Xiang Chen’s research while affiliated with Xiangya Hospital of Central South University and other places

Background It has been established that lung cancer is the leading cause of all cancer deaths. This study sought to analyze the epidemiological trends of lung cancer over the past 30 years worldwide. Methods Estimates, including the global, regional, national prevalence, incidence, and years lived with disability (YLDs) of lung cancer from 1990 to 2019, were extracted from the Global Burden of Disease Study 2019 to assess the spatiotemporal dynamics in cases and age-standardized rates (ASR). The estimated annual percentage change (EAPC) was calculated to evaluate the variation in ASR. Besides, estimates of age-sex specific prevalence, decomposition analysis for incident cases, and correlation analysis of the EAPC were conducted in our study. Results Globally, the ASR of lung cancer prevalence, incidence and YLDs in 2019 were 38.84/100,000 persons, 27.66/100,000 persons, and 6.62/100,000 persons, respectively. Over the past 30 years, the ASR of incidence (EAPC = -0.09) decreased, although that of prevalence (EAPC = 0.51) and YLDs (EAPC = 0.03) increased. The global prevalence counts was greater in males than females at all age groups and increased with age, peaking in the 65–69 age group for both sexes. The increase in incidence was mainly attributed to population aging. For YLDs, EAPC was negatively correlated with the human development index ( p = 0.0008) and ASR ( p < 0.0001) in 1990 across nation-level units. Conclusions Lung cancer remains a major public health issue globally, warranting the implementation of scientific and effective measures in different countries and territories to control it.

Gynecological cancers seriously affect the reproductive system of females; diseases include ovarian tumors, uterine tumors, endometrial cancers, cervical cancers, and vulva and vaginal tumors. At present, the diagnosis methods of gynecological cancer are insufficiently sensitive and specific, leading to failure of early disease detection. N⁶-methyladenosine (m⁶A) plays various biological functions in RNA modification and is currently studied extensively. m⁶A modification controls the fate of transcripts and regulates RNA metabolism and biological processes through the interaction of m⁶A methyltransferase (“writer”) and demethylase (“erasers”) and the binding protein decoding m⁶A methylation (“readers”). In the field of epigenetics, m⁶A modification is a dynamic process of reversible regulation of target RNA through its regulatory factors. It plays an important role in many diseases, especially cancer. However, its role in gynecologic cancers has not been fully investigated. Thus, we review the regulatory mechanism, biological functions, and therapeutic prospects of m⁶A RNA methylation regulators in gynecological cancers.

Background The spatiotemporal trend of renal involvement in Coronavirus Disease 2019(COVID-19) patients is still unclear. Therefore, we seek to reveal the dynamics of renal involvement superimposed COVID-19 according to time and space. Methods The COVID-19 patients reporting the renal involvement were enrolled in our study. We collected the following information: the first author, patient demographics, patients enrolled period, location, definition of acute kidney injury (AKI), prevalence of AKI and renal replacement treatment (RRT). Results 17,134 patients were included finally. The overall prevalence of AKI in COVID-19 patients was 19%, which 7% of them underwent RRT. And the overall risk of AKI in patients enrolled before March 1, 2020 (9%) was significantly lower than that after March 1, 2020 (36%) (P < 0.00001). Moreover, the overall risk of AKI outside Asia (35%) was significantly higher than that in Asia (10%) (P < 0.00001). Additionally, similar to patients required RRT, AKI patients would more tend to become seriously ill or even die (P < 0.00001). Conclusions This study firstly reports that renal involvement superimposed COVID-19, a comorbidity portending a poor prognosis, has become an increasingly serious problem over time, and more common outside Asia. Thus, more concerns should be offered to manage the specific group of patients.

Background The global burden of gallbladder and biliary tract cancer (GBTC) is increasing. A comprehensive evaluation of the burden is crucial to improve strategies for GBTC prevention and treatment. Methods The incidence rates, mortality, and disability‐adjusted life years (DALYs) of GBTC from 1990 to 2017 were extracted from the Global Burden of Diseases Study (GBD) 2017. Estimated annual percent changes (EAPCs) were calculated to quantify GBTC trends during the study period. Results Globally, there were 210,878 new cases, 173,974 deaths, and 3,483,046 DALYs because of GBTC in 2017. GBTC incidence increased by 76%, mortality increased by 65%, and DALYs increased by 52% from 1990 to 2017. In addition, relatively higher Socio‐Demographic Index regions had greater incidence and death rates but greatly decreased age‐standardized incidence rate (ASIR) and age‐standardized death rate (ASDR). At the national level, Chile had the highest ASIR (10.38 per 100,000 population) and the highest ASDR (10.43 per 100,000 population) in 2017. The largest increases in ASIR (EAPC, 3.38) and ASDR (EAPC, 3.39) were observed in Georgia. Nonlinear associations were observed between the ASDR, the Socio‐Demographic Index, and DALYs at the 21 GBD regional levels and at the national level. The proportions of GBTC age‐standardized deaths and DALYs attributable to high body mass index were 15.4% and 16%, respectively. Conclusions GBTC remains a major health burden worldwide. These findings are expected to prompt policymakers to establish a cost‐effective method for the early diagnosis, prevention, and treatment of GBTC, reducing its modifiable risk factors and reversing its increasing trends. Lay Summary Although the rates of age‐standardized incidence, death, and disability‐adjusted life‐years for gallbladder and biliary tract cancer decreased from 1990 to 2017, the numbers of these measures increased. Nonlinear associations existed between the age‐standardized death rate, the Socio‐Demographic Index, and disability‐adjusted life‐years at the 21 regional and national levels in the Global Burden of Disease Study.

Background: Hepatocellular carcinoma (HCC) is closely associated with the immune microenvironment. To identify the effective population before administering treatment, the establishment of prognostic immune biomarkers is crucial for early HCC diagnosis and treatment. Results: A total of 335 IRGs identified from 788 overlapping IRGs were associated with the survival of HCC. A prognostic immunoscore model was identified. The Kaplan-Meier survival curves and time-dependent ROC analysis revealed a powerful prognostic performance of immunoscore signature via multi validation. Besides, the immunoscore signature exhibited a better predictive power compared to other prognostic signatures. Gene set enrichment analysis showed multiple signaling differences between the high and low immunoscore group. Furthermore, immunoscore was significantly associated with multiple immune cells and immune infiltration in the tumor microenvironment. Conclusions: We identified the immunoscore as a robust marker for predicting HCC patient survival. Methods: Three sets of immune-related genes (IRGs) were integrated to identify the overlapping IRGs. Weighted gene co-expression network analysis was performed to obtain the survival-related IRGs. Further, the prognostic immunoscore model was constructed via LASSO-penalized Cox regression analysis. Then the prognostic performance of immunoscore was evaluated. In addition, ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between immunoscore and tumor immune microenvironment.

Purpose Gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were involved in the development and progression of cancers. This study aimed to evaluate the prognostic value of a preoperative GGT:ALP ratio (GAR) in hepatocellular carcinoma (HCC) patients with curative liver resection. Patients and Methods A total of 380 HCC patients underwent curative liver resection before December 2017 and from January to December 2018 were included and stratified into training set and validation set, respectively. Prediction accuracy was evaluated by the area under the receiver operating characteristic curve (AUC). Factors determined to be significant for overall survival (OS) and tumor-free survival (TFS) by using Cox regression analysis. The Kaplan–Meier method and Log rank test were utilized for survival analysis. Results The AUC of GAR was 0.70 (P < 0.001). An optimal cut-off value of 0.91 yielded a sensitivity of 78.1% and a specificity of 60.4% for GAR (P < 0.001), which stratified the HCC patients into high-risk (>0.91) and low-risk (≤ 0.91) groups. Time-dependent ROC revealed that the AUCs for 1-, 3-, and 5-year OS predictions for GAR were 0.60, 0.69 and 0.62, respectively. In addition, GAR was identified as an independent risk factor for OS and TFS both in training and validation cohort by univariate and multivariate Cox regression analysis, as well as a good prognostic indicator for patients with Barcelona Clinic Liver Cancer stage C or without vascular invasion. Notably, the AUC of the GAR for survival was better than several potential prognostic indices (P < 0.05). Conclusion We identified the GAR as a prognostic indicator in two independent cohorts of HCC patients with curative liver resection. The patients with decreased GAR score were significantly associated with better OS and TFS.

Background: Nicorandil in reducing contrast-induced nephropathy (CIN) following elective percutaneous coronary intervention (PCI) is an inconsistent practice. This article aims to evaluate the efficacy and safety of nicorandil in preventing CIN after elective PCI. Methods: This is a pooled analysis of patients treated with elective PCI. The primary outcome was the incidence of CIN. The secondary outcomes were major adverse events, including mortality, heart failure, recurrent myocardial infarction, stroke, and renal replacement therapy. Results: A total of 1229 patients were recruited in our study. With statistical significance, nicorandil lowered the risk of CIN (odds ratio = 0.26; 95% confidence interval = 0.16-0.44; P < 0.00001; I2 = 0%) in patients who underwent elective PCI. In addition, no significant differences were observed in the incidence of mortality, heart failure, recurrent myocardial infarction, stroke, and renal replacement therapy between the two groups (P > 0.05). Conclusions: Our article indicated that nicorandil could prevent CIN without increasing the major adverse events. Furthermore, sufficiently powered and randomized clinical studies are still needed in order to determine the role of nicorandil in preventing CIN after elective PCI.

Background and aim: The clinical utility of sorafenib plus hepatic arterial infusion chemotherapy (SoraHAIC) in advanced hepatocellular carcinoma (HCC) patients remains unclear. We, therefore, conducted the current meta-analysis to systematically evaluate the efficacy and safety of SoraHAIC therapy on major outcomes with advanced HCC patients. Methods: A systematic search of The Cochrane Library, PubMed, and Embase databases was performed. The major outcomes in patients with advanced HCC were divided into SoraHAIC group and sorafenib group, which included overall response rate, overall survival, progressive disease, and adverse events. Results: Involving a total of 726 patients from 5 included studies, our meta-analysis demonstrated that SoraHAIC showed significantly more improvement than sorafenib alone in overall response rate [risk ratio=3.08; 95% confidence interval (CI), 1.38-6.89; P=0.006] and complete response (risk ratio=5.84; 95% CI, 1.85-18.45; P=0.003). With regard to survival outcome, the combination therapy also significantly prolongs the median overall survival than sorafenib monotherapy (hazard ratio=0.59; 95% CI, 0.35-1.00; P=0.05). In addition, the risk of adverse events such as anemia, neutropenia, and thrombocytopenia was significantly greater in the combination group than in the sorafenib group (P<0.05 for all). Conclusions: This meta-analysis indicated that SoraHAIC seems to be efficient and safe for advanced HCC patients. However, additional large-scale randomized controlled trials are needed to further investigate the clinical benefit.

Background: The prognosis of hepatocellular carcinoma (HCC) patients remains poor. Identifying prognostic markers to stratify HCC patients might help to improve their outcomes. Methods: Six gene expression profiles (GSE121248, GSE84402, GSE65372, GSE51401, GSE45267 and GSE14520) were obtained for differentially expressed genes (DEGs) analysis between HCC tissues and non-tumor tissues. To identify the prognostic genes and establish risk score model, univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed based on the integrated DEGs by robust rank aggregation method. Then Kaplan-Meier and time-dependent receiver operating characteristic (ROC) curves were generated to validate the prognostic performance of risk score in training datasets and validation datasets. Multivariable Cox regression analysis was used to identify independent prognostic factors in liver cancer. A prognostic nomogram was constructed based on The Cancer Genome Atlas (TCGA) dataset. Finally, the correlation between DNA methylation and prognosis-related genes was analyzed. Results: A twelve-gene signature including SPP1, KIF20A, HMMR, TPX2, LAPTM4B, TTK, MAGEA6, ANX10, LECT2, CYP2C9, RDH16 and LCAT was identified, and risk score was calculated by corresponding coefficients. The risk score model showed a strong diagnosis performance to distinguish HCC from normal samples. The HCC patients were stratified into high-risk and low-risk group based on the cutoff value of risk score. The Kaplan-Meier survival curves revealed significantly favorable overall survival in groups with lower risk score (P < 0.0001). Time-dependent ROC analysis showed well prognostic performance of the twelve-gene signature, which was comparable or superior to AJCC stage at predicting 1-, 3-, and 5-year overall survival. In addition, the twelve-gene signature was independent with other clinical factors and performed better in predicting overall survival after combining with age and AJCC stage by nomogram. Moreover, most of the prognostic twelve genes were negatively correlated with DNA methylation in HCC tissues, which SPP1 and LCAT were identified as the DNA methylation-driven genes. Conclusions: We identified a twelve-gene signature as a robust marker with great potential for clinical application in risk stratification and overall survival prediction in HCC patients.

The clinical outcomes of nicorandil in percutaneous coronary intervention (PCI) are conflicting. We sought to evaluate the effects of nicorandil on periprocedural myocardial injury (PMI) in elective PCI. Eligible studies that reported the effect of nicorandil on PMI in elective PCI were obtained from PubMed, Web of Science, and Cochrane Library (up to October 28, 2019). The outcomes were PMI and major adverse cardiovascular and cerebrovascular events (MACCEs). Ten randomized controlled trials with 1304 patients undergoing elective PCI were evaluated. Nicorandil significantly reduced the incidence of PMI (odds ratio [OR] = 0.48; P = .0003); however, there was no significant difference in MACCEs (OR = 0.80; P = .45) between the 2 groups. Subgroup analyses showed that nicorandil significantly lowered the PMI risk when only patients with stable coronary artery disease (OR = 0.41; P = .0008) were considered and when nicorandil was administered intravenously (OR = 0.41; P = .0007) or orally (OR = 0.33; P = .0001). This meta-analysis suggests that nicorandil could reduce the incidence of PMI without increasing the occurrence of MACCEs in elective PCI. The effect of nicorandil in lowering the PMI risk is associated with the diagnosis of the patients and the route of nicorandil administration.