Conventional versus rubber band traction-assisted endoscopic submucosal dissection for rectal neuroendocrine tumors: a single-center retrospective study (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is a safe and effective technique for the treatment of gastrointestinal tumors, including rectal neuroendocrine tumors (r-NETs). However, the relative advantages of traction-assisted ESD for the treatment of small rectal lesions are still debated. AIMS: We conducted a study to compare the efficacy and safety of rubber band traction-assisted ESD (RBT-ESD) to conventional ESD (C-ESD). METHODS: This study retrospectively analyzed consecutive patients with r-NET treated with ESD between October 2021 and October 2023. Our study assessed differences between the groups in the complete resection rate of lesions, muscular layer injury, surgical complications, operation time, resection speed, time to liquid diet, postoperative hospital stay, hospital cost, and recurrence rate. RESULTS: A total of 119 patients with r-NETs participated in this study (RBT-ESD group, n = 27; C-ESD group, n = 92). The operation time in RBT-ESD group was shorter than in C-ESD group, but the difference was not statistically significant (16.0 min [9.0-22.0 min] vs. 18.0 min [13.3-27.0 min], P = 0.056). However, the resection speed was significantly faster in the RBT-ESD group (6.7 vs. 4.1 mm2/min, P = 0.005). Furthermore, the RBT-ESD group showed significantly less muscular layer injury (P = 0.047) and faster diet recovery (P = 0.035). No significant differences were observed in the complete resection rate, surgical complications, postoperative hospital stay, hospital cost, or recurrence rate between the two groups. CONCLUSION: For r-NETs of < 2 cm in size, the RBT method did not significantly shorten the operation time but resulted in faster resection speed, less muscular layer injury, and earlier postoperative recovery to a liquid diet.

Revealing spatiotemporal inequalities, hotspots, and determinants in healthcare resource distribution: insights from hospital beds panel data in 2308 Chinese counties.

BACKGROUND: Ensuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants. METHODS: To demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years' worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors' spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI). RESULTS: Spatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84-42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80-63.83%). Factors' space-scale variation explained 75.71% (68.94-81.55%), whereas time-scale variation contributed 20.25% (14.14-27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations. CONCLUSIONS: Three-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.

The Role of OH Cards in Psychological Interventions for Children With Fractures.

Context: Fractures are traumatic events, with psychological effects that can have a negative impact on children hospitalized with fractures. They can seriously affect children's physical rehabilitation and quality of life and even produce psychological disorders The OH card is a metaphorical card that allows access to an individual's inner world and can have a positive effect in psychotherapy. Objective: The study intended to investigate the use of OH Cards during psychological interventions with children with fractures and to provide a methodological reference for the use of OH Cards in therapy. Design: The research team performed a randomized controlled study. Setting: The study took place in the Department of Trauma Surgery at Children's Hospital of Hebei Province in Shijiazhuang, China. Participants: Participants were 74 children with fractures who had been admitted to the hospital between September 2020 and November 2021. Intervention: The research team randomly divided participants into two groups using a random number table: (1) 37 in the intervention group, who received a conventional nursing intervention and also an OH-card intervention, and (2) 37 in the control group, who received conventional nursing interventions only. Outcome Measures: At baseline and postintervention, the research team: (1) measured the participants' posttraumatic growth scores, using the children's version of the Post-Traumatic Growth Inventory (PTGI); (2) assessed their coping styles, using the Medical Coping Modes Questionnaire (MCMQ); (3) determined the existence of any stress disorders, using the Child Stress Disorder Checklist (CSDC); (4) evaluated their mental statuses using the Depression Self-Rating Scale (DSRSC) and the Screen for Child Anxiety-related Emotional Disorders (SCARED); and (5) measured participants' Fracture Knowledge Questionnaire scores. Results: At baseline, no significant differences existed between the groups for any outcome measure at baseline. Postintervention, the intervention group's scores: (1) on the PTGI, were significantly higher for mental change, appreciate life, individual force, new possibilities and personal relation than those of the control group; (2) on the MCMQ, were significantly higher for facing and significantly lower for avoidance and yield than those of the control group; (3) on the CSDC, were significantly lower for trauma incidents and acute response than the control group did; (4) on the DSRSC were significantly lower and on SCARED were significantly higher than those of the control group; and (5) on the Fracture Knowledge Questionnaire were significantly higher than those of the control group. Conclusions: OH Cards can increase the posttraumatic growth scores of children with fractures, improve their coping styles, reduce stress disorders, decrease depression and improve their psychological state, increase their knowledge about fractures, and promote their recovery.

LC-MS/MS determination of buparlisib, a phosphoinositide 3 kinase inhibitor in rat plasma: Application to a pharmacokinetic study.

Buparlisib is a selective phosphoinositide 3 kinase inhibitor currently evaluated in clinical trials. We developed and validated an LC-MS/MS coupled with a one-step protein precipitation extraction method for the quantitation of buparlisib in rat plasma. After protein precipitation with acetonitrile, the plasma sample was analyzed using a Cortecs UPLC C18 column, with acetonitrile-0.1% formic acid as the mobile phase system. Mass spectrometric detection was conducted in positive ionization mode, with target quantitative ion pair of m/z 411.2 → 367.2 for buparlisib. The calibration curve showed good linearity (1.0-3000 ng/ml), with acceptable accuracy (RE ranging from -6.2 to 5.9%) and precision (RSD within 8.2%) values at quality control concentrations. Extraction recovery from plasma was 80.9-88.7% and the matrix effect was negligible (92.6-95.2%). The validated method presented a simple quantification method of buparlisib in detail and utilized it for a pharmacokinetic study at three dose concentrations after oral administration in Wistar rats.

Highly efficient soluble expression and purification of recombinant human basic fibroblast growth factor (hbFGF) by fusion with a new collagen-like protein (Scl2) in Escherichia coli.

Human basic fibroblast growth factor (hbFGF) is involved in a wide range of biological activities that affect the growth, differentiation, and migration. Due to its wound healing effects and therapy, hbFGF has the potential as therapeutic agent. Therefore, large-scale production of biologically active recombinant hbFGF with low cost is highly desirable. However, the complex structure of hbFGF hinders its high-level expression as the soluble and functional form. In the present study, an efficient, cost-effective, and scalable method for producing recombinant hbFGF was developed. The modified collagen-like protein (Scl2-M) from Streptococcus pyogenes was used as the fusion tag for producing recombinant hbFGF for the first time. After optimization, the expression level of Scl2-M-hbFGF reached approximately 0.85 g/L in the shake flask and 7.7 g/L in a high cell-density fermenter using glycerol as a carbon source. Then, the recombinant Scl2-M-hbFGF was readily purified using one-step acid precipitation and the purified Scl2-M-hbFGF was digested with enterokinase. The digested mixture was further subject to ion-exchange chromatography, and the final high-purity (96%) hbFGF product was prepared by freeze-drying. The recovery rate of the whole purification process attained 55.0%. In addition, the biological activity of recombinant hbFGF was confirmed by using L929 and BALB/c3T3 fibroblasts. Overall, this method has the potential for large scale production of recombinant hbFGF.

An aptamer-based four-color fluorometic method for simultaneous determination and imaging of alpha-fetoprotein, vascular endothelial growth factor-165, carcinoembryonic antigen and human epidermal growth factor receptor 2 in living cells.

The extraordinary fluorescence quenching capability of graphene oxide (GO) was coupled to the specific recognition capability of aptamers to design a four-color fluorescent nanoprobe for multiplexed detection and imaging of tumor-associated proteins in living cells. Specifically, alpha-fetoprotein (AFP), vascular endothelial growth factor-165 (VEGF165), carcinoembryonic antigen (CEA), and human epidermal growth factor receptor 2 (HER2) were detected. Due to strong π interaction, the fluorescence of labeled aptamers is quenched by GO. Four fluorophore-labeled aptamers that bind the tumor-associated proteins were adsorbed on GO to form the four-color nanoprobe with quenched fluorescence. The nanoprobes were internalized into cells via endocytosis, where the aptamer/GO nanoprobes bind the intracellular tumor-associated proteins. The aptamer-protein complexes thus formed detach from GO, and fluorescence recovers. Each analyte has its typical color (AFP: blue; VEGF165: green; CEA: yellow; HER2: red). As a result, simultaneous detection and imaging of multiple tumor-associated proteins in living cells were achieved. This nanoprobe has a fast response and is highly specific and biocompatible. The linear ranges for AFP, VEGF165, CEA, and HER2 are 0.8 nM-160 nM, 0.5 nM-100 nM, 1.0 nM-200 nM, and 1.2 nM-240 nM, respectively. Detection limits were 0.45 nM for AFP, 0.30 nM for VEGF165, 0.62 nM for CEA, and 0.96 nM for HER2. The probe allows for a fast distinction between tumor cells and normal cells via imaging. Graphical abstract Schematic presentation of the development of a four-color fluorometic method based on aptamer and graphene oxide for simultaneous detection and imaging of alpha-fetoprotein, vascular endothelial growth factor-165, carcinoembryonic antigen and human epidermal growth factor receptor 2 in living cells.

Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice.

Timosaponin B-II (TB-II) is a main active saponin isolated from the rhizome of Anemarrhena asphodeloides Bge., which is widely used in traditional Chinese medicine. In this study, the effect of TB-II on learning and memory was investigated in a scopolamine-induced mouse model of Alzheimer's disease. The results of behavioral tests indicated that TB-II significantly increased the spontaneous alternation in the Y-maze test, and reversed the shortening of step-through latency induced by scopolamine in the passive avoidance test, showing protective effects on short-term and working memory. In the Morris water maze test, TB-II reduced the escape latency time in the training trial, and increased the swimming time in the target quadrant in the probe trial. Biochemical data demonstrated that TB-II significantly inhibited acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus of mice. Moreover, TB-II markably attenuated the reduction in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and decreased malondialdehyde (MDA) levels, which are key biomarkers of brain oxidative stress. These results indicated that TB-II offers protection against scopolamine-induced deficits in learning and memory, possibly by inhibiting AChE and preventing oxidative stress damage. The findings suggested that TB-II has a potential therapeutic effect on cognitive and behavioral impairment.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Genome-wide analysis of transcription factors in hippocampal tissue of cerebral palsy rats after acupuncture treatment.

BACKGROUND: Acupuncture has been shown to be effective in treating cerebral palsy (CP), reducing muscle tension, and improving motor function. However, macro-screening of key gene sets and gene-causal interaction networks for their therapeutic mechanisms have not been studied. METHODS: Applying high-throughput sequencing technology, this research discussed differentially expressed mRNAs and differential alternative splicing pre-mRNAs at the transcriptome level in rats with CP treated with acupuncture and moxibustion, and analyzed the regulatory mechanisms of these differentially expressed genes (DEGs) in CP. Changes in the levels of transcripts and alternative splicing in the hippocampi of CP rats after acupuncture treatment were analyzed. Global genes that were differentially expressed and alternative splicing events (ASEs) and regulated ASEs (RASEs) in acupuncture treatment of CP rats were analyzed. RESULTS: The RNA-seq data of acupuncture-treated rat hippocampi revealed 198 DEGs, 125 of which were related to CP, and the transcriptional regulation of RNA polymerase II was up-regulated; moreover, there were 1168 significantly different ASEs associated with CP and transcriptional regulation. There were 14 overlapping gene expression changes in transcription factors (TFs) and DEGs. CONCLUSIONS: This study found that 14 TFs were differentially expressed and a large number of TFs underwent differential alternative splicing. It is speculated that these TFs and the translated proteins of the two different transcripts produced by the differential alternative splicing of these TFs may play corresponding functions in acupuncture treatment of young rats with CP by modulating the differential expression of their target mRNAs.