UBE2L3 expression in human gastric cancer and its clinical significance.

PURPOSE: Gastric cancer (GC) is prevalent as one of the most common malignant tumors globally, with a particularly high incidence in China. The role of UBE2L3 in the initiation and progression of various cancers has been well documented, but its specific significance in GC is not yet fully elucidated. The objective of this study is to examine the expression and importance of UBE2L3 in human gastric cancer tissues. METHODS: Immunohistochemical staining and survival analysis were conducted on 125 cases of GC. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to assess the expression of UBE2L3 in GC cell lines. Cell lines with UBE2L3 knockdown and overexpression were cultured through lentivirus transfection and subsequently assessed using Western blot analysis. The involvement of UBE2L3 in the proliferation, invasion, and apoptosis of GC cells was confirmed through in vitro experiments, and its capacity to facilitate tumor growth was also validated in in vivo studies. RESULTS: The up-regulation of UBE2L3 expression was observed in GC, and its high expression was found to be significantly associated with the degree of differentiation (χ2 = 6.153, P = 0.0131), TNM stage (χ2 = 6.216, P = 0.0447), and poor overall survival. In vitro, UBE2L3 has been shown to enhance functions in GC cell lines, such as promoting proliferation and invasion, and inhibiting apoptosis. In vivo experiments have validated the role of UBE2L3 in promoting tumor growth. CONCLUSIONS: The findings of our study demonstrate the significant involvement of UBE2L3 in the pathogenesis and advancement of gastric cancer, suggesting its potential as a therapeutic target.

High expression of NOTCH2 in gastric adenocarcinoma: A novel early diagnostic target.

BACKGROUND AND AIM: NOTCH2 is overexpressed in gastric cancer (GC), and its enhanced activity is significantly correlated with worse tumor characteristics. We aim to analyze the clinicopathologic correlation between NOTCH2 and the molecular typing of GC by immunohistochemistry and by transcriptional sequencing. METHODS: In this immunohistochemical study, we detected NOTCH2, EBER, P53, HER2, MLH1, MSH2, PMS2, and MSH6 and evaluated the association of NOTCH2 with clinical and histopathological features in a large single-institutional series of gastric adenocarcinomas (n = 488). The correlation was also investigated between immunohistochemical results and survival outcomes. RESULTS: High NOTCH2 expression (2+/3+) was found in 139/488 (27.5%) samples analyzed. NOTCH2 expression was correlated with early stage T1 (P < 0.0001), GC in the fundus (P = 0.0364), and positive P53 status (P = 0.0019). We did not find an association between NOTCH2 and HER2, microsatellite instability, EBER, and overall survival. Through RNA sequencing, it was revealed that NOTCH2 plays an important biological function in the pathogenesis and development of GC. CONCLUSIONS: Our findings suggested that NOTCH2 may be a potential diagnostic target for GC due to the fact that its high expression is closely associated with the early stages of cancer.

A multidisciplinary collaborative diagnosis and rehabilitation program for dysphagia in general hospitals.

Dysphagia is a common complication of various clinical conditions, with an increased incidence as age advances. Complications such as aspiration, malnutrition, and aspiration pneumonia caused by dysphagia significantly affect the overall treatment outcomes of patients. Scholars both domestically and internationally are increasingly focusing on early rehabilitation for dysphagia. This article summarizes common conditions causing dysphagia, clinical manifestations, complications, screening assessment, diagnosis, rehabilitation, and nutritional support related to dysphagia. It emphasizes the arrival at a multidisciplinary collaborative diagnosis and formulation of a rehabilitation management plan for dysphagia in general hospitals in order to provide strategic suggestions for establishing a multidisciplinary collaborative model for swallowing disorder management in general hospitals.

Cemented vertebra and adjacent vertebra refractured in a chronic kidney disease-mineral and bone disorder patient: A case report.

BACKGROUND: Although percutaneous vertebral augmentation (PVA) is a commonly used procedure for treating vertebral compression fracture (VCF), the risk of vertebral refracture should be considered. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disease of mineral and bone metabolism. It is associated with an increased risk of fracture. Few studies have reported the use of PVA in patients with CKD-MBD. We herein report a rare case wherein the cemented vertebra and the adjacent vertebra refractured simultaneously in a CKD-MBD patient after PVA. CASE SUMMARY: A 74-year-old man suffered from low back pain after taking a fall about 3 wk ago. According to physical examination, imaging and laboratory findings, diagnoses of T12 VCF, CKD-MBD, and chronic kidney disease stage 5 were established. He then received percutaneous vertebroplasty at T12 vertebra. Fourteen weeks later, he presented with T12 and L1 vertebral refractures caused by lumbar sprain. Once again, he was given PVA which was optimized for the refractured vertebrae. Although the short-term postoperative effect was satisfactory, he reported chronic low back pain again at the 3-month follow-up. CONCLUSION: It is necessary that patients with CKD-MBD who have received PVA are aware of the adverse effects of CKD-MBD. It may increase the risk of vertebral refracture. Furthermore, the PVA surgical technique needs to be optimized according to the condition of the patient. The medium- and long-term effects of PVA remain uncertain in patients with CKD-MBD.

Cardiovascular MRI Reference Ranges for Heart, Aorta, and Pulmonary Artery in Healthy Chinese Children.

BACKGROUND: Cardiovascular magnetic resonance (cardiac MR) reference ranges in Chinese children are lacking. PURPOSE: To establish age- and sex-specific reference ranges for cardiac MR parameters in a cohort of healthy Chinese children. STUDY TYPE: Retrospective. SUBJECTS: One hundred ninety-six healthy children (mean age 9.5 ± 3.6 years, 111 boys). FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession. ASSESSMENT: Biventricular volume and ejection fractions (EF), left atrial (LA) volume, right atrial (RA) area, left ventricular (LV) mass and thickness, aortic root (AR), and main pulmonary artery (MPA) dimensions were measured. Parameters were compared between age groups and sex. The relationships between parameters and age, body mass index (BMI) and body surface area (BSA) were investigated. STATISTICAL TESTS: Independent-samples t tests; Pearson's correlation. A P value <0.05 was considered statistically significant. RESULTS: Generally, boys exhibited greater absolute measurements of LV volume (end-diastolic: 94.4 ± 29.5 vs. 81.3 ± 31.0 mL), LA volume (end-diastolic: 42.6 ± 13.4 vs. 38.0 ± 13.3 mL), RA area (end-diastolic: 11.6 ± 2.5 vs. 10.8 ± 2.6 cm2), LV thickness (base: 4.4 ± 1.1 vs. 3.8 ± 0.9 mm), AR dimensions (annuls: 16.3 ± 2.7 vs. 15.0 ± 2.8 mm), and MPA dimensions (14.3 ± 2.3 vs. 13.1 ± 2.4 mm) than girls did. However, these differences were not observed when the measurements were normalized to BSA (LV volume: 75.3 ± 11.7 vs. 71.9 ± 12.3 mL/m2, P = 0.052; LA volume: 34.8 ± 8.9 vs. 34.5 ± 7.6 mL/m2, P = 0.783; RA area: 9.7 ± 2.3 vs. 10.2 ± 2.3 cm2/m2, P = 0.107; LV thickness: 3.6 ± 0.7 vs. 3.6 ± 0.9 mm/m2, P = 0.990; AR: 13.6 ± 2.7 vs. 14.3 ± 3.4 mm/m2, P = 0.108; MPA: 11.9 ± 2.3 vs. 12.4 ± 2.4 mm/m2, P = 0.118). Boys had greater RV volume (end-diastolic: 98.7 ± 33.5 vs. 82.7 ± 33.1 mL) and LV mass (52.6 ± 20.2 vs. 41.4 ± 16.0 g) compared to girls, irrespective of whether the values were indexed or not for BSA. Additionally, there were significant associations between age, BMI, and BSA with biventricular volume, LA volume, RA area, LV mass and thickness, AR and MPA dimensions in both boys and girls. DATA CONCLUSION: This study suggests reference ranges at 1.5 T for Chinese children. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Relationship of serum total cholesterol and triglyceride with risk of mortality in maintenance hemodialysis patients: a multicenter prospective cohort study.

OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.

Temperature-Dependent Evaporative Anthropogenic VOC Emissions Significantly Exacerbate Regional Ozone Pollution.

The evaporative emissions of anthropogenic volatile organic compounds (AVOCs) are sensitive to ambient temperature. This sensitivity forms an air pollution-meteorology connection that has not been assessed on a regional scale. We parametrized the temperature dependence of evaporative AVOC fluxes in a regional air quality model and evaluated the impacts on surface ozone in the Beijing-Tianjin-Hebei (BTH) area of China during the summer of 2017. The temperature dependency of AVOC emissions drove an enhanced simulated ozone-temperature sensitivity of 1.0 to 1.8 µg m-3 K-1, comparable to the simulated ozone-temperature sensitivity driven by the temperature dependency of biogenic VOC emissions (1.7 to 2.4 µg m-3 K-1). Ozone enhancements driven by temperature-induced AVOC increases were localized to their point of emission and were relatively more important in urban areas than in rural regions. The inclusion of the temperature-dependent AVOC emissions in our model improved the simulated ozone-temperature sensitivities on days of ozone exceedance. Our results demonstrated the importance of temperature-dependent AVOC emissions on surface ozone pollution and its heretofore unrepresented role in air pollution-meteorology interactions.

Poly(Propylene Carbonate)-Based Biodegradable and Environment-Friendly Materials for Biomedical Applications.

Poly(propylene carbonate) (PPC) is an emerging "carbon fixation" polymer that holds the potential to become a "biomaterial of choice" in healthcare owing to its good biocompatibility, tunable biodegradability and safe degradation products. However, the commercialization and wide application of PPC as a biomedical material are still hindered by its narrow processing temperature range, poor mechanical properties and hydrophobic nature. Over recent decades, several physical, chemical and biological modifications of PPC have been achieved by introducing biocompatible polymers, inorganic ions or small molecules, which can endow PPC with better cytocompatibility and desirable biodegradability, and thus enable various applications. Indeed, a variety of PPC-based degradable materials have been used in medical applications including medical masks, surgical gowns, drug carriers, wound dressings, implants and scaffolds. In this review, the molecular structure, catalysts for synthesis, properties and modifications of PPC are discussed. Recent biomedical applications of PPC-based biomaterials are highlighted and summarized.

MicroRNA-18a prevents senescence of mesenchymal stem cells by targeting CTDSPL.

Stem cell therapy requires massive-scale homogeneous stem cells under strict qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in the premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renewal ability of MSCs. Over-expression of CTDSPL resulted in an enlarged morphology, up-regulation of p16 and accumulation of SA-ß-gal of MSCs. The reduced phosphorylated RB suggested cell cycle arrest of MSCs. All these results implied that CTDSPL induced premature senescence of MSCs. We further demonstrated that miR-18a-5p was a putative regulator of CTDSPL by luciferase reporter assay. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reducing ROS level, increased expression of Oct4 and Nanog, and promoted growth rate and differentiation capability. We reported for the first time that the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.

Bioequivalence Assessment of Two Dapoxetine Hydrochloride Formulations in Healthy Chinese Males Under Fasted and Fed Conditions.

This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single-center, 2-period, 2-sequence, randomized, open-label, self-crossover study with a washout period of 14 days, 30 in the fasted group and 30 in the fed group. Following a single 30-mg oral dose of the test or reference dapoxetine formulation, blood samples were collected before dosing to 72 hours after dosing. Liquid chromatography-tandem mass spectrometry was performed to measure plasma concentration of dapoxetine and determine pharmacokinetic parameters through noncompartmental analysis. The vital signs and adverse events were also monitored during the study. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last concentration time, and area under the plasma concentration-time curve from time 0 extrapolated to infinity of the 2 dapoxetine formulations completely fell within the regulatory criteria for bioequivalence of 80%-125%. In addition, both dapoxetine hydrochloride formulations were generally well tolerated. The generic dapoxetine hydrochloride tablet was bioequivalent to the marketed reference product in healthy Chinese men with no discernible safety differences.

Does competition support integrated care to improve quality?

Introduction: This work investigates the compatibility of integrated care and competition in China and analyses the impact of integrated care on regional care quality (DeptQ) within a competitive framework. Method: The study was built on multivariate correspondence analysis and a two-way fixed-effects model. The data were collected from Xiamen's Big Data Application Open Platform and represent nine specialised departments that regularly performed inter-institutional referrals between 2016 and 2019. Results: First, care quality for referred patients (ReferQ) and the relative scale of referred patients (ReferScale) and competition have an antagonistic but not completely mutually exclusive relationship. Second, ReferQ and competition both have a significant effect on DeptQ, but only when competition is weak can ReferQ and competition act synergistically on DeptQ. When competition is fierce, competition will weaken the impact of ReferQ on DeptQ. Conclusion: Changes in the intensity of integrated care and competition ultimately affect care quality.

Mesenchymal Stem Cells Target Gastric Cancer and Deliver Epirubicin via Tunneling Nanotubes for Enhanced Chemotherapy.

BACKGROUND: A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes. OBJECTIVE: Epirubicin delivery to gastric cancer cells using mesenchymal stem cells Methods: In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS. RESULTS: Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05). CONCLUSIONS: We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

A novel method for simultaneously measuring boronophenylalanine uptake in brain tumor cells and number of cells using inductively coupled plasma atomic emission spectroscopy.

Boron neutron capture therapy (BNCT) combines neutron irradiation with boron compounds that are selectively uptaken by tumor cells. Boronophenylalanine (BPA) is a boron compound used to treat malignant brain tumors. The determination of boron concentration in cells is of great relevance to the field of BNCT. This study was designed to develop a novel method for simultaneously measuring the uptake of BPA by U87 and U251 cells (two brain tumor cell lines) and number of cells using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results revealed a linear correlation between phosphorus intensity and the numbers of U87 and U251 cells, with correlation coefficients (R2) of 0.9995 and 0.9994, respectively. High accuracy and reliability of phosphorus concentration standard curve were also found. Using this new method, we found that BPA had no significant effect on phosphorus concentration in either U87 or U251 cells. However, BPA increased the boron concentration in U87 and U251 cells in a concentration-dependent manner, with the boron concentration in U87 cells being higher than that in U251 cells. In both U87 and U251 cells, boron was mainly distributed in the cytoplasm and nucleus, accounting for 85% and 13% of the total boron uptake by U87 cells and 86% and 11% of the total boron uptake by U251 cells, respectively. In the U87 and U251 cell-derived xenograft (CDX) animal model, tumor exhibited higher boron concentration values than blood, heart, liver, lung, and brain, with a tumor/blood ratio of 2.87 for U87 cells and 3.11 for U251 cells, respectively. These results suggest that the phosphorus concentration in U87 and U251 cells can represent the number of cells and BPA is easily uptaken by tumor cells as well as in tumor tissue.

Human Eye Activity Monitoring Using Continuous Wave Doppler Radar: A Feasibility Study.

Human eye activity has been widely studied in many fields such as psychology, neuroscience, medicine, and human-computer interaction engineering. In previous studies, monitoring of human eye activity mainly depends on electrooculogram (EOG) that requires a contact sensor. This article proposes a novel eye movement monitoring method called continuous wave doppler oculogram (cDOG). Unlike the conventional EOG-based eye movement monitoring methods, cDOG based on continuous wave doppler radar sensor (cDRS) can remotely measure human eye activity without placing electrodes on the head. To verify the feasibility of using cDOG for eye movement monitoring, we first theoretically analyzed the association between the radar signal and the corresponding eye movements measured with EOG. Afterward, we conducted an experiment to compare EOG and cDOG measurements under the conditions of eyes closure and opening. In addition, different eye movement states were considered, including right-left saccade, up-down saccade, eye-blink, and fixation. Several representative time domain and frequency domain features obtained from cDOG and from EOG were compared in these states, allowing us to demonstrate the feasibility of using cDOG for monitoring eye movements. The experimental results show that there is a correlation between cDOG and EOG in the time and frequency domain features, the average time error of single eye movement is less than 280.5 ms, and the accuracy of cDOG in eye movement detection is higher than 92.35%, when the distance between the cDRS and the face is 10 cm and eyes is facing the radar directly.

Modeling the Annexin A1-S100A11 heterotetramer: a molecular dynamics investigation of structure and correlated motion.

Annexin A1 (A1) has been shown to form a tetrameric complex (A1t) with S100A11 which is implicated in calcium homeostasis and EGFR pathways. In this work, a full-length model of the A1t was generated for the first time. Multiple molecular dynamics simulations were performed on the complete A1t model for several hundred nanoseconds each to assess the structure and dynamics of A1t. These simulations yielded three structures for the A1 N-terminus (ND) which were identified via principal component analysis. The orientations and interactions of the first 11 A1-ND residues for all three structures were conserved, and their binding modes were strikingly similar to those of the Annexin A2 N-terminus in the Annexin A2-p11 tetramer. In this study, we provided detailed atomistic information for the A1t. Strong interactions were identified within the A1t between the A1-ND and both S100A11 monomers. Residues M3, V4, S5, E6, L8, K9, W12, E15, and E18 of A1 were the strongest interactions between A1 and the S100A11 dimer. The different conformations of the A1t were attributed to the interaction between W12 of the A1-ND with M63 of S100A11 which caused a kink in the A1-ND. Cross-correlation analysis revealed strong correlated motion throughout the A1t. Strong positive correlation was observed between the ND and S100A11 in all simulations regardless of conformation. This work suggests that the stable binding of the first 11 residues of A1-ND to S100A11 is potentially a theme for Annexin-S100 complexes and that the flexibility of the A1-ND allows for multiple conformations of the A1t.Communicated by Ramaswamy H. Sarma.

Delta-radiomics features for predicting the major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

OBJECTIVES: To investigate if delta-radiomics features have the potential to predict the major pathological response (MPR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) patients. METHODS: Two hundred six stage IIA-IIIB NSCLC patients from three institutions (Database1 = 164; Database2 = 21; Database3 = 21) who received neoadjuvant chemoimmunotherapy and surgery were included. Patients in Database1 were randomly assigned to the training dataset and test dataset, with a ratio of 0.7:0.3. Patients in Database2 and Database3 were used as two independent external validation datasets. Contrast-enhanced CT scans were obtained at baseline and before surgery. The delta-radiomics features were defined as the relative net change of radiomics features between baseline and preoperative. The delta-radiomics model and pre-treatment radiomics model were established. The performance of Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) for predicting MPR was also evaluated. RESULTS: Half of the patients (106/206, 51.5%) showed MPR after neoadjuvant chemoimmunotherapy. For predicting MPR, the delta-radiomics model achieved a satisfying area under the curves (AUCs) values of 0.768, 0.732, 0.833, and 0.716 in the training, test, and two external validation databases, respectively, which showed a superior predictive performance than the pre-treatment radiomics model (0.644, 0.616, 0.475, and 0.608). Compared with iRECIST criteria (0.624, 0.572, 0.650, and 0.466), a mixed model that combines delta-radiomics features and iRECIST had higher AUC values for MPR prediction of 0.777, 0.761, 0.850, and 0.670 in four sets. CONCLUSION: The delta-radiomics model demonstrated superior diagnostic performance compared to pre-treatment radiomics model and iRECIST criteria in predicting MPR preoperatively in neoadjuvant chemoimmunotherapy for stage II-III NSCLC. CLINICAL RELEVANCE STATEMENT: Delta-radiomics features based on the relative net change of radiomics features between baseline and preoperative CT scans serve a vital support tool in accurately identifying responses to neoadjuvant chemoimmunotherapy, which can help physicians make more appropriate treatment decisions. KEY POINTS: • The performances of pre-treatment radiomics model and iRECIST model in predicting major pathological response of neoadjuvant chemoimmunotherapy were unsatisfactory. • The delta-radiomics features based on relative net change of radiomics features between baseline and preoperative CT scans may be used as a noninvasive biomarker for predicting major pathological response of neoadjuvant chemoimmunotherapy. • Combining delta-radiomics features and iRECIST can further improve the predictive performance of responses to neoadjuvant chemoimmunotherapy.

Real-time monitoring of glucose metabolism and effects of metformin on HepG2 cells using 13C in-cell NMR spectroscopy.

Metformin is currently a strong candidate antitumor agent for multiple cancers, and has the potential to inhibit cancer cell viability, growth, and proliferation. Metabolic reprogramming is a critical feature of cancer cells. However, the effects of metformin which targets glucose metabolism on HepG2 cancer cells remain unclear. In this study, to explore the effects of metformin on glucose metabolism in HepG2 cells, we conducted real-time metabolomic monitoring of live HepG2 cells treated with metformin using 13C in-cell NMR spectroscopy. Metabolic tracing with U-13C6-glucose revealed that metformin significantly increased the production of 13C-G3P and 13C-glycerol, which were reported to attenuate liver cancer development, but decreased the production of potential oncogenesis-supportive metabolites, including 13C-lactate, 13C-alanine, 13C-glycine, and 13C-glutamate. Moreover, the expression levels of enzymes associated with the measured metabolites were carried out. The results showed that the levels of ALT1, MCT4, GPD2 and MPC1 were greatly reduced, which were consistent with the changes of measured metabolites in 13C in-cell NMR spectroscopy. Overall, our approach directly provides fundamental insights into the effects of metformin on glucose metabolism in live HepG2 cells, and highlights the potential mechanism of metformin, including the increase in production of G3P and glycerol derived from glucose, as well as the inhibition of glucose incorporation into lactate, alanine, glutamate, and glycine.

Epidemiology, risk areas and macro determinants of gastric cancer: a study based on geospatial analysis.

BACKGROUND: Both incidence and mortality of gastric cancer in Gansu rank first in china, this study aimed to describe the recent prevalence of gastric cancer and explore the social and environmental determinants of gastric cancer in Gansu Province. METHODS: The incidence of gastric cancer in each city of Gansu Province was calculated by utilizing clinical data from patients with gastric cancer (2013-2021) sourced from the medical big data platform of the Gansu Province Health Commission, and demographic data provided by the Gansu Province Bureau of Statistics. Subsequently, we conducted joinpoint regression analysis, spatial auto-correlation analysis, space-time scanning analysis, as well as an exploration into the correlation between social and environmental factors and GC incidence in Gansu Province with Joinpoint_5.0, ArcGIS_10.8, GeoDa, SaTScanTM_10.1.1 and GeoDetector_2018. RESULTS: A total of 75,522 cases of gastric cancer were included in this study. Our findings suggested a significant upward trend in the incidence of gastric cancer over the past nine years. Notably, Wuwei, Zhangye and Jinchang had the highest incidence rates while Longnan, Qingyang and Jiayuguan had the lowest. In spatial analysis, we have identified significant high-high cluster areas and delineated two high-risk regions as well as one low-risk region for gastric cancer in Gansu. Furthermore, our findings suggested that several social and environmental determinants such as medical resource allocation, regional economic development and climate conditions exerted significant influence on the incidence of gastric cancer. CONCLUSIONS: Gastric cancer remains an enormous threat to people in Gansu Province, the significant risk areas, social and environmental determinants were observed in this study, which may improve our understanding of gastric cancer epidemiology and help guide public health interventions in Gansu Province.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature.

BACKGROUND: To evaluate the clinicopathological features and prognosis of gastric cancer (GC) occurring synchronously with gastrointestinal stromal tumor (GIST). CASE SUMMARY: We report 19 patients with concurrent GC and GIST (17 male and 2 female, median age 62 years). GC was most often located in the lower third of the stomach. GIST was diagnosed preoperatively in four patients. GIST was most often located in the gastric body (n = 8, 42%). The most common growth pattern in GIST was extraluminal (n = 12, 63%). The positive expression rates of CD117 and CD34 in GIST were 100% and 95%, respectively. Most patients with GIST (n = 17, 89%) were very low or low risk. There was no recurrence of GIST during follow-up. The 3-year cumulative survival rate was 73.9%, and the 5-year cumulative survival rate was 59.2%. The combined analysis of this study and literature reports (47 reports, 157 patients) found that GC and GIST were usually located in the lower third (42%) and middle third (51%) of the stomach. GC was usually early (stage I: 42%), poorly differentiated (42%) intestinal-type adenocarcinoma (51%). GISTs were primarily small in diameter (median: 1.2 cm) and very low or low risk (89%). CONCLUSION: Synchronous GC and GIST may not be rare. They have specific clinicopathological characteristics, and may have mutual inhibition in pathogenesis and progression.