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Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC).LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells.The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway.Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.

China is one of the countries with the heaviest burden of hepatitis C virus (HCV) worldwide, especially subtype 1b. To better control hepatitis C, insights into the characteristics of dynamic spread and genomic mutations are urgently needed. We retrieved sequences of HCV-1b NS5B among intravenous drug users (IDUs) and general people (Non-IDUs) in China from 2000 to 2011 in NCBI. Bayesian phylogenetic and phylogeographic analyses were used to evaluate the transmission dynamics of HCV-1b. Non-synonymous substitutions were detected to illustrate immune adaptation. Evolutionary history demonstrated that HCV-1b effective population size experienced a sharp increase in 1990. HCV-1b sequences among IDUs had a higher estimated evolutionary rate (5.7185 × 10

Background Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia. Methods This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1–9 days of the illness course) and the late BAL layer (received BAL within 10–14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups. Results Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p p Conclusion For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications.

Siling Xu,1 Lu Liu,1 Guoqing Yin,1 Abdul-Quddus Mohammed,1 Xian Lv,1 Cailing Feng,1 Tingting Shi,1 Fuad A Abdu,1 Wenliang Che1,2 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiology, Shanghai Tenth People’s Hospital Chongming Branch, Shanghai, People’s Republic of ChinaCorrespondence: Wenliang Che; Fuad A AbduDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Jingan District, Shanghai, 200072, People’s Republic of ChinaTel +86-21-66307259Fax +86-21-66301051Email chewenliang@tongji.edu.cn; 1691026@tongji.edu.cnPurpose: The association of serum uric acid (SUA) levels with cardiovascular outcomes in patients with coronary artery disease (CAD) has been extensively studied and yielded conflicting results. We aimed to investigate whether the severity of coronary stenosis and ischemia influences the prognostic impact of SUA levels in patients with CAD undergoing D-SPECT.Patients and Methods: This study consecutively included patients who were admitted for CAD in Shanghai Tenth People’s Hospital between June 2014 and August 2018, had complete SUA data and underwent both coronary angiography and D-SPECT within 3 months. Hyperuricemia was defined as an SUA level of > 7 mg/dL in men and > 6 mg/dL in women. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, unplanned coronary revascularization, nonfatal myocardial infarction, ischemic stroke, heart failure, and angina-related hospitalization.Results: A total of 695 patients were included, of whom 432 (62.2%) presented with obstructive CAD and 117 (16.8%) had hyperuricemia. During a median follow-up of 26 months, the incidence rates of MACE in patients with hyperuricemia and normouricemia were 15.2% and 21.1%, respectively. After a multivariable adjustment, hyperuricemia was significantly associated with an increased risk of MACE (HR: 1.39, 95% CI: 1.03– 1.87, p = 0.033) when compared with normouricemia. When repeating the primary analysis in patients with and without obstructive CAD, we showed that hyperuricemia was independently associated with an 80% increased risk of MACE among patients with nonobstructive CAD (HR: 1.80, 95% CI: 1.04– 3.11, p = 0.035), while such a significant association was not found among those with obstructive CAD (HR: 1.18, 95% CI: 0.82– 1.72, p = 0.373). Moreover, we uncovered a U-shaped and linear trajectory of SUA levels with MACE in the obstructive and nonobstructive CAD, respectively. The sex-specific analysis showed that the adverse impact of hyperuricemia was only pronounced in males (HR: 1.73, 95% CI: 1.18– 2.53, p = 0.005) but not in females (HR: 0.98, 95% CI: 0.57– 1.66, p = 0.933).Conclusion: Hyperuricemia is significantly associated with increased risk of MACE in the nonobstructive CAD rather than in the obstructive CAD.Keywords: coronary artery disease, serum uric acid, D-SPECT, nonobstructive, outcomes

Background Some children hospitalized for severe pertussis need intensive care; moreover, some children die because of deterioration alone or in combination with other complications. The purpose of this study was to identify the mortality risk factors among hospitalized children with severe pertussis. Methods This study evaluated the medical records of 144 hospitalized children with severe pertussis at the Guangzhou Women and Children’s Medical Centre between January 2016 and December 2019. Results The median age of patients was 2 months (IQR 1–4 months), with 90.3% of the patients aged 70.0 × 109/L (odds ratio [OR], 230.66; 95% confidence interval [CI], 5.16–10,319.09 P = 0.005) and pulmonary hypertension (PH) (OR 323.29; 95% CI 16.01–6529.42; P Conclusion Severe pertussis mainly occurred in children aged 70.0 × 109/L and PH were the prognostic independent variables associated with death.

Background Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). Methods CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. Results Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR Conclusion CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.

ObjectiveCoronary microvascular dysfunction (CMD) may associate with adverse cardiovascular events in obese patients. Coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed as a less-invasive and pressure-wire-free index to assess CMD. We aimed to investigate the impact of coronary microvascular function assessed by caIMR in patients with overweight and chronic coronary syndrome (CCS).MethodsCCS patients who underwent coronary angiography between 2015 to 2018 were included. Overweight was defined as BMI≥24.0kg/m². Impaired coronary microvascular function was defined as caIMR≥25U. The patients were classified according to BMI and caIMR. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier and Cox regression analyses evaluated the association between caIMR and MACE.ResultsTwo hundred and eighty-two CCS patients were enrolled. Among these, 169 (59.93%) were overweight. Impaired coronary microvascular function was higher in overweight patients than in patients with normal weight (49.70% vs. 38.05%; P=0.035). During 35 months of follow-up, 33 MACE had occurred. Among the total CCS population, MACE was higher in patients with high caIMR than in low caIMR (18.11% vs. 6.45%, P=0.003). In subgroups analysis, MACE was higher in overweight patients with high caIMR than low caIMR (20.24% vs. 7.06%, P=0.014), while there were no significant differences in normal-weight patients. Multivariate Cox analysis demonstrated that caIMR≥25 was independently associated with MACE in overweight patients (HR, 2.87; 95% CI, 1.12-7.30; P=0.027) but not in the normal-weight patients. In addition, caIMR showed a significant predictive value for adverse outcomes in overweight patients and provided an incremental prediction when added to a prediction model with BMI.ConclusionsImpaired coronary microvascular function assessed by caIMR was common and is an independent predictor of MACE in overweight patients with CCS.

Background: Some children hospitalized due to severe community-acquired pneumonia (CAP) require to the pediatric intensive care unit (PICU) because of severe complications. The purpose of this study was to identify the risk factors for mortality in this patient population. Methods: This study evaluated the medical records of 113 hospitalized children with severe CAP, who were transferred to the PICU within 48 h of admission at the Guangzhou Women and Children's Medical Center between 2013 and 2017. Results: The study group consisted of 87 boys (77%) and 26 girls (33%), aged between 1 month and 9 years; 72.6% (82/113) of patients were aged 3 on admission, not receiving corticosteroid therapy prior to admission, the need for mechanical ventilation, septic shock, multi-organ dysfunction (MODS), and acute renal failure (ARF) occurring prior to transfer to the PICU, increased alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, and decreased hemoglobin and albumin (ALB) levels were associated with mortality (P

Cholangiocarcinoma is the most common biliary duct malignancy and the second most common primary liver cancer, accounting for 10‑20% of hepatic malignancies. With high mortality and poor prognosis, the 5‑year survival rate of cholangiocarcinoma is only 10%. A previous study demonstrated a significant association between aspirin use and a decreased risk of cholangiocarcinoma. However, the effect of aspirin on cholangiocarcinoma remains unknown. Therefore, the aim of the present study was to investigate the effects of aspirin on cholangiocarcinoma in vitro and in vivo. Three cholangiocarcinoma cell lines were used to analyze the effect of aspirin on cell proliferation, cell cycle progression, apoptosis, and the regulation of microRNAs. MicroRNAs are known to regulate the development and progression of various types of cancer. An HuCCT‑1 xenograft model was used for the in vivo study. It was determined that aspirin inhibited the proliferation of human cholangiocarcinoma cells (except TKKK cells). Aspirin induced cell cycle arrest in the G0/G1 phase and regulated cell‑cycle related proteins in cholangiocarcinoma cells (HuCCT‑1 cells) but did not induce apoptosis. The expression of miR‑340‑5p was significantly upregulated after treatment, and overexpression of miR‑340‑5p inhibited the proliferation of HuCCT‑1 cells and decreased the levels of cyclin D1. TKKK cells had low miR‑340‑5p expression, which may explain why aspirin had no effect on their proliferation. In vivo, aspirin reduced the growth of xenografted tumors. In conclusion, the present study indicated that aspirin partially inhibited cholangiocarcinoma cell proliferation and tumor growth by inducing G0/G1 phase cell cycle arrest, potentially through the miR‑340‑5p/cyclin D1 axis.

Context Findings from observational studies indicate an association of thyroid hormone levels with the risk of nonalcoholic fatty liver disease (NAFLD); however, conflicting results remain and reverse causality may be a possibility. Objective This study aimed to evaluate the associations between NAFLD and both plasma thyroxine (T4) and thyroid stimulating hormone (TSH) at the phenotypic and genetic levels. Methods We included 14 797 participants, aged 20 to 74 years who had undergone abdominal ultrasonography during the Third National Health and Nutrition Examination Survey (NHANES III). Multivariable logistic regression analyses were used to examine the observational associations of TSH and T4 with NAFLD. Mediation analyses were performed to study whether the relationship between NAFLD and TSH levels was mediated via potential confounders. A bidirectional, two-sample Mendelian randomization (MR) analysis was used to determine the potential causal relationship. Results Multivariable logistic regression model suggested a “dose-response” relationship between TSH (Q4 vs Q1: OR = 1.29; 95% CI, 1.10-1.52; Ptrend = 0.001) and NAFLD. BMI and ALT partially mediated the association between TSH and NAFLD, while the proportion of the mediation effects of BMI and ALT were 39.1% and 22.3%, respectively. In MR analyses, the inverse-variance weighted method was selected as primary method and suggested a putative causal effect of NAFLD on serum TSH levels (OR = 1.022; 95% CI, 1.002-1.043). The result was further validated in the sensitivity analyses. Conclusion Circulating TSH levels were associated with the risk of NAFLD. MR analysis suggested a putative causal effect of NAFLD on TSH levels.

Summary Purpose The association between famine exposure and type 2 diabetes (T2DM) remains controversial. A meta-analysis was performed to clarify the relation of famine exposure to T2DM risk in detail. Methods A systematic literature search was performed in PubMed, Cochrane library, Web of Science, China National Knowledge Infrastructure (CNKI), Sinomed (CBM), Wanfang Data Knowledge Service Platform and China Science and Technology Journal VIP Database. The articles were limited to be available in English or Chinese before 10 April 2019. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of famine exposure on T2DM. The I square value (I2) was used to assess heterogeneity, and the random effects model (REM) was adopted as the pooling method. Results This meta-analysis included 24 published articles with 1,660,385 subjects. A significant association of famine exposure with increased risk of T2DM was observed (RR = 1.433, 95% CI: 1.101–1.865). The pooled RRs were different in terms of publication year, location, study design, sample size, famine duration and definition of diabetes (criteria). Longer the famine exposure experienced, greater the effect of famine exposure on T2DM would be. Compared to WHO criteria, studies of which diabetes diagnosed by ADA criteria and other criteria might more likely to find this association. Compared to moderate famine exposure, the pooled RR in severe famine was statistically significant. Furthermore, the pooled RR adjusted for the most confounders in females was 1.517 (95% CI: 1.018–2.261). In terms of period of famine exposure, compared to adult exposure, people who exposure famine in fetal, childhood, and adolescent were likely to be diabetes. Conclusion Famine exposure may increase the risk of T2DM. The risk may vary with famine duration, definition of diabetes, gender and period of famine exposure.

BRAF is among the most frequently mutated oncogenes in human cancers. Multiple small molecule BRAF kinase inhibitors have been approved for treating melanoma carrying BRAF-V600 mutations. However, the benefits of BRAF kinase inhibitors are generally short-lived. Small molecule-mediated targeted protein degradation has recently emerged as a novel pharmaceutical strategy to remove disease proteins through hijacking the cellular ubiquitin proteasome system (UPS). In this study, we developed thalidomide-based heterobifunctional compounds that induced selective degradation of BRAF-V600E, but not the wild-type BRAF. Downregulation of BRAF-V600E suppressed the MEK/ERK kinase cascade in melanoma cells and impaired cell growth in culture. Abolishing the interaction between degraders and cereblon or blocking the UPS significantly impaired the activities of these degraders, validating a mechanistic role of UPS in mediating targeted degradation of BRAF-V600E. These findings highlight a new approach to modulate the functions of oncogenic BRAF mutants and provide a framework to treat BRAF-dependent human cancers.

Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis in the infarcted heart, remain poorly understood. Using an AMI mouse model, we identified gasdermin D (GSDMD) in activated leukocytes early in AMI. We demonstrated that GSDMD is required for enhanced early mobilization of neutrophils to the infarcted heart. Loss of GSDMD resulted in attenuated IL-1β release from neutrophils and subsequent decreased neutrophils and monocytes in the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function, and increased survival post AMI. Through a series of bone marrow transplantation studies and leukocytes depletion experiments, we further clarified that excessive bone marrow derived and GSDMD-dependent early neutrophil production and mobilization (24 hours post AMI), contributed to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection post AMI, through reduction of scar size and enhancement of heart function. Our study provides new mechanistic insights into molecular regulation of neutrophil generation and mobilization after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.

Assessment of population vulnerability and adaptive capacity under climate change is crucial for informing conservation strategies. Sang et al. assemble a reference genome for Populus koreana and combine population genomics and modelling to predict spatiotemporal responses to climate change.Rapid global climate change is posing a substantial threat to biodiversity. The assessment of population vulnerability and adaptive capacity under climate change is crucial for informing conservation and mitigation strategies. Here we generate a chromosome-scale genome assembly and re-sequence genomes of 230 individuals collected from 24 populations for Populus koreana, a pioneer and keystone tree species in temperate forests of East Asia. We integrate population genomics and environmental variables to reveal a set of climate-associated single-nucleotide polymorphisms, insertion/deletions and structural variations, especially numerous adaptive non-coding variants distributed across the genome. We incorporate these variants into an environmental modeling scheme to predict a highly spatiotemporal shift of this species in response to future climate change. We further identify the most vulnerable populations that need conservation priority and many candidate genes and variants that may be useful for forest tree breeding with special aims. Our findings highlight the importance of integrating genomic and environmental data to predict adaptive capacity of a key forest to rapid climate change in the future.

Severe pneumonia related to human adenoviruses (HAdVs) has a high lethality rate in children and its early diagnosis and treatment remain a major challenge. Circular RNAs (circRNAs) are novel long noncoding RNAs that play important roles in gene regulation and disease pathogenesis. To investigate the roles of circRNAs in HAdV pneumonia, we analyzed the circRNA profiles of healthy children and children with HAdV pneumonia, including both mild and severe cases, and identified 139 significantly upregulated circRNAs in children with HAdV pneumonia vs healthy controls and 18 significantly upregulated circRNAs in children with severe HAdV pneumonia vs mild HAdV pneumonia. In particular, hsa_circ_0002171 was differentially expressed in both groups and might thus be useful as a diagnostic biomarker of HAdV pneumonia and severe HAdV pneumonia. To identify the underlying mechanisms of circRNAs in HAdV pneumonia, we analyzed the transcriptome of children with HAdV pneumonia and established a circRNA-mRNA regulatory network. Enrichment analysis of differentially expressed target mRNAs demonstrated that the differentially expressed genes between healthy controls and HAdV pneumonia patients were mainly involved in RNA splicing while the differentially expressed genes between children with mild and severe HAdV pneumonia were mainly involved in regulating lymphocyte activation. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0002171 had a significant value in the diagnosis of HAdV pneumonia and of severe HAdV pneumonia. Taken together, the circRNA expression profile was altered in children with HAdV pneumonia. These results demonstrated that hsa_circ_0002171 is a potential diagnostic biomarker of HAdV pneumonia.

Communicated by Ramaswamy H. Sarma.

Objective To evaluate the association between periodontitis and the incidence and mortality of gastrointestinal cancer. Method A comprehensive literature search was conducted to identify all relevant studies published prior to April 2019 according to the established inclusion criteria. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Results We identified 10 studies with 26 estimates of the relationship between periodontitis and gastrointestinal cancer. The HR for the incidence of gastrointestinal cancer in periodontitis was 1.23 (95% CI: 1.10-1.37). Subgroup analyses showed that periodontitis was associated with an increased risk of gastrointestinal cancers in prospective cohort studies and high-quality studies, North American individuals, and individuals 18 years or older, as well as when the dental status was self-reported and when the study was adjusted for smoking. A meta-analysis of nine reports demonstrated that periodontitis was associated with increased mortality from gastrointestinal cancer (HR = 1.59, 95% CI: 1.16-2.16). Additionally, periodontitis was associated with mortality from pancreatic cancer (HR = 2.20, 95% CI: 1.44-3.37); thus, periodontitis may be a risk factor for pancreatic cancer. Conclusion Our meta-analysis demonstrated that periodontitis may be a risk factor for gastrointestinal cancers. Additional prospective cohort studies are warranted to confirm these findings.

Background Very few studies have focused on the relationship between ambient apparent temperature (AT) and admission of mental and behaviour disorders (MDs). Therefore, a time-series study was conducted in Yancheng, China, to explore the effects of AT on the daily emergency admissions of patients with MDs over the period of 2014–17. Methods A quasi-Poisson generalized linear model (GLM) combined with a distributed lag non-linear model (DLNM) was adopted to explore the associations after adjusting for time trend, day of the week, humidity, sunshine duration, rainfall, holidays and air pollutants. In the subgroup analysis, the modification effects of age and sex were also examined. Results Overall, 8438 cases of MDs emergency admissions were identified. With the apparent temperature with the minimum number of admissions (− 3.4 °C) serving as a reference, a positive correlation emerged between high AT and daily emergency admissions of patients with MDs in Yancheng, China, with the lagged effect of 1 to 5 days. The subgroup analysis demonstrated a positive relationship between AT and MDs emergency admissions among males and individuals younger than 45 years old, with no lagged effect. Conclusions The results will provide important scientific evidence for mental health policy-makers and practitioners for possible intervention, especially among the vulnerable populations.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Sorafenib has been used as a first-line systemic treatment for over a decade. However, resistance to sorafenib limits patient response and presents a major hurdle during HCC treatment. Lenvatinib has been approved as a first-line systemic treatment for advanced HCC and is the first agent to achieve non-inferiority against sorafenib. Therefore, in the present study, we evaluated the inhibition efficacy of lenvatinib in sorafenib-resistant HCC cells. Only a few studies have been conducted on this topic. Two human HCC cell lines, Huh-7 and Hep-3B, were used to establish sorafenib resistance, and in vitro and in vivo studies were employed. Lenvatinib suppressed sorafenib-resistant HCC cell proliferation mainly by inducing G1 cell cycle arrest through ERK signaling. Hep-3B sorafenib-resistant cells showed partial cross-resistance to lenvatinib, possibly due to the contribution of poor autophagic responsiveness. Overall, the findings suggest that the underlying mechanism of lenvatinib in overcoming sorafenib resistance in HCC involves FGFR4-ERK signaling. Lenvatinib may be a suitable second-line therapy for unresectable HCC patients who have developed sorafenib resistance and express FGFR4.

Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae) is a major cause of community‑acquired pneumonia in children. In some cases, M. pneumoniae pneumonia (MPP) can develop into refractory MPP (RMPP), which shows no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. However, the pathogenesis of RMPP remains poorly understood. The present study aimed to identify target genes that could be used as biomarkers for the clinical diagnosis of early‑stage RMPP through high‑throughput sequencing technology. The differences in long non‑coding (lnc)RNAs, mRNAs and circular (circ)RNAs were examined between whole‑blood samples from two patients with non‑refractory MPP (NRMPP), two patients with RMPP and three healthy children using ribosomal (r)RNA‑depleted RNA‑sequencing techniques and an integrated mRNA/circRNA analysis. A total of 17 lncRNAs (four upregulated and 13 downregulated), 18 mRNAs (six upregulated and 12 downregulated) and 24 circRNAs (12 upregulated and 12 downregulated) were the most significantly differentially expressed (P

Recently, insects have aroused the interest of researchers as potential therapeutic resources against malignant diseases such as cancer. In this study, the effects of aqueous extracts from mysore thorn borer (MTB) (Anoplophora chinensis) and mealworm larvae (MWL) (Tenebrio molitor) against cancer cells were investigated. MWL aqueous extract showed higher antiproliferative effects against Caco-2 and HepG2 cells compared to MTB. The IC50 (48 hr) of MWL aqueous extract were 11.44 and 20 mg/ml for Caco-2 and HepG2 respectively. Flow cytometry analysis showed that MWL aqueous extract induced apoptosis in Caco-2 and HepG2 increasing from 2.06% to 74.34% and from 0.04% to 42.14% after 24 hr respectively. Caspase activity assay showed that apoptosis was mediated via death receptor pathway mediated by caspase-8 and -9 followed by the activation of caspase-3; caspase-3 may have induced DNA damage and cell death. These effects may be correlated to its free amino acids. The results of this study demonstrate the potentials of MWL in the development of natural anticancer therapeutics in the future. PRACTICAL APPLICATIONS: Natural nutraceuticals from insects might be useful for the treatment and prevention of cancers such as colorectal and liver cancer. In recent years, edible insects have caught the attention of researchers, because of their potential as an alternative source of food and nutraceuticals. The results of our study showed that MWL extract might provide important anticancer compounds against colon and liver cancer.

ObjectiveTo describe the prevalence and variations of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) among children and adolescents (CADs) and young adults (YADs).DesignA population-based observational study.SettingAnnual cases and prevalence of NAFLD/NASH from 1990 to 2017, by sex, region and country were collected from the Global Burden of Disease database.Main outcome measuresThe estimated annual percentage change, which was calculated by a regression line, was used to quantify the temporal trends in NAFLD/NASH burden among young people at the global, regional and national levels.ResultsGlobally, NAFLD/NASH incidence increased from 19.34 million in 1990 to 29.49 million in 2017 among CADs, with an annual increase of 1.35%. Additionally, in YADs, the number of cases and NAFLD/NASH prevalence significantly increased during this period, independent of sex and region. The greatest NAFLD/NASH increase was in North Africa and the Middle East. Almost all countries showed an increasing trend from 1990 to 2017, with the most pronounced increase observed in the developed regions.ConclusionsThe epidemiology of NAFLD/NASH in young people has changed considerably over the last three decades. Both the prevalence and number of cases have increased irrespective of sex, age and region. This phenomenon can result in a predictable increase in chronic liver disease burden in the near future. Understanding the prevalence of NAFLD/NASH and its variations is of paramount importance to develop strategies to implement public health policy.

Due to the potencies in the treatments of cancer, infectious diseases, and autoimmune diseases, the developments of human TLR8 (hTLR8) agonists and antagonists have attracted widespread attentions. The hTLR8 agonists and antagonists have similar structures but with completely opposite biological effects. Up to date, the subtle differences in the structures between the hTLR8 agonists and antagonists are still unknown. In this work, emerging chemical pattern (ECP) was successfully used to extract the key chemical patterns of the hTLR8 agonists and antagonists. By using CAEP classifier, an optimal ECP model with only 3 descriptors was established with the overall prediction accuracy larger than 90%. Further hierarchical cluster analysis and molecular docking showed that the H-bond and hydrophobic properties are the key features distinguishing the hTLR8 agonists from antagonists. Comparing with the antagonists, the agonists show stronger specific H-bond properties, while antagonists have stronger non-specific hydrophobic properties. The significant differences in the structural properties may be closely related to the activation/inhibition mechanism of hTLR8.

The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted in hopes of producing progress on this topic. A systematic database search was performed in electronic databases, including the Chinese Biomedical Database (CBM), PubMed, Web of Science, and the Cochrane Library. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by a random-effects model. Statistical heterogeneity was assessed with Cochran's Q test and the I2 statistic. From 1462 potentially eligible records, 15 studies met the inclusion criteria. Subjects with OH had a high risk of heart failure (HF) and atrial fibrillation (AF) (pooled HR 1.34, 95% CI 1.17-1.52, P < 0.001 and pooled HR 1.51, 95% CI 1.28-1.79, P < 0.001, respectively). This meta-analysis also showed significant associations between OH and the risks of developing coronary heart disease (CHD) (pooled HR 1.44, 95% CI 1.18-1.75, P < 0.001) and myocardial infarction (MI) (pooled HR 1.52, 95% CI 1.12-2.06, P = 0.008). Our study suggests that OH is positively associated with high risks of HF and AF. Moreover, it may be related to high risks of CHD and MI.

BACKGROUND Osteosarcoma is one of the most common bone tumors, with strong local aggressiveness and early metastasis. The aim of this study was to describe the epidemiological data and evaluate the prognostic factors for overall survival (OS) and cause-specific survival (CSS) in patients with non-metastatic osteosarcoma. MATERIAL AND METHODS Patients histologically diagnosed with non-metastatic osteosarcoma between 2005 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning, and Lasso regression were used to identify the prognostic factors for OS and CSS, and the accuracy of the nomograms was tested and compared with the American Joint Committee on Cancer (AJCC) staging systems. RESULTS The entire cohort comprised 1000 patients with non-metastatic osteosarcoma. The multivariable analysis suggested that age, tumor size, grade, and American Joint Committee on Cancer (AJCC) T staging were independent prognostic factors for OS and CSS. Additionally, the nomograms based on these results could better predict probability of OS (Internal validation C-index, 0.7095) and CSS (0.7100) compared with the sixth (OS: 0.613; CSS: 0.628) and seventh edition AJCC staging systems (0.602, 0.613). CONCLUSIONS Relatively young age and low histopathological grade were favorable factors for both OS and CSS. Nomograms based on multivariable models worked well in predicting the probability of death for patients with non-metastatic osteosarcoma.

Previous epidemiological investigations have evaluated the association between gout, serum uric acid levels, and obstructive sleep apnea syndrome (OSAS), but with inconsistent results. We conducted this meta-analysis aiming at providing clear evidence about whether OSAS patients have higher serum uric acid levels and more susceptible to gout. Relevant studies were identified via electronic databases from inception to December 17, 2018. Study selection was conducted according to predesigned eligibility criteria, and two authors independently extracted data from included studies. The hazard ratio (HR) and weighted mean difference (WMD) and their corresponding 95% confidence interval (CI) were derived using random-effects models. We conducted meta-, heterogeneity, publication bias, sensitivity, and subgroup analyses. Eighteen studies, involving a total of 157,607 individuals (32,395 with OSAS, 125,212 without OSAS) and 12,262 gout cases, were included. Results show that serum uric acid levels are elevated in patients with OSAS (WMD = 52.25, 95% CI 36.16-64.33); OSAS did not reach statistical significance as a predictor of gout (but there was a trend, HR = 1.25, 95% CI 0.91-1.70) and that the association between OSAS and serum uric acid was quite robust. OSAS may be a potential risk factor for hyperuricemia and the development of gout and thus, effective OSAS therapy may present as a valuable preventive measure against gout. Still, it is vital to undertake clinical studies with better designing to corroborate these associations and shed new light on it.

The aim of this study was to explore the relationship between statin use and the risk of pancreatic cancer.Electronic databases were searched to identify relevant studies published until January 2018. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with random-effects model. Subgroup analyses and sensitivity analysis were also conducted. Cochran Q test and I(2) statistic were used to evaluate the heterogeneity.Twenty-six studies were included that contained more than 3 million participants and 170,000 pancreatic cancer patients. The overall result demonstrated a significant decrease in pancreatic cancer risk with statin use (RR, 0.84; 95% CI, 0.73-0.97; P = 0.000; I(2) = 84.4%). In subgroup analyses, nonsignificant association was detected between long-term statin use and the risk of pancreatic cancer (RR, 0.98; 95% CI, 0.86-1.11; P = 0.718; I(2) = 0.0%). Meanwhile, there was nonsignificant association between the use of lipophilic statins and the risk of pancreatic cancer (RR, 0.98; 95% CI, 0.84-1.15; P = 0.853; I(2) = 27.2%). No publication bias was found in this meta-analysis.The overall result of this meta-analysis supports the hypothesis that statins have a protective effect on pancreatic cancer. Furthermore, high-quality randomized clinical trials and cohort studies are needed to confirm these findings.

Background Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that infects immunodeficient children. The aim of the study is to determine the clinical features and peripheral immune state of Talaromyces marneffei (T. marneffei) infections in children for early detection and diagnosis. Methods We retrospectively reviewed 21 pediatric patients who were diagnosed with T. marneffei infections and were followed up in the Guangzhou Women and Children’s Medical Center from January 2010 to January 2020. For each patient, we collected and analyzed clinical characteristics, peripheral immunological results, genetic tests, complications and prognosis. Results Common clinical features of the patients included fever (20/21, 95.24%), cough (17/21, 80.95%) and hepatomegaly (17/21, 80.95%). Severe complications included septic shock (12/21, 57.14%), hemophagocytic lymphohistiocytosis (HLH) (11/21, 52.38%), acute respiratory distress syndrome (ARDS) (10/21, 47.62%), multiple organ dysfunction syndrome (MODS) (9/21, 42.86%), and disseminated intravascular coagulation (DIC) (7/21, 33.33%). Eleven children (11/21, 52.38%) eventually died of T. marneffei infections. All patients were HIV negative. Seven cases revealed reduced antibody levels, especially IgG. Higher levels of IgE were detected in 9 cases with an obvious increase in two patients. Ten patients showed decreased complement C3 levels, some of whom had low C4 levels. Three patients displayed decreased absolute T lymphocyte counts, including the CD 4+ and CD 8+ subsets. A reduction in NK cells was present in most patients. No patient had positive nitro blue tetrazolium (NBT) test results. Nine patients were screened for common genetic mutations. Of the cases, one case had no disease-specific gene mutation. Four children had confirmed hyperimmunoglobulin M syndrome (HIGM) with CD40LG variation, one case had severe combined immunodeficiency (SCID), and one case had hyper-IgE syndrome (HIES). One patient was identified as having a heterozygous mutation in STAT3 gene; however, he showed no typical clinical manifestations of HIES at his age. One patient had a mutated COPA gene with uncertain pathogenic potential. Another patient was diagnosed with HIES that depended on her clinical features and the National Institutes of Health (NIH) scoring system. Conclusions T. marneffei infections in HIV-negative children induced severe systemic complications and poor prognosis. Children with T. marneffei infections commonly exhibited abnormal immunoglobulin levels in peripheral blood, particularly decreased IgG or increased IgE levels, further suggesting possible underlying PIDs in these patients.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) has been and remained a puzzling heterogeneous entity. The index of microcirculatory resistance (IMR) is a quantitative and specific index for the assessment of microvascular function. However, the role of IMR in MINOCA has not yet been studied. This study aimed to evaluate the prognostic value of coronary microvascular function, as assessed by coronary angiography‑derived index of microvascular resistance (caIMR) in MINOCA patients. Method This study included 109 MINOCA patients. Microvascular function was assessed by caIMR and was analyzed in 280 coronary arteries. The primary endpoint of the study was MACE, defined as cardiovascular death, nonfatal MI, heart failure, stroke and angina rehospitalization. The best cut-off of caIMR was derived from ROC analysis based on MACE prediction. Results The patients were classified into high caIMR (caIMR>43U) and low caIMR (caIMR≤43U) based on a caIMR cut-off value of 43U. High caIMR was observed in 55 (50.5%) patients. A total of 27 MACE occurred during the 2 years of follow-up. MACE rate was significantly higher in patients with high caIMR than in patients with low caIMR (36.4% vs 13.0%, P=0.005). The Kaplan–Meier curves showed a significantly increased risk of MACE in patients with high caIMR (log-rank P=0.001). Cox multivariate analysis showed that caIMR>43 was a highly independent predictor of MACE (HR, 3.08; 95% CI, 1.13 - 8.35; P=0.027). Conclusions caIMR is a strong predictor of clinical outcome among MINOCA patients. The evaluation of IMR can provide an objective risk stratification method for patients with MINOCA.

Chlamydia trachomatis is the most common bacterial pathogen causing sexually transmitted diseases. C. trachomatis infection is closely related to the development of cervical cancer, studies have shown that C. trachomatis can induce host cell autophagy. The autophagy related gene p62 plays an important role in the process of autophagy. To further understand the role of autophagy-associated gene p62 in autophagy of HeLa cells induced by C. trachomatis, p62-silencing cell line, HeLa229-shp62, and control cell line, HeLa229-shNC, were constructed, and a C. trachomatis-infected cell model was established. The autophagosome and C. trachomatis inclusions were observed under electron microscope. The autophagy level of C. trachomatis-infected HeLa cells was detected by Western blot. The results suggested that knockdown of p62 affected neither C. trachomatis infection of HeLa cells nor the initiation of C. trachomatis-induced autophagy, but at 48 h post C. trachomatis infection, autophagy levels were significantly inhibited in p62 silencing host cells. The study demonstrated the important role of p62 in the autophagy induced by C. trachomatis in HeLa cells, which could provide data support and theoretical basis for exploring the pathogenesis and prevention of C. trachomatis.

The Over-The-Scope Clip (OTSC) can effectively treat refractory gastrointestinal diseases. However, most reports have focused on short-term effectiveness. We examined clinical outcomes of the deployed clips and long-term characteristics.Of 47 patients with OTSC treatment, 35 with follow-up periods of ≥3 months were retrospectively examined. The indications were 11 bleedings, 17 perforations, and seven fistulas. The observation period was defined as medium-term (3 to12 months) or long-term (≥12 months). The primary outcome was the clinical success rate without disease recurrence. The secondary outcomes were the complication rate, survival duration, and clip retention rate.The medium- and long-term clinical success rates were 100% during the observation period (median, 44 months; range, 3-78 months). The complication rate was 2.9% (Regardless of clip detachment, the OTSC can be effective in long-term.

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, has been spreading globally. We aimed to develop a clinical model to predict the outcome of patients with severe COVID-19 infection early. Methods Demographic, clinical and first laboratory findings after admission of 183 patients with severe COVID-19 infection (115 survivors and 68 non-survivors from the Sino-French New City Branch of Tongji Hospital, Wuhan) were used to develop the predictive models. Machine learning approaches were used to select the features and predict the patients’ outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models’ performance. A total of 64 with severe COVID-19 infection from the Optical Valley Branch of Tongji Hospital, Wuhan, were used to externally validate the final predictive model. Results The baseline characteristics and laboratory tests were significantly different between the survivors and non-survivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the external validation sets were 0.881. The sensitivity and specificity were 0.839 and 0.794 for the validation set, when using a probability of death of 50% as the cutoff. Risk score based on the selected variables can be used to assess the mortality risk. The predictive model is available at [https://phenomics.fudan.edu.cn/risk_scores/]. Conclusions Age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level of COVID-19 patients at admission are informative for the patients’ outcomes.

To explore the capability of algorithms to build multivariate models integrating morphological and texture features derived from preoperative TA total of 80 patients at our hospital who underwent abdominal MR imaging and were diagnosed with GC from December 2011 to November 2016 were retrospectively included. Texture features were calculated using TThere were 8, 10, and 3 texture parameters that showed significant differences in GCs at different overall (I-II vs. III-IV), T (1-2 vs. 3-4), and N (- vs. +) stages (all p0.05), respectively. Mild thickening was more common in stages I-II, T1-2, and N- GCs (all p0.05). An irregular outer contour was more commonly observed in stages III-IV (p = 0.001) and T3-4 (p = 0.001) GCs. T3-4 and N+ GCs tended to be thickening type lesions (p = 0.005 and 0.032, respectively). The multivariate models using the naive bayes algorithm showed the highest diagnostic efficacy in predicting T and N stages (area under the ROC curves [AUC] = 0.900 and 0.863, respectively), and the model based on regression analysis had the best predictive performance in overall staging (AUC = 0.839).Multivariate models combining morphological characteristics with texture parameters based on machine learning algorithms were able to improve diagnostic efficacy in predicting the overall, T, and N stages of GCs.

The road traffic accident is an important public health issue affecting social development and public safety. The purpose of this study is to describe the situation of traffic accidents, and to explore the relationship between fatal traffic accidents and risk factors in Suzhou city of Anhui province in China. The accident data was obtained from the Traffic Police Detachment of the Suzhou Public Security Bureau. Other vehicle, population and road information are derived from Suzhou Statistical Yearbook. Descriptive analysis was used to summarize road traffic accident participants' characteristics. The binary logistic regression model was used to analyze the factors that affected fatal traffic accident. There are 7,795 cases involved 18,774 road traffic participants. By logistic regression, we found that in Suzhou, overloading makes traffic accidents more likely to be the most fatal traffic accidents (adjusted OR = 5.33, 95%CI: 2.60-10.93). Speeding, drive after drinking, fatigue driving and pedestrian reasons might also increase the probability of fatal traffic accidents. These findings would help transportation authorities identify dangerous driving behaviors and take the necessary measures to improve road safety in undeveloped areas.

Background Endoscopic submucosal tunnel dissection (ESTD) has recently been an effective procedure for resecting large early esophageal neoplasm. However, excessive dissection beyond the distal limit may occur because the prepared distal end often cannot be distinguished through the tunnel. This study aimed to assess the efficacy and safety of a novel crystal violet navigation (CVN) for identifying the distal end. Material and methods In the observational case series study, all 22 patients who underwent esophageal ESTD using the CVN were included. When setting the distal end, the distal incision line was dyed purple using a crystal violet solution. The rates of purple color identified via the tunnel, successful tunnel penetration without extra dissection, en bloc and curative resection, procedure time for ESTD and CVN, and procedure-associated complications were evaluated. Results The rates of purple color and successful tunnel penetration were both 100%. En bloc and curative resection were 100%, and 86%, respectively. The mean total procedure time was 103.9 ± 46.2 (mean ± SD) minutes, while the mean time for the CVN was 14.1 ± 3.44 s. No complications were observed. Conclusions The simple CVN method can be a navigation tool for identifying the distal end during the ESTD procedure.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is one of the leading causes of cancer-related deaths worldwide. Regorafenib, a multi-kinase inhibitor, is used as a second-line treatment for advanced HCC. Here, we aimed to investigate the mechanism of the antitumor effect of regorafenib on HCC and evaluate altered microRNA (miRNA) expression. Cell proliferation was examined in six HCC cell lines (HuH-7, HepG2, HLF, PLC/PRF/5, Hep3B, and Li-7) using the Cell Counting Kit-8 assay. Xenografted mouse models were used to assess the effects of regorafenib in vivo. Cell cycle analysis, western blotting analysis, and miRNA expression analysis were performed to identify the antitumor inhibitory potential of regorafenib on HCC cells. Regorafenib suppressed proliferation in HuH-7 cell and induced G0/G1 cell cycle arrest and cyclin D1 downregulation in regorafenib-sensitive cells. During miRNA analysis, miRNA molecules associated with the antitumor effect of regorafenib were found. Regorafenib suppresses cell proliferation and tumor growth in HCC by decreasing cyclin D1 via alterations in intracellular and exosomal miRNAs in HCC.

Objective: This study was designed to evaluate the expression of microRNA-223 (miRNA-223) in patient-derived eutopic and ectopic endometrial stromal cells (SCs). Given the fact that miRNA-223 was previously shown to be upregulated in these cells and that this upregulation has been linked to epithelial-to-mesenchymal transition (EMT) during endometriosis, this study aimed to further explore the expression of miRNA-223, its effect in endometriosis, and the mechanisms underlying its effects. Methods: Endometrial tissue was collected from 26 patients with endometriosis and 14 patients with hysteromyoma (control group). Primary endometrial SCs were isolated and cultured from several endometrial samples and miRNA-223 expression was evaluated using qRT-PCR. Cells were then transfected with a miRNA-223 overexpression lentiviral vector (sh-miR-223 cells) or an empty control (sh-NC cells) and then used to monitor the effects of miRNA-223 on the expression of several EMT-associated proteins, including N-cadherin, vimentin, and Slug, using western blot. Cellular migration, invasion, and proliferation were then evaluated using a wound healing, Transwell, and CCK-8 assay, respectively. Flow cytometry was used to detect apoptosis. Results: There was a significant decrease in the expression of miRNA-223 in both eutopic and ectopic endometrial SCs (p < 0.05) whereas upregulation of miRNA-223 inhibited the expression of EMT-related molecules and reduced cell migration, invasion, and proliferation. High levels of miRNA-223 also promoted apoptosis. Conclusion: miRNA-223 expression decreased in endometrial SCs from endometriosis patients, which may facilitate the differential regulation of EMT during endometriosis. Clinical Trial registration number: SWYX2020-211.

Objective While some individual studies have suggested an association between periodontal disease and breast cancer, there has not been a formal meta-analysis that collates the existing evidence supporting the hypothesis that periodontal disease leads to a higher risk of developing breast cancer. Accordingly, this meta-analysis was conducted. Methods Relevant studies published until April 2018 were retrieved and were screened according to established inclusion criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to assess the association between periodontal disease and the risk of breast cancer and fixed effect models were used according to the results of the heterogeneity test. Results Eight studies, involving 168,111 individuals, were identified as having explored the association between periodontal disease and breast cancer. Summary estimates in view of adjusted data showed that periodontal disease did increase susceptibility to breast cancer (RR = 1.18, 95%CI: 1.11-1.26, I2 = 17.6%), with robust results confirmed by sensitivity analysis. Conclusion Our results provided evidence of a modest positive association between periodontal disease and breast cancer. Implementation of practical measures to prevent and treat periodontal disease is of great public health significance. Moreover, additional studies are recommended to explore this topic in more detail.

Purposes: Many studies have indicated that orthostatic hypotension (OH) may be a risk factor for dementia and stroke, but the results have been inconsistent. To further ascertain the links between ...

Oridonin has significant liver-protective effects, but its effect on liver steatosis has not been reported. We investigated the effects of oridonin on liver steatosis by cell cultures. The optimal experimental concentration of oridonin was determined through cytotoxicity experiments. A simple steatosis liver cell model was induced using free fatty acids (FFA). After adding oridonin to the FFA-induced cell model for 24 h, the lipid droplets and triglyceride (TG) content in the cells were measured by Oil Red O staining and TG kits. The expressions of autophagy-related markers (cyclin dependent kinases inhibitor 1a (p21), Beclin-1, microtubule-associated protein light chain 3 (LC3)-I and LC3-II, protein kinase B (AKT), phosphorylated-AKT (p-AKT), AMP-activated protein kinase (AMPK), and phosphorylated-AMPK (p-AMPK)) were detected by Western blot. Based on the results, the cell model was further treated by autophagy inhibitor 3-methyladenine (3-MA) to determine the degree of steatosis and the expressions of autophagy-related factors. Oridonin at a concentration higher than 10 μmol/L caused cytotoxicity to the cells. Adding 10 μmol/L oridonin to the FFA-induced cell model effectively reduced lipid droplets and TG content in the cells. Oridonin up-regulated p21, Beclin-1 and LC3-II expressions, but down-regulated those of p62 and LC3-I. Also, oridonin increased the ratios of LC3-II/LC3-I and p-AMPK/AMPK, but reduced that of p-AKT/AKT. With the addition of 3-MA, the effect of oridonin on reducing steatosis was partially reversed, and the autophagy was inhibited. This study found that oridonin can activate autophagy, thereby preventing simple steatosis of liver cells.

Hepatocellular carcinoma (HCC) is a common liver malignancy with high morbidity and poor prognosis. Long non-coding RNAs (lncRNAs) are involved in crucial biological processes of tumorigenesis and progression, and play four major regulatory roles, namely signal, decoy, guide, and scaffold, to regulate gene expression. Through these processes, lncRNAs can target microRNAs (miRNAs) to form lncRNA and miRNA networks, which regulate cancer cell proliferation, metastasis, drug resistance, and the tumor microenvironment. Here, we summarize the multifaceted functions of lncRNA and miRNA networks in the pathogenesis of HCC, the potential use of diagnostic or prognostic biomarkers, and novel therapeutic targets in HCC. This review also highlights the regulatory effects of lncRNA and miRNA networks in the tumor microenvironment of HCC.

Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer regulation, including modulation of cell cycle progression, apoptosis, metastasis, angiogenesis, autophagy, therapy resistance, and epithelial–mesenchymal transition. Several miRNAs have been found to be dysregulated in CCA and are associated with CCA-related risk factors. Accumulating studies have indicated that the expression of altered miRNAs could act as oncogenic or suppressor miRNAs in the development and progression of CCA and contribute to clinical diagnosis and prognosis prediction as potential biomarkers. Furthermore, miRNAs and their target genes also contribute to targeted therapy development and aid in the determination of drug resistance mechanisms. This review aims to summarize the roles of miRNAs in the pathogenesis of CCA, their potential use as biomarkers of diagnosis and prognosis, and their utilization as novel therapeutic targets in CCA.

Premembrane (prM) is a viral protein of flavivirus, which is important for the generation of infectious virion and for virus infection to the host. However, the biological properties and function of the prM of Avian Tembusu virus (ATMUV) have scarcely been studied to date. Monoclonal antibodies (mAbs) are a powerful tool for functional analysis of viral protein. To produce a mAb against prM protein of ATMUV, the prM gene sequence was amplified by reverse transcription polymerase chain reaction (RT-PCR) and cloned into the prokaryotic expression vector pET-28a (+). The recombinant prM protein was successfully expressed in BL21 (DE3). Using the purified prM as immunogen in mice, three hybridoma cells secreting mAbs against prM protein were obtained. These mAbs showed a strong reaction with ATMUV-infected DF-1 cells and pEGFP-C3-prM transfected 293-T cells in both Western blotting analysis and immunofluorescence assay. The mAbs developed in this study will be useful tools for analysis of the prM protein functions on ATMUV infection and the interaction between prM and its host molecules.

ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial‐mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes. Microarray analysis indicated that ZEB1 may function as a downstream factor of ABCB5. Furthermore, the expression of ZEB1 in tissues is positively relevant to ABCB5 in breast cancer. Knocking down ZEB1 inhibits ABCB5 ectopic expression-induced migration and invasion, as well as EMT. Taken together, these results helped to realize the oncogene functions of ABCB5 in breast cancer cells and provided a new direction in treating breast cancer.

Aspirin, a nonsteroidal anti-inflammatory drug (NSAID), is known to inhibit cell proliferation in a variety of cancers. However, the underlying mechanism of this inhibition remains unknown. We investigated the effects of aspirin on hepatocellular carcinoma (HCC) cells using in vitro and in vivo models. Six HCC cell lines and a liver cancer cell line including Huh-7 were used in assays that evaluated cell proliferation, cell cycle, and apoptosis. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), western blot analysis, and phosphorylated receptor tyrosine kinase array were used to evaluate the effects of aspirin on the cells, and microRNAs (miRNAs) were analyzed by a miRNA array chip. The results were validated in vivo using a nude mouse model of Huh-7-xenografted tumors. Our results showed that aspirin exhibited an antiproliferative effect on all cell lines. Moreover, aspirin induced G0/G1 cell cycle arrest and modulated the levels of cell cycle-related molecules such as cyclin E, cyclin D1, and cyclin-dependent kinase 2 (Cdk2). In addition, aspirin upregulated the levels of caspase-cleaved cytokeratin 18, increased the proportion of early apoptotic cells, decreased the levels of clusterin and heat shock protein 70 (HSP 70), upregulated the levels of miRNA-137 and inhibited epidermal growth factor receptor (EGFR) activation. In addition, we observed that aspirin suppressed cell proliferation partially through the miRNA-137/EGFR pathway. Our in vivo results showed that aspirin reduced the growth of xenograft tumors in nude mice. In conclusion, aspirin was able to inhibit the growth of HCC cells by cell cycle arrest, apoptosis, and alteration of miRNA levels in in vitro and in vivo models.

The relation between autophagy and Chlamydia trachomatis infection remain inconclusive. In order to further understand the role of autophagy in C. trachomatis-infected cells. Atg5 silenced HeLa229 cell line was used to establish an autophagy inhibition C. trachomatis infection model. The results suggested that Atg5 served a key regulatory role in the autophagy of C. trachomatis-infected cells. Silencing Atg5 significantly inhibited the autophagy level of the infected cells. Furthermore, Atg5 knockdown led to increased secretion of proinflammatory cytokines IL-1β, IL-6, IFN-γ and TNF-α, and decreased secretion of anti-inflammatory cytokine IL-10 in C. trachomatis-infected cells after autophagy induction, which suggested the anti-inflammatory role of autophagy during chlamydia infection. This study reveals some physiological and pathological roles of autophagy during C. trachomatis infection, which would provide clues in the treatment of chronic chlamydia infection.

Recently, emerging studies on the relationship between insomnia, the most common sleep disorder, and cancer have been published, but with inconsistent results. With the development of society and the accelerated pace of life, more and more people experience insomnia. Therefore, it is important to clarify the association. Relevant literature was obtained through a search of seven databases and supplementary searches. After a strict screening, eight cohort studies (seven prospective and one retrospective) involving 578,809 participants and 7,451 cancer events were incorporated into our analysis. The results demonstrate a modest 24% overall increased risk of cancer for individuals with insomnia in comparison to those without insomnia. The sensitivity analysis shows that the correlation between the two is stable. Subgroup analyses show that the risk of developing cancer was significantly higher in studies conducted in women (HR = 1.24; 95% CI, 1.01-1.53), but not in men (HR = 1.28; 95% CI, 0.90-1.80). Similarly, in terms of specific cancer types, the pooled HR was only significantly higher in thyroid cancer (HR = 1.36; 95% CI, 1.12-1.65) and not in other types of cancer (p > 0.05). Our findings suggest that insomnia may serve as an early warning sign of the onset of cancer and provide an opportunity for early detection and early intervention. Our findings should be treated with caution because of the limited number of included studies and potential bias. More additional studies are warranted to provide more information on the carcinogenic effect of insomnia.

The pathogenesis of Mycoplasma pneumoniae pneumonia (MPP), specifically the local immune responses in the lungs, is poorly understood. In this study, flow cytometry was used to analyze IL-17 and related cytokines in plasma and bronchoalveolar lavage fluid (BALF) samples from 18 and 30 pediatric patients with general MPP (GMPP) and refractory MPP (RMPP), respectively. The levels of IL-1Ra, IL-6, IL-8, IL-17, and TNF-α were significantly elevated in the BALF of MPP children compared to the plasma (P0.01). Although the plasma IL-6 levels in the children with RMPP were higher than those in the children with GMPP (P0.05), the IL-17 levels showed the opposite trend (P0.05). The children with RMPP had significantly higher BALF levels of IL-8, IL-17, and TNF-α than the children with GMPP (P0.05), and the elevated levels of IL-17 correlated with the increased focal size of the lung lesions (P0.05). The elevated levels of IL-17 and related cytokines in the BALF samples could indicate that the local inflammatory response should be distinguished from the systemic inflammatory response in children with MPP. Moreover, RMPP might involve an aggravated inflammatory progression at the site of infection. The levels of IL-17 might correlate with the extent and severity of the lung lesions in MPP.