OBJECTIVE To evaluate the efficacy， safety and economics of the centrally procured generic versus original esomeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding （ANVUGIB）. METHODS A retrospective collection of real-world clinical data was conducted for ANVUGIB patients who received treatment at Shenzhen People’s Hospital and University of Hong Kong-Shenzhen Hospital from January 2018 to March 2024. Patients were divided into imported original drug group （original drug group， 221 cases） and centrally procured generic drug group （generic drug group， 75 cases） according to the types of drug used. Propensity score matching （PSM） was performed at a ratio of 3∶1 to compare the clinical efficacy， safety and economics between the two groups. RESULTS Totally 241 patients were included after PSM， with 170 in the original drug group and 71 in the generic drug group. There were no significant differences between the two groups in terms of rebleeding rate， rate of second endoscopic intervention， blood transfusion rate， length of hospital stay， mortality due to gastrointestinal bleeding， 30-day readmission due to rebleeding， and overall survival rate （P＞0.05）. The incidence of adverse events among all patients in both groups also showed no statistically significant difference （P＞0.05）； furthermore， the adverse events reported by the respective hospitals to the National Center for ADR Monitoring were comparable between the two groups. After PSM， the median total drug cost and high-dose esomeprazole cost in the generic drug group were significantly lower than those in the original drug group， while the median nursing fee and bed fee were significantly higher than those in the original drug group （P＜0.05）. There was no statistically significant difference between the two groups in terms of median total hospitalization expenses， total treatment costs， laboratory fees， examination fees， material costs， or consultation fees （P＞0.05）. CONCLUSIONS The clinical efficacy and safety of centrally procured generic esomeprazole in the treatment of ANVUGIB are comparable to those of the original drug， and it is more economical.

In recent years, with the continuous development of in situ cryo-electron microscopy (cryo-EM) and artificial intelligence (AI) technologies, the research of structural biology has undergone a paradigm shift. Structural analysis is no longer confined to isolated and purified biomolecules, and determination of high-resolution in situ structures directly within cells and tissues becomes feasible. Furthermore, structural analysis of the molecular landscapes of subcellular regions can be performed to gain a deeper understanding of the molecular mechanisms of living activities in the native functional context. Through determining in situ structures of various protein complexes within the cell, it is feasible to visualize the proteome with spatial and quantitative information, which is often referred to as visual proteomics. Emerging in situ structural methods represented by cryo-electron tomography (cryo-ET) hold the promise to elucidate the three-dimensional interaction networks of the intracellular proteome and understand their activities in a systematic manner. To advance in situ cryo-EM/ET and visual proteomics in China, this review summarizes the new research paradigms and technological advances, showcases the superiority of new concepts and technologies with representative examples, and discusses the future prospects in the field.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Mice ; Animals ; Humans ; Glioblastoma/pathology* ; Endothelial Cells/pathology* ; DNA Copy Number Variations ; Brain/metabolism* ; Brain Neoplasms/pathology*

Introduction: Advanced glycation end product (AGE) is formed by the non-enzymatic glycation, leading to free radicals’ production and high oxidative stress. Accumulation of AGEs is associated with chronic diseases which are correlated with diabetes mellitus. Centella asiatica is a traditional medicinal herb used in Asia with numerous pharmacological effects such as antioxidant, wound healing, neuroprotective, and gastrointestinal treatment. This research was aim to evaluate the antioxidant, antiglycation, and phytochemical analysis of C. asiatica leaves (L.) water extract. Methods: The antioxidant activity of the plant extract was evaluated through 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH) radicals, nitric oxide (NO), and chelating capacity assays. Total phenolic content (TPC) was performed to determine the presence of bioactive compounds, such as saponins, which have been extensively reported in previous studies. Butylated hydroxytoluene (BHT) and ethylenediaminetetraacetic acid (EDTA) were used as positive control in the antioxidant assays, while quercetin was used in the antiglycation assays. Antiglycation effects of C. asiatica L. were evaluated through Bovine serum albumin (BSA)-MGO, BSA-glucose, and MGO scavenging assay. The data was expressed in terms of IC50. Result: The plant extract possessed significantly (p < 0.001) lower IC50 value compared to the BHT in DPPH and NO radical scavenging assay. It also showed stronger antiglycative effect with lower IC50 value compared to the quercetin in BSA-glucose and BSA-MGO assay. The TPC of C. asiatica L. was 3.20 mg/GAE/g at 100µg/ml. Conclusion: The antiglycation effects of C. asiaitca L. include the reduction of Amadori products formation, trapping α-dicarbonyl intermediates, and free radical scavenging. It is suggested that the antiglycation effects of C. asiatica L. maybe attributed by the presence of saponins and other phytochemicals.

Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.

INTRODUCTION: Flexible bronchoscopic intubation (FBI) is an important technique in managing an anticipated difficult airway, yet it is rarely performed and has a steep learning curve. We aim to evaluate if the integration of virtual reality gaming application into routine FBI training for emergency department doctors would be more effective than traditional teaching methods. METHODS: We conducted a randomised controlled trial to compare self-directed learning using the mobile application, Airway Ex* in the intervention group versus the control group without use of the mobile application. All participants underwent conventional didactic teaching and low-fidelity simulation with trainer's demonstration and hands-on practice on a manikin for FBI. Participants randomised to the intervention arm received an additional 30 minutes of self-directed learning using Airway Ex, preloaded on electronic devices while the control arm did not. The primary outcome was time taken to successful intubation. RESULTS: Forty-five physicians (20 junior and 25 senior physicians) were enrolled, with male predominance (57.8%, 26/45). There was no difference in time taken to successful intubation (median 48 seconds [interquartile range, IQR 41-69] versus 44 seconds [IQR 37-60], P=0.23) between the control and intervention groups, respectively. However, the intervention group received better ratings (median 4 [IQR 4-5]) for the quality of scope manipulation skills compared to control (median 4 [IQR 3-4], adjusted P=0.03). This difference remains significant among junior physicians in stratified analysis. CONCLUSION Incorporating virtual reality with traditional teaching methods allows learners to be trained on FBI safely without compromising patient care. Junior physicians appear to benefit more compared to senior physicians.

The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1∶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.
Animals ; Apiaceae ; Aquaporin 4 ; Colitis, Ulcerative ; Colon ; Intestinal Mucosa ; Male ; Mice ; Plant Roots ; Rats

Adaptation, Psychological ; Adult ; Age Factors ; Aged ; Beijing/epidemiology* ; Breast Neoplasms/psychology* ; Case-Control Studies ; Educational Status ; Female ; Humans ; Middle Aged ; Risk Factors

Adolescent ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Leukemia ; drug therapy ; mortality ; therapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; therapy ; Male ; Mycophenolic Acid ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Retrospective Studies ; Treatment Outcome