Curcumol effectively improves obesity through GDF15 induction via activation of endoplasmic reticulum stress response.

The escalating prevalence of obesity presents a formidable global health challenge, underscoring the imperative for efficacious pharmacotherapeutic interventions. However, current anti-obesity medications often exhibit limited efficacy and adverse effects, necessitating the exploration of alternative therapeutic approaches. Growth differentiation factor 15 (GDF15) has emerged as a promising target for obesity management, given its crucial role in appetite control and metabolic regulation. In this study, we aimed to investigate the efficacy of curcumol, a sesquiterpene compound derived from plants of the Zingiberaceae family, in obesity treatment. Our findings demonstrate that curcumol effectively induces the expression of GDF15 through the activation of the endoplasmic reticulum stress pathway. To confirm the role of GDF15 as a critical target for curcumol's function, we compared the effects of curcumol in wild-type mice and Gdf15-knockout mice. Using a high-fat diet-induced obese murine model, we observed that curcumol led to reduced appetite and altered dietary preferences mediated by GDF15. Furthermore, chronic curcumol intervention resulted in promising anti-obesity effects. Additionally, curcumol administration improved glucose tolerance and lipid metabolism in the obese mice. These findings highlight the potential of curcumol as a GDF15 inducer and suggest innovative strategies for managing obesity and its associated metabolic disorders. In conclusion, our study provides evidence for the efficacy of curcumol in obesity treatment by inducing GDF15 expression. The identified effects of curcumol on appetite regulation, dietary preferences, glucose tolerance, and lipid metabolism emphasize its potential as a therapeutic agent for combating obesity and related metabolic disorders.

Dissecting the antitumor effects of Scutellaria barbata: Initial insights into the metabolism of scutellarin and luteolin by gut microbiota.

The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components-scutellarin and luteolin-which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.

The changes of intestinal microbiota and metabolomics during the inhibition of bladder cancer by liquiritigenin.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.

BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood. PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions. METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation. RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation. CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.

Biotransformation of antioxidant eriocitrin into characteristic metabolites by the gut microbiota.

Eriocitrin is a flavonoid glycoside with strong antioxidant capacity that has a variety of pharmacological activities, such as hypolipidemic, anticancer and anti-inflammatory effects. We found that the gut microbiota could rapidly metabolize eriocitrin. By using LC/MSn-IT-TOF, we identified three metabolites of eriocitrin metabolized in the intestinal microbiota: eriodictyol-7-O-glucoside, eriodictyol, and dihydrocaffeic acid. By comparing these two metabolic pathways of eriocitrin (the gut microbiota and liver microsomes), the intestinal microbiota may be the primary metabolic site of eriocitrin metabolism. These findings provide a theoretical foundation for the study of pharmacologically active substances.

Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase.

Specnuezhenide (SNZ) is among the main components of Fructus Ligustri Lucidi, which has anti-inflammation, anti-oxidation, and anti-tumor effect. The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ. In this study, the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored. SNZ can be rapidly metabolized by the gut microbiome, and two intestinal bacterial metabolites of SNZ, salidroside and tyrosol, were discovered. In addition, carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism. At the same time, no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate, indicating that the gut microbiota is the main part involved in the metabolism of SNZ. In addition, pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota. Interestingly, tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ, which indicated that SNZ exhibited potential to inhibit tumor growth, and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues. At the same time, SNZ modulated the structure of gut microbiota and fungal group, which may be the mechanism governing the antitumoral activity of SNZ. Furthermore, SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo. In the future, targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

The LMR-SSIGN-MAPS model predicts disease-free survival in patients with localized clear cell renal cell carcinoma.

Introduction: Prediction models are increasingly being used to predict outcomes after surgery, and such a model would be a precious tool for patients with clear cell renal cell carcinoma (ccRCC) after surgery. Aim: To develop a comprehensive model for predicting disease-free survival (DFS) in patients with localized ccRCC. Material and methods: In a retrospective analysis of 612 patients, least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to identify significant predictors, and then risk factors were used to construct a prognostic model. Harrell's concordance index (C-index) was used to assess the accuracy of the model. Results: The lymphocyte-to-monocyte ratio (LMR), Mayo Clinic stage, size, grade, necrosis score (SSIGN), and Mayo adhesive probability score (MAPS) were the significant risk factors screened by LASSO Cox regression and reconfirmed by multivariate Cox regression analysis in 44 variables. Then a model was constructed by combining the LMR, SSIGN, and MAPS. The C-index of the LMR-SSIGN-MAPS model was greater than the SSIGN score alone. Kaplan-Meier survival analysis demonstrated a significant association between higher LMR-SSIGN-MAPS score and poorer DFS. Conclusions: The LMR-SSIGN-MAPS model, which consists of preoperative inflammation biomarkers, a perinephric adipose tissue image-based scoring system, and pathological features, showed the strengths of easy-to-use and high predictability and might also be used as a promising prognosis model in predicting DFS for patients with localized ccRCC.

Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue.

Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.

Impact of the uniaxial strain on terahertz modulation characteristics in flexible epitaxial VO2 film across the phase transition.

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO2) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

Understanding key determinants of health climate in building construction projects.

Health climate is critical for achieving a better health performance in building construction projects. However, the topic is rarely investigated by extant literature. The aim of this study is to identify key determinants of health climate in building construction projects. To achieve this goal, a hypothesis was established between practitioners' perceptions of health climate and their health status, based on a comprehensive literature review and structured interviews conducted with experienced experts. Then, a questionnaire was developed and administered for data collection. Partial least-squares structural equation modeling was used for data processing and hypothesis test. Results showed that health climate in building construction projects is positively correlated with the health status of the practitioners, and that employment involvement was the most important determinant of health climate in building construction projects, followed by management commitment, and supportive environment. Moreover, significant factors under each determinant of health climate were also disclosed. As limited research has been conducted to examine health climate in building construction projects, this study bridges the knowledge gap and is a contributory work to the current body of knowledge of construction health. Additionally, the findings of this study can provide authorities and practitioners with a deeper understanding of construction health and thereby helping them bring forward more feasible measures to improve health in building construction projects. Thus, this study is useful to the practice as well.

Urine PD-L1 is a tumor tissue candidate substitute and is associated with poor survival in muscle-invasive bladder cancer patients.

Programmed death molecule ligand 1 (PD-L1) expression in urothelial carcinoma is a predictive marker used to guide immunotherapy. As expression of PD-L1 may be heterogeneous in the tumor tissue space, it cannot be accurately determined by immunohistochemical analysis. In this study, we examined PD-L1 protein levels in preoperative urine samples from bladder cancer patients, evaluated the prevalence of PD-L1 in urine, examined the usefulness of urine as a surrogate for PD-L1 expression in tumors, and compared PD-L1 expression in postoperative pathological sections. We found that PD-L1 in urine and tumor tissue correlated well and that it may be able to some extent serve as a surrogate for tissues in bladder cancer and thus predict risk of recurrence in muscle-invasive bladder cancer (MIBC) patients. Our findings reveal the clinical relevance of urine PD-L1 as a noninvasive prognostic indicator for immunotherapy and offer clinical translational suggestions for eventual development of a prognostic model for immunotherapy for bladder cancer.

Lactate: The Mediator of Metabolism and Immunosuppression.

The Warburg effect, one of the hallmarks of tumors, produces large amounts of lactate and generates an acidic tumor microenvironment via using glucose for glycolysis. As a metabolite, lactate not only serves as a substrate to provide energy for supporting cell growth and development but also acts as an important signal molecule to affect the biochemical functions of intracellular proteins and regulate the biological functions of different kinds of cells. Notably, histone lysine lactylation (Kla) is identified as a novel post-modification and carcinogenic signal, which provides the promising and potential therapeutic targets for tumors. Therefore, the metabolism and functional mechanism of lactate are becoming one of the hot fields in tumor research. Here, we review the production of lactate and its regulation on immunosuppressive cells, as well as the important role of Kla in hepatocellular carcinoma. Lactate and Kla supplement the knowledge gap in oncology and pave the way for exploring the mechanism of oncogenesis and therapeutic targets. Research is still needed in this field.

Resumption of anticoagulation therapy after spontaneous intracerebral hemorrhage with patients mechanical heart valves.

Background: Patients with mechanical heart valves are usually maintained on anticoagulation therapy. However, after a spontaneous intracerebral hemorrhage event, administration of anticoagulants is temporarily ceased, and it remains unclear when to restart anticoagulation therapy. Methods: A cohort study was conducted to investigate the optimal time for restarting anticoagulation in patients with mechanical heart valves after spontaneous intracerebral hemorrhage. All patients with mechanical valves who experienced spontaneous cerebral hemorrhage and were admitted to the Second Affiliated Hospital of the Zhejiang University Medical School between 2013 and 2018 were retrospectively enrolled in this study. The patient electronic medical records were reviewed and the correlation between the time of restarting anticoagulation (within 3 days or more than 3 days after hemorrhage) and patient prognosis was assessed. Results: A total of 40 patients with mechanical heart valves who experienced spontaneous cerebral hemorrhage were enrolled in this study. All patients were given oral warfarin anticoagulant therapy prior to admission (1.5-3.25 mg). After admission, patients were administered fresh frozen plasma and/or vitamin K1 to reverse anticoagulation. Out of the 16 patients (40%) who underwent surgical intervention, 4 died from cerebral hemorrhage deterioration during the hospital stay and did not restart anticoagulant therapy. Anticoagulant therapy was resumed within 3 days for 18 patients and more than three days after hemorrhage for the other 18 patients. After discharge, patients were followed up for 12 months or more. Unfortunately, during this period, 17% of patients (6/36) died. Conclusions: Definitive hemostatic measures can be as an important factor in the clinical resumption of anticoagulation. Halting anticoagulant therapy for 3 to 7 days may be safe. It is recommended that low molecular heparin be administered within 3 days as a bridge treatment, combine with warfarin anticoagulant therapy within 1 week after hemorrhage.

Combined laparoscopic-endoscopic approach for gastric glomus tumor: A case report.

BACKGROUND: Gastric glomus tumor (GGT) is rare submucosal mesenchymal tumor that lacks specific clinical manifestations and is usually treated mainly by traditional surgical resection. This paper presents a case of a GGT, exhibited both intraluminally and extraluminally growth that was removed by laparoscopy-gastroscopy cooperative surgery. CASE SUMMARY: A 52-year-old male presented with epigastric discomfort accompanied by a sense of fullness for 3 mo. Upper gastrointestinal endoscopy identified a submucosal lump located in the gastric antrum. Endoscopic ultrasonography identified a 2.4 cm × 1.8 cm lump located in the gastric antrum. It originated from the muscularis propria and exhibited both intraluminally and extraluminally growth, with hypoechoicity on the periphery, hyperechoicity in the middle, and unclear boundaries. Computed tomography showed nodular thickening of 3.0 cm × 2.2 cm in the gastric wall of the gastric antrum, and after enhancement, the lesion exhibited obvious enhancement We suspected that it was a gastrointestinal stromal tumor (glomus tumor and schwannoma were not excluded) and planned to perform laparoscopy-gastroscopy cooperative surgery. Immunohistochemical staining after the operation revealed that spinal muscular atrophy (+), h-caldesmon (+), cluster of differentiation 34 (CD34) (+), 2% Ki-67-positive rate, CD56, melanoma antigen, CD117, discovered on GIST-1, leukocyte common antigen, caudal type homeobox 2, cytokeratin, and S-100 were all negative. The tumor was finally diagnosed as a GGT. CONCLUSION: GGTs are rare submucosal tumors of the stomach and should be considered in the differential diagnosis of gastric submucosal tumors. Laparoscopy-gastroscopy cooperative surgery is less invasive and more precise and could be an effective method for the treatment of GGTs.

Determining cost-effectiveness of lung cancer screening in urban Chinese populations using a state-transition Markov model.

OBJECTIVES: This study analyses the cost-effectiveness of annual low-dose CT (LDCT) screening of high-risk cancer populations in Chinese urban areas. DESIGN: We used a Markov model to evaluate LDCT screening from a sociological perspective. SETTING: The data from two large lung cancer screening programmes in China were used. PARTICIPANTS: The sample consisted of 100 000 smokers who underwent annual LDCT screening until age 76. INTERVENTION: The study comprises five screening strategies, with the initial screening ages in both the screening strategies and their corresponding non-screening strategies being 40, 45, 50, 55 and 60 years, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER) between screening and non-screening strategies at the same initial age was evaluated. RESULTS: In the baseline scenario, compared with those who were not screened, the specific mortality from lung cancer decreased by 18.52%-23.13% among those who underwent screening. The ICER of LDCT screening ranges from US$13 056.82 to US$15 736.06 per quality-adjusted life year, which is greater than one but less than three times the gross domestic product per capita in China. An initial screening age of 55 years is the most cost-effective strategy. CONCLUSIONS: Baseline analysis shows that annual LDCT screening of heavy smokers in Chinese urban areas is likely to be cost-effective. The sensitivity analysis reveals that sensitivity, specificity and the overdiagnosis rate influence the cost-effectiveness of LDCT screening. All scenarios tested demonstrate cost-effectiveness, except for the combination of worst values of sensitivity, specificity and overdiagnosis. Therefore, the cost-effectiveness of a screening strategy depends on the performance of LDCT screenings.

Development and validation of an individual alternative splicing prognostic signature in gastric cancer.

Gastric cancer (GC) is a heterogeneous disease with different clinical manifestations and prognoses. Alternative splicing (AS) is a determinant of gene expression and contributes to protein diversity from a rather limited gene transcript in metazoans. AS events are associated with different aspects of cancer biology, including cell proliferation, apoptosis, invasion, etc. Here, we present a comprehensive analysis of the prognostic AS profile in GC. GC-specific AS (GCAS) events were analyzed, and overall survival-associated GCAS (OS-GCAS) events were verified among the genome-wide AS events identified in The Cancer Genome Atlas (TCGA) database. In total, 1,287 GCAS events of 837 genes and 173 OS-GCAS events of 130 genes were identified. The parental genes of OS-GCAS events were significantly enriched in the development of GC. Protein-protein interaction (PPI) and OS-GCAS-associated splicing factor (SF) interaction networks were constructed. Multivariate Cox regression analysis with least absolute shrinkage and selection operator (LASSO) penalty was performed to establish a prognostic risk formula, representing 23 OS-GCAS events. The low-risk group had better OS than the high-risk group and lower immune and stromal scores. Cox proportional hazard regression was applied to generate an AS-clinical integrated prognostic model with a considerable area under the curve (AUC) value in both the training and validation datasets. Our study provides a profile of OS-GCAS events and an AS-clinical nomogram to predict the prognosis of GC.

The Ratio of the Hemoglobin to Red Cell Distribution Width Combined with the Ratio of Platelets to Lymphocytes Can Predict the Survival of Patients with Gastric Cancer Liver Metastasis.

BACKGROUND: Hemoglobin/red cell distribution width (HR) and platelet/lymphocyte (PLR) ratios are considered effective prognostic markers in various cancers. We have proposed a new prognostic parameter: HR+PLR. The aim of this study is to explore the prognostic value of the HR+PLR scoring system in patients with gastric cancer liver metastasis. METHODS: This study retrospectively analyzed the clinical data of 306 patients with gastric cancer liver metastases admitted to our hospital from 2007 to 2014. According to the size of HR value and PLR value, we will divide the patients into three groups, namely, HR+PLR: (1) 0 points: HR > 1.02 and PLR < 128; (2) 1 point: HR > 1.02 and PLR > 128 and HR < 1.02 and PLR < 128; and (3) 2 points: HR < 1.02 and PLR > 128. RESULTS: The HR+PLR score was statistically different from age (P = 0.049), T stage (P < 0.001), N stage (P = 0.017), number of liver metastases (P = 0.018), gastrectomy (P < 0.001), hepatectomy (P = 0.001), peritoneal metastasis (P = 0.012), prognostic nutritional index (PNI) (P = 0.028), and neutrophil/lymphocyte ratio (NLR) (P = 0.045). The HR+PLR scoring system has a higher area under the ROC curve (AUC value) than PNI, PLR, HR, and PLR (AUC = 0.798, P < 0.001). In multivariate analysis, gastrectomy (P = 0.001), hepatectomy (P < 0.001), chemotherapy (P = 0.014), and HR+PLR score (P < 0.001) were considered independent prognostic factors. CONCLUSION: For patients with gastric cancer liver metastasis, the HR+PLR score is a simple, reliable, and economic prognostic marker.

The landscape of alternative splicing reveals novel events associated with tumorigenesis and the immune microenvironment in gastric cancer.

Alternative splicing (AS), contributing to vast protein diversity from a rather limited number of genes in eukaryotic transcripts, has emerged as an important signature for tumor initiation and progression. However, a systematic understanding of its functional impact and relevance to gastric cancer (GC) tumorigenesis is lacking. Differentially expressed AS (DEAS) was verified among GC-associated AS events based on RNA-seq profiles from the TCGA database. Functional enrichment analysis, unsupervised clustering analysis and prognostic models were used to infer the potential roles of DEAS events and their molecular, clinical and immune features. In total, 12,225 AS events were detected from 5,199 genes, among which 314 AS events were identified as DEAS events in GC. The parental genes of the DEAS events were significantly enriched in the regulation of GC-related processes. The splicing correlation network suggested a significant relationship between DEAS events and splicing factors (SFs). Three clusters of DEAS events were identified to be different in prognosis, cancer-specific signatures and immune features between distinct clusters. Univariate and multivariate analyses regarded 3 DEAS events as independent prognostic indicators. Profiling of the AS landscape in GC elucidated the functional roles of the splicing network in GC and might serve as a novel prognostic indicator and therapeutic target.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China.

BACKGROUND: Through analyzing the data from a single institution in Northeast China, this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer (GC). AIM: To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China, which is a high-prevalence area of GC. METHODS: The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital. The study mainly analyzed the data in three periods, 2000 to 2004 (Phase 1), 2005 to 2009 (Phase 2), and 2010 to 2014 (Phase 3). RESULTS: Over time, the postoperative survival rate significantly increased from 2000 to 2014. In the past 15 years, compared with Phases 1 and 2, the tumor size was smaller in Phase 3 (P < 0.001), but the proportion of high-medium differentiated tumors increased (P < 0.001). The proportion of early GC gradually increased from 3.9% to 14.4% (P < 0.001). A surprising improvement was observed in the mean number of retrieved lymph nodes, ranging from 11.4 to 27.5 (P < 0.001). The overall 5-year survival rate increased from 24% in Phase 1 to 43.8% in Phase 3. Through multivariate analysis, it was found that age, tumor size, histologic type, tumor-node-metastasis stage, depth of invasion, lymph node metastasis, surgical approach, local infiltration, radical extent, number of retrieved lymph nodes, and age group were independent risk factors that influenced the prognosis of patients with GC. CONCLUSION: The clinical features of GC in Northeast China changed during the observation period. The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.