Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective To investigate the effects of folate deficiency on changes in histone H3 lysine 4 (H3K4) mono-methylation (me1)-marked enhancers and the molecular mechanism underpinning the folate deficiency-induced neural tube defects (NTD). Methods Mouse embryonic stem cells (mESCs) were cultured in the folate-free DMEM medium (folate-deficient group) and the DMEM medium containing 4 mg/L folate (normal control group),respectively.Chromatin immunoprecipitation sequencing (ChIP-seq) was performed for H3K4me1. The mouse model of folate-induced NTD was established,and transcriptome sequencing (RNA-seq) was performed for the brain tissue of fetal mice to reveal the differential expression profiles.The results were validated through real-time quantitative polymerase chain reaction (RT-qPCR).The activity of the differential peak regions of H3K4me1 was verified through the luciferase reporter assay. Results The folate content in the mESCs cultured in the folate-free medium reduced compared with that in the normal control group (P=0.008).The H3K4me1-maked enhancers in the mESCs cultured in the folate-free medium induced significant changes in intronic regions,and these changes were concentrated in metabolic and energy metabolism processes (q=9.56×10^-48,P=1.28×10^-47).The differentially expressed genes harboring H3K4me1-marked enhancers in mESCs were mainly enriched in the Wnt signaling pathway (q=0.004,P=0.004 7).ChIP-qPCR results confirmed that H3K4me1 binding decreased in the differential peak regions of the Ldlrap1 gene (P=0.008),Camta1 gene (P=0.002),and Apc2 gene (P=0.012).The H3K4 demethylase inhibitor T-448 effectively reversed the H3K4me1 binding in the differential peak regions of the aforementioned genes (P=0.01).The results of RNA-seq for the brain tissue of NTD fetal mice showed significant enrichment of the differentially expressed genes in the Wnt signaling pathway (P=1.52×10^-5).The enrichment of differential peak regions of H3K4me1-marked enhancers in Apc2,Ldlrap1,and Camta1 genes in the brain tissue also showed significant changes.The differential peak region in Apc2 exhibited transcription factor activity (P=0.020). Conclusion Folate deficiency may affect changes in H3K4me1-marked enhancers to participate in the regulation of neural tube closure genes,thereby inducing the occurrence of NTD.
Neural Tube Defects/genetics* ; Animals ; Mice ; Folic Acid Deficiency/complications* ; Histones/metabolism* ; Folic Acid/metabolism* ; Methylation ; Mouse Embryonic Stem Cells/metabolism* ; Wnt Signaling Pathway ; Lysine/metabolism* ; Chromatin Immunoprecipitation Sequencing

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective:To evaluate the performance of an artificial intelligence-based endoscopic virtual ruler (EVR) for non-invasive measurement of esophageal varices (EV) diameter.Methods:Patients with liver cirrhosis and EV hospitalized at the First Affiliated Hospital of Anhui Medical University between October 2022 and May 2023 were prospectively enrolled. EV diameter was measured using visual estimation, esophageal varix manometer (EVM), and EVR, with procedure times recorded. The intraclass correlation coefficient (ICC) was used to assess the consistency of EV diameter measurement obtained from the three methods, and repeated-measures ANOVA was used to compare differences in time measurements across three methods.Results:The study included 41 patients with liver cirrhosis and EV. Inter-observer ICC for visual estimation was 0.594, versus 0.840 for EVM and 0.884 for EVR. The ICC value between the EV diameters measured by EVR and EVM was higher than that of the visual assessment. The ICC value between EV diameter measurement by EVM and EVR was 0.991. Measurement times differed significantly across methods ( P<0.001): visual estimation 18.6±2.2 s (14.7-23.3 s), EVR 41.5±4.1 s (31.7-50.3 s), and EVM 170.8±26.4 s (129.3-229.3 s). Repeated measures analysis of variance (corrected using Greenhouse-Geisser) revealed significant differences in time across the three measurement methods [ F(1.033, 41.313)=1 233.800, P<0.001]. Subsequent Bonferroni post-hoc tests revealed significant differences in time between all method pairs ( P<0.001). Conclusion:EVR provides rapid, non-invasive EV diameter measurements with excellent agreement to EVM assessment, offering an efficient alternative to conventional techniques.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective:To explore whether a history of cardiovascular disease (CVD) history in the middle-aged and elderly populations in China is an independent risk factor for Parkinson's disease (PD).Methods:Based on China Health and Retirement Longitudinal Study (CHARLS) database, middle-aged and elderly populations aged 45 years and above in China who did not have PD in 2011 were chosen; their demographic characteristics, health status and lifestyle were collected. These individuals were divided into a PD group and a non-PD group based on whether they had been diagnosed as having PD during follow-up survey in 2020. Multivariate Logistic regression was performed to analyze the association between CVD history and PD. Stratified analysis was conducted based on age (whether ≥60 years old), gender, educational attainment, and presences of chronic lung disease history, diabetes and high blood sugar history, and interaction effects of the above factors with CVD history were analyzed to examine the robustness in different populations. PROCESS software was applied to construct a single mediator chain reaction model; with average daily sleep duration and depression score (based on Depression Scale from Center for Epidemiologic Studies) one month before survey as mediator variables, mediating effect was analyzed.Results:A total of 10,465 individuals were ultimately included, including 101 with PD and 10,364 without PD. CVD history ( OR=2.882, 95% CI: 1.610-5.159, P<0.001) was an independent risk factor for PD. For individuals with different gender, with presence of chronic lung diseases history, aged over 60 years, and with educational level of elementary school and above, and without diabetes or high blood sugar history, CVD history was significantly associated with PD onset ( P<0.05). Significant interations weren't revealed between the above factors with CVD history. The average daily sleep duration ( β=1.114, 95% CI: 0.687-1.540) and depression score ( β=1.060, 95% CI: 0.627-1.493) showed partial mediation effects between the two diseases (95% CI for direct effect parameters not including 0). Conclusion:Chinese middle-aged and elderly populations with CVD history are prone to have PD, with average daily sleep duration and depression score serving as potential mediating factors.

Clinical pharmacist training is an important way to strengthen the clinical pharmacist team's construction and improve their pharmaceutical service capabilities and levels.The Pharmacy Administration and Pharmacy Practice in Healthcare Institutions-Part 4-8-1:Pharmacy Administration-Pharmacy Training Management-Clinical Pharmacist Training was based on the relevant requirements of the current clinical pharmacist training system of the Chinese Hospital Association,and formulated by sor-ting out relevant materials,such as standards,policies and regulations,technical specifications,literature,the current situation of clinical pharmacist training in China,and expert opinions.A total of 15 key elements of clinical pharmacist training were selected and divided into three aspects(base management,training process and assessment,and the quality management,evaluation and improvement).This article mainly introduced the construction method and content of the clinical pharmacist training standard,to deepen the understanding of the standard for relevant units and to promote the implementation of the standard.

Objective:To investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.