUFA of the acyl chain of lipids was a protective factor for LC.

Integrating metabolomics and network pharmacology to assess the effects of quercetin on lung inflammatory injury induced by human respiratory syncytial virus.

Quercetin (QR) has significant anti-respiratory syncytial virus (RSV) effects. However, its therapeutic mechanism has not been thoroughly explored. In this study, a lung inflammatory injury model caused by RSV was established in mice. Untargeted lung tissue metabolomics was used to identify differential metabolites and metabolic pathways. Network pharmacology was used to predict potential therapeutic targets of QR and analyze biological functions and pathways modulated by QR. By overlapping the results of the metabolomics and the network pharmacology analyses, the common targets of QR that were likely to be involved in the amelioration of RSV-induced lung inflammatory injury by QR were identified. Metabolomics analysis identified 52 differential metabolites and 244 corresponding targets, while network pharmacology analysis identified 126 potential targets of QR. By intersecting these 244 targets with the 126 targets, hypoxanthine-guanine phosphoribosyltransferase (HPRT1), thymidine phosphorylase (TYMP), lactoperoxidase (LPO), myeloperoxidase (MPO), and cytochrome P450 19A1 (CYP19A1) were identified as the common targets. The key targets, HPRT1, TYMP, LPO, and MPO, were components of purine metabolic pathways. The present study demonstrated that QR effectively ameliorated RSV-induced lung inflammatory injury in the established mouse model. Combining metabolomics and network pharmacology showed that the anti-RSV effect of QR was closely associated with purine metabolism pathways.

Dietary fatty acid patterns and risk of oesophageal squamous cell carcinoma.

Background: To characterize and examine the associations between dietary fatty acid intake patterns and the risk of oesophageal squamous cell carcinoma (ESCC). Methods: A total of 422 patients and 423 controls were recruited. Dietary fatty acids were entered into a factor analysis. Multivariable logistic regression and restricted cubic spline were used to evaluate the risk of ESCC specific for different dietary fatty acid patterns (FAPs). A forest plot was applied to show the association between FAPs and ESCC risk after stratification by lifestyle exposure factors (tobacco smoking, alcohol drinking, pickled food, fried food, hot food, hard food). Results: The factor analysis generated four major fatty acid patterns: a medium- and long-chain SFA (MLC-SFA) pattern; an even-chain unsaturated fatty acid (EC-UFA) pattern, a saturated fatty acid (SFA) pattern and an n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) pattern. In the multivariate-adjusted model, the odds ratios (ORs) with 95% confidence intervals (CIs) of ESCC were 2.07 (1.31, 3.26) and 0.53 (0.34, 0.81) for the highest versus the lowest tertiles of the EC-UFA pattern and n-3 LC-PUFA pattern, respectively. The MLC-SFA and SFA patterns were not associated with ESCC. An association between FAPs and ESCC risk after stratification by lifestyle exposure factors was also observed. Conclusions: Our study indicates that the EC-UFA pattern and n-3 LC-PUFA pattern intake are associated with ESCC, providing a potential dietary intervention for ESCC prevention.

Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism.

Background: Necroptosis and inflammation are closely related to the pathogenesis of respiratory syncytial virus (RSV). Acteoside (AC), a natural phenylpropanoid glycoside from Kuding Tea, has significant anti-RSV effect. However, the roles of AC on RSV-induced lung necroptosis and inflammation are yet to be elucidated. Methods: The effects of AC were investigated in BALB/c mice and A549 cells. Lung histopathology was observed through H&E staining. The viral titer was assessed via plaque assay. The RSV-F expression was determined by RT-qPCR and immunohistochemistry assay. The levels of cytokines were detected by ELISA and RT-qPCR. The necroptosis rate and mitochondrial membrane potential were evaluated via flow cytometry. The expressions of HMGB1/NF-κB and RIP1/RIP3/MLKL/PGAM5/DRP1 were detected by western blot. Additionally, untargeted metabolomics was conducted to investigate the metabolic profiles and related metabolic pathways via Gas Chromatography-Mass Spectrometry. Results: The results showed that compared with the RSV-infected group, AC treatment significantly attenuated lung pathological damage, virus replication, and cytokines levels. AC also alleviated RSV-induced necroptosis and mitochondrial dysfunction in vitro and in vivo. Moreover, AC treatment down-regulated the expression of HMGB1, p-Iκbα/Iκbα, p-p65/p65, RIP1, RIP3, MLKL, PGAM5, and DRP1. Furthermore, metabolomic analyses suggested that the perturbations in major metabolites of AC therapy were related to variations in amino acid and energy metabolism. Conclusion: Our findings validated the beneficial effects of AC in suppressing necroptosis and regulating metabolism, suggesting AC may be a new drug candidate for RSV infection.

Spatial Analysis and Comparison of the Economic Burden of Common Diseases: An Investigation of 5.7 Million Rural Elderly Inpatients in Southeast China, 2010-2016.

Background: As China embraced an aging society, the burden of age-related diseases had increased dramatically. Knowledge about spatial distribution characteristics of disease burden and the influencing factors of medical expenditure is of great significance to the formulation of health policies. However, related research in rural China is still insufficient. Methods: A total of 5,744,717 records of hospitalized rural elderly in southeast China were collected from 2010 to 2016. We described the temporal trends of hospitalization medical expenditure and the prevalence of catastrophic health expenses (CHE) in the rural elderly by common diseases. Then, geographical information tools were used for visualization of geographic distribution patterns of CHE, the ordinary least squares methods (OLS) and geographically weighted regression (GWR) were employed to examine the influencing factors of medical expenditure. Results: The number of CHE hospitalizations and the total number of hospitalizations for the rural elderly people increased by 2.1 times and 2.2 times, respectively, from 2010 to 2016. Counties with a high prevalence of CHE were clustered in the eastern coastal area (Moran's I = 0.620, P < 0.001, General G < 0.001, P < 0.001). Unspecified transport accidents, cardiovascular disease, and essential hypertension were the top causes of CHE in the rural elderly. Adequate hospital beds (P < 0.05) and reasonable utilization and distribution of town-level (P < 0.001) and county-level hospitals (P < 0.001) may help reduce medical expenditures. Conclusions: In the context of an aging society, the disease burden for the elderly in rural areas should arouse more attention. These findings highlight the importance of age-related disease prevention and the rational allocation of medical resources in rural areas.

Oxymatrine inhibits proliferation and apoptosis of human breast cancer cells through the regulation of miRNA-140-5P.

OBJECTIVE: Oxymatrine has shown strong anti-cancer ability, but its mechanism is not well-studied. METHODS: The inhibitory rates of oxymatrine with various concentrations (0, 1, 2, 4, 6, 8, 16, 32 mg/ml) on MCF-7 cells were detected by CCK-8. The effects of oxymatrine on the expression of miRNA-140-5P in MCF-7 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). miRNA-140-5P mimics or NC mimics were transfected into cells using Lipofectamine 2000. Eventually, the cells were divided into control-group, drug-group, miRNA-140-5P mimics group, NC mimics group, and miRNA-140-5P mimics + drug group. Cell viability was detected by CCK-8 assay and apoptosis rate of each group were measured by using Flow cytometry. Western blot was carried out to detect the protein expression of TGFBR1 and FGF9. RESULTS: Oxymatrine at various concentrations had conspicuous inhibitory effect on the proliferation of MCF-7 cells (P<0.05), and the inhibitory effect of oxymatrine on MCF-7 cells showed both dose- and time-dependent manners. The relative expression of miRNA-140-5P in MCF cells was remarkably lower than that in MCF-10A. Oxymatrine could effectively promote the expression of miRNA-140-5P in MCF-7 cells, and the relative expression of miRNA-140-5P increased significantly with the increased dose of oxymatrine (P<0.05). Both transfection of miRNA-140-5P mimics and oxymatrine treatment could reduce the proliferation of MCF-7 cells (P<0.05), and the proliferation of cells in miRNA-140-5P mimics + drug-group was significantly lower than that of other groups (P<0.05). Compared with the control-group, the protein expressions of TGFbR1 and FGF9 in low-dose, medium-dose and high-dose groups were dramatically decreased (P<0.05), in a dose-dependent manner (P<0.05). CONCLUSION: Oxymatrine inhibits proliferation and promotes cell apoptosis of breast cancer MCF-7 cells. The mechanism may contribute to the regulation of miRNA-140-5p and its target genes.