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.

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.

Multimodality imaging assessment of primary pericardial rhabdomyosarcoma: a case report.

Primary pericardial sarcomas are rare and lethal diseases. To date, only a few cases of primary pericardial sarcomas, such as rhabdomyosarcoma (RMS), have been reported. Since the unusual location of RMS in the pericardium makes it challenging to diagnose, precise diagnostic procedures are required. In this study, we present the case of a 23-year-old man who experienced postprandial obstruction and atypical precordial pain that lasted for a week. Echocardiography revealed a heterogeneous isoechoic pericardial mass with a significant pericardial effusion. Contrast-enhanced CT revealed a massive pericardial effusion along with an irregular, defined, heterogeneously enhancing mass that was located between the pericardium and diaphragm. PET-CT imaging showed an intense FDG uptake in the pericardial mass. Furthermore, cardiac MRI demonstrated malignant characteristics of the pericardial mass and provided a detailed visualization of its exact anatomical connection with both cardiac and extracardiac structures. Finally, a pathologic examination of a puncture biopsy specimen confirmed the diagnosis of primary pericardial RMS. Our case emphasizes the importance of multimodal imaging for the differential diagnosis and evaluation of cardiac involvement, while providing clinicians with crucial information for clinical treatment and decision-making.

Using nomogram, decision tree, and deep learning models to predict lymph node metastasis in patients with early gastric cancer: a multi-cohort study.

The accurate assessment of lymph node metastasis (LNM) in patients with early gastric cancer is critical to the selection of the most appropriate surgical treatment. This study aims to develop an optimal LNM prediction model using different methods, including nomogram, Decision Tree, Naive Bayes, and deep learning methods. In this study, we included two independent datasets: the gastrectomy set (n=3158) and the endoscopic submucosal dissection (ESD) set (n=323). The nomogram, Decision Tree, Naive Bayes, and fully convolutional neural networks (FCNN) models were established based on logistic regression analysis of the development set. The predictive power of the LNM prediction models was revealed by time-dependent receiver operating characteristic (ROC) curves and calibration plots. We then used the ESD set as an external cohort to evaluate the models' performance. In the gastrectomy set, multivariate analysis showed that gender (P=0.008), year when diagnosed (2006-2010 year, P=0.265; 2011-2015 year, P=0.001; and 2016-2020 year, P<0.001, respectively), tumor size (2-4 cm, P=0.001; and ≥4 cm, P<0.001, respectively), tumor grade (poorly-moderately, P=0.016; moderately, P<0.001; well-moderately, P<0.001; and well, P<0.001, respectively), vascular invasion (P<0.001), and pT stage (P<0.001) were independent risk factors for LNM in early gastric cancer. The area under the curve (AUC) for the validation set using the nomogram, Decision Tree, Naive Bayes, and FCNN models were 0.78, 0.76, 0.77, and 0.79, respectively. In conclusion, our multi-cohort study systematically investigated different LNM prediction methods for patients with early gastric cancer. These models were validated and shown to be reliable with AUC>0.76 for all. Specifically, the FCNN model showed the most accurate prediction of LNM risks in early gastric cancer patients with AUC=0.79. Based on the FCNN model, patients with LNM rates of >4.77% are strong candidates for gastrectomy rather than ESD surgery.

Longitudinal Assessment of Chest CT Findings and Pulmonary Function after COVID-19 Infection.

Background Information on pulmonary sequelae and pulmonary function 2 years after recovery from SARS-CoV-2 infection is lacking. Purpose To longitudinally assess changes in chest CT abnormalities and pulmonary function in individuals after SARS-CoV-2 infection. Materials and Methods In this prospective study, participants discharged from the hospital after SARS-CoV-2 infection from January 20 to March 10, 2020, were considered for enrollment. Participants without chest CT scans at admission or with complete resolution of lung abnormalities at discharge were excluded. Serial chest CT scans and pulmonary function test results were obtained 6 months (June 20 to August 31, 2020), 12 months (December 20, 2020, to February 3, 2021), and 2 years (November 16, 2021, to January 10, 2022) after symptom onset. The term interstitial lung abnormality (ILA) and two subcategories, fibrotic ILAs and nonfibrotic ILAs, were used to describe residual CT abnormalities on follow-up CT scans. Differences between groups were compared with the χ2 test, Fisher exact test, or independent samples t test. Results Overall, 144 participants (median age, 60 years [range, 27-80 years]; 79 men) were included. On 2-year follow-up CT scans, 39% of participants (56 of 144) had ILAs, including 23% (33 of 144) with fibrotic ILAs and 16% (23 of 144) with nonfibrotic ILAs. The remaining 88 of 144 participants (61%) showed complete radiologic resolution. Over 2 years, the incidence of ILAs gradually decreased (54%, 42%, and 39% of participants at 6 months, 12 months, and 2 years, respectively; P < .001). Respiratory symptoms (34% vs 15%, P = .007) and abnormal diffusing capacity of lung for carbon monoxide (43% vs 20%, P = .004) occurred more frequently in participants with ILAs than in those with complete radiologic resolution. Conclusion More than one-third of participants had persistent interstitial lung abnormalities 2 years after COVID-19 infection, which were associated with respiratory symptoms and decreased diffusion pulmonary function. Chinese Clinical Trial Registry no. ChiCTR2000038609 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by van Beek in this issue.

Obstacles and Coping Strategies of CAR-T Cell Immunotherapy in Solid Tumors.

Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.

Impacts of Chemical Degradation on the Global Budget of Atmospheric Levoglucosan and Its Use As a Biomass Burning Tracer.

Levoglucosan has been widely used to quantitatively assess biomass burning's contribution to ambient aerosols, but previous such assessments have not accounted for levoglucosan's degradation in the atmosphere. We develop the first global simulation of atmospheric levoglucosan, explicitly accounting for its chemical degradation, to evaluate the impacts on levoglucosan's use in quantitative aerosol source apportionment. Levoglucosan is emitted into the atmosphere from the burning of plant matter in open fires (1.7 Tg yr-1) and as biofuels (2.1 Tg yr-1). Sinks of atmospheric levoglucosan include aqueous-phase oxidation (2.9 Tg yr-1), heterogeneous oxidation (0.16 Tg yr-1), gas-phase oxidation (1.4 × 10-4 Tg yr-1), and dry and wet deposition (0.27 and 0.43 Tg yr -1). The global atmospheric burden of levoglucosan is 19 Gg with a lifetime of 1.8 days. Observations show a sharp decline in levoglucosan's concentrations and its relative abundance to organic carbon aerosol (OC) and particulate K+ from near-source to remote sites. We show that such features can only be reproduced when levoglucosan's chemical degradation is included in the model. Using model results, we develop statistical parametrizations to account for the atmospheric degradation in levoglucosan measurements, improving their use for quantitative aerosol source apportionment.

Assessment of regional left ventricular myocardial strain in patients with left anterior descending coronary stenosis using computed tomography feature tracking.

BACKGROUND: Computed tomography feature tracking (CT-FT) has emerged as a valuable method for the assessment of cardiac function. However, no studies have investigated the usefulness of CT-derived assessments of left ventricular (LV) strain in coronary artery disease (CAD). Our aim was to evaluate regional LV systolic deformation in patients with left anterior descending coronary artery (LAD) stenosis using CT-FT. METHODS: Seventy-six patients with LAD stenosis were enrolled. The patients were divided into four groups according to the percentage of LAD stenosis: ≤25% was defined as group I (24 patients), 26 to 49% as group II (17 patients), 50 to 74% as group III (21 patients), and ≥ 75% as group IV (14 patients). Thirty-two sex- and age-matched healthy subjects were included as controls. RESULTS: No intergroup differences were found between groups I-IV and the controls in terms of the left ventricular ejection fraction, end-diastolic volume and end-systolic volume. However, the longitudinal strain (LS) of the LAD territory was significantly reduced in groups I-IV compared with the controls (- 20.8, - 18.6%, - 18.6%, and - 17.0% vs - 23.7%, respectively). The circumferential strain (CS) of the LAD territory was significantly reduced in groups III and IV compared with the controls and groups I and II (- 22.4% and - 22.1% vs - 25.4, - 24.1%, and - 25.3%, respectively). Compared with the non-LAD territory, the LAD territory in groups II-IV showed significantly increased LS (- 18.6% vs - 21.9%, p = 0.07; - 18.6% vs - 21.9%, p = 0.024; - 17.5% vs - 20%, p = 0.032, respectively). The severity of LAD stenosis was positively correlated with the LS of the LAD territory (r = 0.438, p = 0.002). CONCLUSION: CT-FT can detect decreasing LV systolic function in patients with LAD stenosis. LV regional systolic deformation of the LAD territory was reduced with increasing LAD stenosis severity.

Health outcomes in offspring of mother with breast implants: A protocol of systematic review and meta-analysis.

BACKGROUND: An increasing number of women undergo breast augmentation at their reproductive age. The most existing evidence focuses on the impact of breast implant on the index women's health and breastfeeding after they give birth to a child. No previous systematic review has investigated the association between breast implant in mother and health outcomes in offspring. In this study, we aimed to conduct a systematic review and meta-analysis to evaluate the influence of breast implant on offspring's health outcomes. METHODS: A comprehensive search strategy will be conducted including the following databases: MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wan Fang Data. The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) will be searched as well for retrieving the ongoing studies. The cohort study and case-control study will be considered as eligible study if investigating the impact of breast implant in mother on health outcomes in offspring. The risk of bias of included studies will be appraised by the Newcastle-Ottawa scale. RESULTS: The results of this study will be presented in the full-text of the systematic review. CONCLUSION: This systematic review and meta-analysis will infer a conclusion on the association between breast implant in mother and health outcomes in offspring, and the quality of existing evidence.PROSPERO registration number: CRD42019121221.

Comprehensive assessment gene signatures for clear cell renal cell carcinoma prognosis.

There are many prognostic gene signature models in clear cell renal cell carcinoma (ccRCC). However, different results from various methods and samples are hard to contribute to clinical practice. It is necessary to develop a robust gene signature for improving clinical practice in ccRCC.A method was proposed to integrate least absolute shrinkage and selection operator and multiple Cox regression to obtain mRNA and microRNA signature from the cancer genomic atlas database for predicting prognosis of ccRCC. The gene signature model consisted by 5 mRNAs and 1 microRNA was identified. Prognosis index (PI) model was constructed from RNA expression and median value of PI is used to classified patients into high- and low-risk groups.The results showed that high-risk patients showed significantly decrease survival comparison with low-risk groups [hazard ratio (HR) =7.13, 95% confidence interval = 3.71-13.70, P < .001]. As the gene signature was mainly consisted by mRNA, the validation data can use transcriptomic data to verify. For comparison of the performance with previous works, other gene signature models and 4 datasets of ccRCC were retrieved from publications and public database. For estimating PI in each model, 3 indicators including HR, concordance index , and the area under the curve of receiver operating characteristic for 3 years were calculated across 4 independent datasets.The comparison results showed that the integrative model from our study was more robust than other models via comprehensive analysis. These findings provide some genes for further study their functions and mechanisms in ccRCC tumorigenesis and malignance, and may be useful for effective clinical decision making of ccRCC patients.

Frey procedure for chronic pancreatitis: Evidence-based assessment of short- and long-term results in comparison to pancreatoduodenectomy and Beger procedure: A meta-analysis.

BACKGROUND AND OBJECTIVE: Patients with chronic pancreatitis often require surgical treatment. The aim of this study was to evaluate the published evidence for Frey procedure in patients with chronic pancreatitis. METHODS: Literature search was undertaken to identify eligible studies until February 2015. Using meta-analytical techniques, Frey procedure was compared with pancreatoduodenectomy or Beger procedure, and the short- and long-term outcomes were analysed. RESULTS: Twenty-three studies comprising a total of 800 patients were reviewed. The postoperative morbidity and mortality were 23.2% and 0.4% respectively. The percentage of postoperative pain-relief patients was 89.4%. New onset of diabetes and exocrine insufficiency was present in 17.3% and 30.7% of patients, respectively. Compared with pancreatoduodenectomy, Frey procedure had favorable outcomes in terms of operation time, blood transfusion, overall morbidity, length of hospital and intensive care unit stay, pancreatic function and quality of life. Compared with Beger procedure, Frey procedure had shorter operation time and lower morbidity. CONCLUSIONS: Frey procedure is a safe and effective surgical procedure for chronic pancreatitis with dilated duct in the absence of neoplasia.