Research progress and future directions of immune checkpoint inhibitor combination therapy in advanced gastric cancer.

In recent years, with the continuous development of molecular immunology, immune checkpoint inhibitors (ICIs) have also been widely used in the treatment of gastric cancer, but they still face some challenges: The first is that only some people can benefit, the second is the treatment-related adverse events (TRAEs) that occur during treatment, and the third is the emergence of varying degrees of drug resistance with long-term use. How to overcome these challenges, combined therapy based on ICIs has become one of the important strategies. This article summarizes the clinical application of ICIs combined with chemotherapy, targeted therapy, radiotherapy, photodynamic therapy, thermotherapy, immune adjuvant, and dual immunotherapy and discusses the mechanism, and also summarizes the advantages and disadvantages of the current combination modalities and the potential research value. The aim of this study is to provide more and more optimized combination regimen for ICI combined therapy in patients with advanced gastric cancer and to provide reference for clinical and scientific research.

Does ambient particulate matter 1 increase the risk of gastric cancer in the northwest of China?

Gastric cancer (GC) remains a significant health concern in Gansu province, China, with morbidity and mortality rates surpassing national averages. Despite the recognized health risks associated with ambient particulate matter with an aerodynamic diameter <1 µm (PM1), the relationship between PM1 exposure and GC incidence has not been extensively studied. Data on GC cases from 2013 to 2021 were gathered from 262 hospitals in Gansu, China. Concurrently, data on the normalized vegetation index (NDVI), gross domestic product (GDP), drinking and smoking behavioral index (DSBI), PM1, PM2.5, and PM2.5-1 were collected. Utilizing a Bayesian conditional autoregressive (CAR) combined generalized linear model (GLM) with quasi-Poisson regression, we evaluated the impact of PM1, PM2.5, PM2.5-1, NDVI, DSBI, and GDP on GC morbidity while adjusting for potential confounders. Our analysis indicated that exposure to PM1 (µg/m3) is significantly positively correlated with GC incidence in regions with an overall age-standardized incidence rate (ASIR) >40 (relative risks [RR]: 1.023, 95% confidence intervals [CI, 1.007, 1.039]), male ASIR >50 (RR: 1.014, 95% CI [1.009, 1.019]), and female ASIR >20 (RR: 1.010, 95% CI [1.002, 1.018]). PM2.5, PM2.5-1, DSBI, and GDP were positively correlated with GC incidence, while NDVI was negatively correlated in the study regions. Our findings provided evidence of a positive correlation between PM1 exposure and GC incidence in high-risk areas of GC within arid regions. Further research is warranted to elucidate the complex nonlinear relationships between environmental factors and GC. These insights could inform strategies for improving the control and prevention of GC in Gansu and similar regions.

Impact of Diabetes on Persistent Radiological Abnormalities and Pulmonary Diffusion Dysfunction in COVID-19 Survivors: A 3-Year Prospective Cohort Study.

RATIONALE AND OBJECTIVES: Little is known about the long-term impact of diabetes on lung impairment in COVID-19 survivors over a three-year period. This study evaluated the long-term impact of diabetes on persistent radiological pulmonary abnormalities and lung function impairment in COVID-19 survivors over three years. MATERIALS AND METHODS: In this prospective, multicenter, cohort study, pulmonary sequelae were compared between COVID-19 survivors with and without diabetes. Serial chest CT scans, symptom questionnaires and pulmonary function tests were obtained 6 months, 12 months, 2 years and 3 years post-discharge. The independent predictors for lung dysfunction at the 3-year follow-up were analyzed. RESULTS: A total of 278 COVID-19 survivors (63 [IQR 57-69] year-old, female: 103 [37.0%]) were included. At the 3-year follow-up, individuals in the diabetes group had higher incidences of respiratory symptoms, radiological pulmonary abnormalities and pulmonary diffusion dysfunction than those in the control group. Diabetes (OR: 2.18, 95% CI: 1.04-4.59, p = 0.034), allergy (OR: 2.26, 95% CI: 1.09-4.74, p = 0.029), female (OR: 2.70, 95% CI: 1.37-5.29, p = 0.004), severe COVID-19 (OR: 4.10, 95% CI: 1.54-10.93, p = 0.005), and fibrotic-like CT changes (OR: 5.64, 95% CI: 2.28-13.98, p < 0.001) were independent predictors of pulmonary diffusion dysfunction in COVID-19 survivors. CONCLUSION: These results highlight the long-term deleterious effect of diabetes status on radiological pulmonary abnormalities and pulmonary dysfunction in COVID-19 survivors. This study provides important evidence support for long-term monitoring of lung abnormalities in COVID-19 recovery survivors with diabetes.

Predictive value of delta-radiomic features for prognosis of advanced non-small cell lung cancer patients undergoing immune checkpoint inhibitor therapy.

Background: No robust predictive biomarkers exist to identify non-small cell lung cancer (NSCLC) patients likely to benefit from immune checkpoint inhibitor (ICI) therapies. The aim of this study was to explore the role of delta-radiomics features in predicting the clinical outcomes of patients with advanced NSCLC who received ICI therapy. Methods: Data of 179 patients with advanced NSCLC (stages IIIB-IV) from two institutions (Database 1 =133; Database 2 =46) were retrospectively analyzed. Patients in the Database 1 were randomly assigned into training and validation dataset, with a ratio of 8:2. Patients in Database 2 were allocated into testing dataset. Features were selected from computed tomography (CT) images before and 6-8 weeks after ICI therapy. For each lesion, a total of 1,037 radiomic features were extracted. Lowly reliable [intraclass correlation coefficient (ICC) <0.8] and redundant (r>0.8) features were excluded. The delta-radiomics features were defined as the relative net change of radiomics features between two time points. Prognostic models for progression-free survival (PFS) and overall survival (OS) were established using the multivariate Cox regression based on selected delta-radiomics features. A clinical model and a pre-treatment radiomics model were established as well. Results: The median PFS (after therapy) was 7.0 [interquartile range (IQR): 3.4, 9.1] (range, 1.4-13.2) months. To predict PFS, the model established based on the five most contributing delta-radiomics features yielded Harrell's concordance index (C-index) values of 0.708, 0.688, and 0.603 in the training, validation, and testing databases, respectively. The median survival time was 12 (IQR: 8.7, 15.8) (range, 2.9-23.3) months. To predict OS, a promising prognostic performance was confirmed with the corresponding C-index values of 0.810, 0.762, and 0.697 in the three datasets based on the seven most contributing delta-radiomics features, respectively. Furthermore, compared with clinical and pre-treatment radiomics models, the delta-radiomics model had the highest area under the curve (AUC) value and the best patients' stratification ability. Conclusions: The delta-radiomics model showed a good performance in predicting therapeutic outcomes in advanced NSCLC patients undergoing ICI therapy. It provides a higher predictive value than clinical and the pre-treatment radiomics models.

Establishment and validation of a novel CD8+ T cell-associated prognostic signature for predicting clinical outcomes and immunotherapy response in hepatocellular carcinoma via integrating single-cell RNA-seq and bulk RNA-seq.

CD8+ T lymphocytes are critical in the immune response against neoplasms, yet the prognostic relevance of CD8+ T cell-associated genes in hepatocellular carcinoma (HCC) is not fully understood. We sourced single-cell RNA-sequencing (scRNA-seq) and bulk RNA-seq data for HCC from the GSE98638 dataset and The Cancer Genome Atlas (TCGA) repository. We utilized Weighted Gene Correlation Network Analysis (WGCNA) to identify CD8+ T cell-related genes. A clinical prognostic model for risk stratification was then constructed via Cox-Lasso regression analysis. The Immunophenotypic Score (IPS) was utilized to evaluate the potential of immunotherapeutic interventions in the categorized cohorts. Validation of the expression of CD8+ T cell-associated risk genes was performed using quantitative reverse transcription PCR (qRT-PCR). Integrating scRNA-seq with RNA-seq data, we identified five CD8+ T cell-related signature genes: IKBKE, ATP1B3, MSC, ADA, and BATF. Notably, HCC patients in the high-risk group had markedly decreased overall survival. Elevated infiltration levels of CD8+ T cells, B cells, and macrophages were observed in the high-risk group. Moreover, there was a positive correlation between the risk score and immune checkpoints (ICPs), including PDCD1, CD274, and CTLA4. Patients within the high-risk group subject to PD1 and CTLA4 blockade exhibited higher IPS levels. Additionally, the expression of the five risk genes was upregulated in HCC cell lines and tissues compared to normal cells and tissues. Our findings establish a prognostic signature based on CD8+ T cells, offering a potent predictive model for clinical outcomes and responsiveness to immunotherapy in HCC patients.

Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair.

Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

A qualitative study on inner experience of self-management behavior among elderly patients with type 2 diabetes in rural areas.

BACKGROUND: As a chronic metabolic disease, diabetes poses a serious threat to human health and has become a major public health problem in China and worldwide. In 2020, 30% of Chinese people (aged ≥ 60 years) reported having diabetes mellitus. Moreover, individuals with diabetes living in rural areas face a significantly higher mortality risk compared to those in urban areas. In this study, we explored the inner experience of self-management behaviors in elderly patients with type 2 diabetes in rural areas to inform targeted interventions. METHODS: A phenomenological research design was used to explore the inner experience of self-management in rural elderly diabetes. Ten elderly diabetic patients were sampled from December 2022 to March 2023 in rural areas of Yangcheng County, Jincheng City, ShanXi Province, China. The seven-step Colaizzi phenomenological was used to analyze the interview data and generate themes. RESULTS: Four themes emerged: "Insufficient self-management cognition", "Negative self-management attitude", "Slack self-management behavior", and "No time for self-management". CONCLUSION: The level of self-management among elderly patients with type 2 diabetes in rural areas is low. Healthcare professionals should develop targeted interventions aimed at enhancing their cognitive levels, modifying their coping styles, and improving their self-management abilities to improve their quality of life.

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.

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.

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.

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.

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.

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.

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.

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.