[摘 要] 目的：探讨绿茶单体表没食子儿茶素没食子酸酯（EGCG）对大鼠肝癌发生过程中肠道菌群结构变化的影响。方法：建立二乙基亚硝胺（DEN）诱导的肝癌大鼠模型。将26只SD大鼠随机分成3组，分别为正常对照组、肝癌组和EGCG干预组。从实验开始第1天起，EGCG干预组每日给予EGCG（40 mg/kg）灌胃，正常对照组和肝癌组给予等量生理盐水灌胃，1次/日，持续至第20周。灌胃结束后，采集大鼠粪便样本，提取DNA，进行高通量16S rRNA V3-V4区测序；处死大鼠，取肝，观察肿瘤形成情况，并计算肝癌发生率。对测序数据进行生物信息学分析：经质控、聚类获得操作分类单元（OTU）表，据此计算α多样性指数（包括Observed species、Chao1、Shannon和Simpson指数），并进行β多样性分析。同时，对物种进行分类学注释，比较各组间菌群组成与丰度差异。结果： EGCG干预组大鼠（8只）肝脏肿瘤形成率明显低于肝癌组（10只）（50% vs 100%， P = 0.023），正常对照组（8只）大鼠无肿瘤发生。在肠道菌群方面，肝癌组操作分类单元（OTU）数量远低于正常对照组（P <0.001），而EGCG干预组OTU数量总体上高于肝癌组（P = 0.021）。α多样性分析显示，肝癌组Shannon指数低于正常对照组（P < 0.05）；此外，与肝癌组相比，EGCG干预组的Observed species指数、Chao1指数、Shannon指数和Simpson指数均显著提高（P < 0.05）。β多样性分析及主坐标分析（PCoA）表明，三组肠道菌群结构存在显著分离（PERMANOVA， R² = 0.3918， P = 0.001），其中EGCG干预组群落结构介于肝癌组与正常对照组之间，并更接近于正常对照组。肝癌组大鼠较正常大鼠肠道菌群中链球菌等潜在致病菌富集，丁酸产生相关菌（如丁酸球菌属、瘤胃球菌属等）丰度显著降低（P < 0.05）。相比之下，在EGCG干预肝癌发生过程中，大鼠肠道菌群结构相对稳定。厚壁菌门/拟杆菌门比值较肝癌组显著提高（P < 0.05），益生菌（如双歧杆菌属、乳杆菌属等）和丁酸产生相关菌（如丁酸球菌属）富集。结论：EGCG干预可降低DEN诱导的大鼠肝癌发生率，并有助于稳定肠道菌群结构，其作用可能与增加菌群多样性、促进益生菌及丁酸产生菌富集、恢复菌群平衡有关。

Objective:To investigate the outcomes of endoscopic balloon dilation laryngoplasty （EBDL） in managing acquired subglottic stenosis in children. Methods:A retrospective analysis of clinical data from patients who underwent endoscopic balloon dilation for secondary subglottic stenosis between January 2017 and January 2024 at Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai. The study included 10 children （6 males, 4 females） aged between 13 days and 3 years at the time of their first procedure, with an average age of 7 months. Subglottic stenosis was graded according to the Myer-Cotton classification, with two cases classified as grade Ⅱ and eight cases as grade Ⅲ. All patients had a history of tracheal intubation, including seven for rescue purposes and three for operations. Eight cases were complicated by other conditions: two with atrial septal defect, patent ductus arteriosus, and patent foramen ovale; two with patent foramen ovale only; one with atrial septal defect and extreme deafness in the left ear; one with a brain tumor and hydrocephalus; one with a traumatic diaphragmatic hernia and hepatic rupture; and one case complicated by type Ⅰ laryngeal cleft. Prior to surgery, all children required respiratory support-seven needed high-flow oxygen while three required CPAP. Results:All ten cases underwent endoscopic balloon dilation under spontaneous respiration and general anesthesia, totaling fourteen dilations （an average of 1.4 dilations per person） without any complications. Post-surgery air permeability tests showed that eight cases had grade Ⅰ stenosis while two had grade Ⅱ stenosis. The follow-up period ranged from six months to six years （average duration: 46 months）. Following treatment, all patients no longer required respiratory support or experienced significant mobility limitations. Conclusion:Endoscopic balloon dilation under general anesthesia is deemed safe and effective in treating secondary subglottic stenosis. Early diagnosis coupled with prompt intervention can help avoid tracheotomy procedures altogether. Standard tracheoscopy combined with breathability testing represents a crucial approach to assess normal airway diameter and effectively reduce or prevent secondary subglottic stenosis following re-intubation.
Humans ; Laryngostenosis/surgery* ; Male ; Female ; Retrospective Studies ; Laryngoplasty/methods* ; Child, Preschool ; Infant ; Dilatation/methods* ; Laryngoscopy/methods* ; Treatment Outcome ; Endoscopy

Background and purpose:In recent years,deep inspiration breath hold(DIBH)based on surface-guided radiation therapy(SGRT)has emerged as one of the most promising techniques in breast cancer radiotherapy.Conventionally,cone-beam CT(CBCT)is used before treatment to verify and correct patient positioning deviations.However,patient position may change during treatment,and pre-fraction CBCT cannot fully reflect real-time positional deviations.Therefore,this study aimed to introduce intra-fraction CBCT into left-sided breast DIBH radiotherapy to monitor and correct real-time deviations,verify whether patients achieve the desired position during treatment,and evaluate the clinical value of intra-fraction CBCT in left-breast radiotherapy.Methods:Clinical data from postoperative left-sided breast cancer patients treated at Fudan University Shanghai Cancer Center between June 2023 and January 2024 were collected.Patients with satisfactory cardiopulmonary function and stable DIBH compliance were included.Pre-fraction CBCT scans were performed before treatment,and data were recorded.During treatment,the gantry was rotated to-180° to trigger kV-level intra-fraction CBCT scanning.After gantry repositioning to the starting angle of the tangential field,MV beam delivery commenced.Intra-fraction CBCT scans were acquired for positional registration,and deviations were compared with pre-fraction CBCT results.Results:A total of 30 eligible patients were included,with 150 pairs of pre-fraction and intra-fraction CBCT images analyzed per patient.The mean registration deviations for intra-fraction CBCT were 26%,52%,and 51%lower than pre-fraction CBCT in the X,Y,and Z axes,respectively(P＜0.05),demonstrating significantly reduced real-time deviations.The probability of intra-fraction deviations being＜6 mm was 100.0%,100.0%,and 99.3%for the X,Y,and Z axes,respectively.Correlation analysis revealed a weak correlation between intra-fraction and pre-fraction deviations in the X-axis(P＜0.05),while no significant correlation was observed for the Y and Z axes(P＞0.05).Conclusion:Intra-fraction CBCT effectively monitors and corrects real-time positional deviations in left-sided breast DIBH radiotherapy,serving as a valuable supplement to conventional pre-fraction CBCT.It minimally impacts treatment efficiency while significantly improving positional accuracy,offering clinical and practical benefits for left-breast cancer radiotherapy.

BACKGROUND:The long-term effect of All-on-4 implant fixed denture is closely related to biomechanics.Its occlusion design affects the stress distribution of every part of the restoration.However,there is limited and inconclusive biomechanical research on All-on-4 implant fixed denture both domestically and internationally so far.OBJECTIVE:To analyze the effect of different occlusal contacts on the stress distribution of mandibular All-on-4 implant fixed denture.METHODS:A model of mandibular All-on-4 implant fixed denture was established.By changing the loading force,direction,and position,10 loading conditions were set up to simulate centric occlusion,laterotrusive occlusion,and protrusive occlusion.The stress distribution and maximum stress values of every part of the model in different loading conditions were analyzed and compared among each group of models by loading different tooth positions to simulate different occlusal contact types.RESULTS AND CONCLUSION:(1)The stress distribution cloud diagrams of each group of models were basically similar.The stress of the implant was mainly concentrated at the implant neck.The stress of the surrounding bone tissue was mainly concentrated around the implant neck,and the stress of the cortical bone was significantly higher than that of the cancellous bone.The stress of the abutment was mainly concentrated at the connection between the abutment and the implant and the abutment and the upper restoration.The stress of the titanium bracket in the upper restoration was mainly concentrated at the connection between the abutment and the titanium bracket,and the stress of the resin surface in the upper restoration was mainly concentrated on each loading point.(2)In simulating centric occlusion,the maximum stress value of the implant significantly increased when the cantilever was not loaded.It indicates that the mandibular All-on-4 implant fixed denture can have occlusal contact in the distal cantilever during centric occlusion.(3)In simulating laterotrusive occlusion,the maximum stress values of every part of the model significantly increased when simulating canine-guided occlusion.The maximum stress value of the simulated laterotrusive balanced occlusion was slightly lower than that of the simulated group functional occlusion.It indicates that group functional occlusion can be selected in the permanent prosthesis after osseointegration and laterotrusive balanced occlusion can be selected in the provisional restoration of mandibular All-on-4 implant fixed denture.(4)In simulating protrusive occlusion,the maximum stress values of every part of the model significantly increase when only the front tooth is loaded.In simulating protrusive balanced occlusion,the maximum Von-Mises stress value is relatively small.It indicates that the protrusive occlusion of mandibular All-on-4 implant fixed denture can choose protrusive balanced occlusion.

Objective To identify the core constitutions and prodromal symptoms of relapse in schizophrenia patients using network analysis,and to analyze their relationships as well as gender differences.Methods Schizophrenia patients hospitalized in the psychiatry department of Hunan Brain Hospital in Hunan Province between October 2022 and December 2023 were selected as survey participants.A general information questionnaire,a Traditional Chinese Medicine Constitution Scale,and a Schizophrenia Prodromal Symptoms of Relapse Scale were used for investigation.Network anal-ysis was conducted using R language.Results The core constitutions of schizophrenia patients were qi deficiency constitution[Expected Influence(EI)=1.08]and dampness-heat constitution(EI=1.00),and the core prodromal symptoms of relapse were depression/withdrawal(EI=0.84)and ini-tial psychotic manifestations(EI=0.81).There were statistically significant differences in constitutions of traditional Chinese medicine and prodromal symptoms of relapse between patients of different genders(P＜0.05).Females mainly exhibited qi deficiency constitution(EI=1.20)with anxiety as the core prodromal symptom(EI=0.98),while males mainly exhibited yin deficiency constitution(EI=1.05)with depression/withdrawal as the core prodromal symptom(EI=1.00).Conclusion Healthcare professionals can early identify core prodromal symptoms of relapse by core imbalanced constitutions of schizophrenia patients,and develop precise intervention strategies,thereby promoting changes in their network structure,preventing disease relapse,and improving patients'quality of life.

Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.

BACKGROUND:The long-term effect of All-on-4 implant fixed denture is closely related to biomechanics.Its occlusion design affects the stress distribution of every part of the restoration.However,there is limited and inconclusive biomechanical research on All-on-4 implant fixed denture both domestically and internationally so far.OBJECTIVE:To analyze the effect of different occlusal contacts on the stress distribution of mandibular All-on-4 implant fixed denture.METHODS:A model of mandibular All-on-4 implant fixed denture was established.By changing the loading force,direction,and position,10 loading conditions were set up to simulate centric occlusion,laterotrusive occlusion,and protrusive occlusion.The stress distribution and maximum stress values of every part of the model in different loading conditions were analyzed and compared among each group of models by loading different tooth positions to simulate different occlusal contact types.RESULTS AND CONCLUSION:(1)The stress distribution cloud diagrams of each group of models were basically similar.The stress of the implant was mainly concentrated at the implant neck.The stress of the surrounding bone tissue was mainly concentrated around the implant neck,and the stress of the cortical bone was significantly higher than that of the cancellous bone.The stress of the abutment was mainly concentrated at the connection between the abutment and the implant and the abutment and the upper restoration.The stress of the titanium bracket in the upper restoration was mainly concentrated at the connection between the abutment and the titanium bracket,and the stress of the resin surface in the upper restoration was mainly concentrated on each loading point.(2)In simulating centric occlusion,the maximum stress value of the implant significantly increased when the cantilever was not loaded.It indicates that the mandibular All-on-4 implant fixed denture can have occlusal contact in the distal cantilever during centric occlusion.(3)In simulating laterotrusive occlusion,the maximum stress values of every part of the model significantly increased when simulating canine-guided occlusion.The maximum stress value of the simulated laterotrusive balanced occlusion was slightly lower than that of the simulated group functional occlusion.It indicates that group functional occlusion can be selected in the permanent prosthesis after osseointegration and laterotrusive balanced occlusion can be selected in the provisional restoration of mandibular All-on-4 implant fixed denture.(4)In simulating protrusive occlusion,the maximum stress values of every part of the model significantly increase when only the front tooth is loaded.In simulating protrusive balanced occlusion,the maximum Von-Mises stress value is relatively small.It indicates that the protrusive occlusion of mandibular All-on-4 implant fixed denture can choose protrusive balanced occlusion.

Background and purpose:In recent years,deep inspiration breath hold(DIBH)based on surface-guided radiation therapy(SGRT)has emerged as one of the most promising techniques in breast cancer radiotherapy.Conventionally,cone-beam CT(CBCT)is used before treatment to verify and correct patient positioning deviations.However,patient position may change during treatment,and pre-fraction CBCT cannot fully reflect real-time positional deviations.Therefore,this study aimed to introduce intra-fraction CBCT into left-sided breast DIBH radiotherapy to monitor and correct real-time deviations,verify whether patients achieve the desired position during treatment,and evaluate the clinical value of intra-fraction CBCT in left-breast radiotherapy.Methods:Clinical data from postoperative left-sided breast cancer patients treated at Fudan University Shanghai Cancer Center between June 2023 and January 2024 were collected.Patients with satisfactory cardiopulmonary function and stable DIBH compliance were included.Pre-fraction CBCT scans were performed before treatment,and data were recorded.During treatment,the gantry was rotated to-180° to trigger kV-level intra-fraction CBCT scanning.After gantry repositioning to the starting angle of the tangential field,MV beam delivery commenced.Intra-fraction CBCT scans were acquired for positional registration,and deviations were compared with pre-fraction CBCT results.Results:A total of 30 eligible patients were included,with 150 pairs of pre-fraction and intra-fraction CBCT images analyzed per patient.The mean registration deviations for intra-fraction CBCT were 26%,52%,and 51%lower than pre-fraction CBCT in the X,Y,and Z axes,respectively(P＜0.05),demonstrating significantly reduced real-time deviations.The probability of intra-fraction deviations being＜6 mm was 100.0%,100.0%,and 99.3%for the X,Y,and Z axes,respectively.Correlation analysis revealed a weak correlation between intra-fraction and pre-fraction deviations in the X-axis(P＜0.05),while no significant correlation was observed for the Y and Z axes(P＞0.05).Conclusion:Intra-fraction CBCT effectively monitors and corrects real-time positional deviations in left-sided breast DIBH radiotherapy,serving as a valuable supplement to conventional pre-fraction CBCT.It minimally impacts treatment efficiency while significantly improving positional accuracy,offering clinical and practical benefits for left-breast cancer radiotherapy.

Objective To explore the effects of Dushu pills on cognitive ability and mitochondrial dynamics related proteins in mouse model of Alzheimer's disease(AD)based on network pharmacology.Methods The corresponding targets of Dushu pills and its related targets with AD were predicted using TCMSP database.The intersection targets of Dushu pills and AD were obtained by Venny website.The protein interaction network and drug-disease-target network were mapped using String database and Cytoscape software,respectively.GO and KEGG enrichment analysis were performed for intersection targets using David database.The mouse model of AD was established by injecting Aβ25-35 into bilateral ventricles.The learning and memory ability of the mice was detected by behavioral tests,the mitochondrial damage of neurons in the hippocampus was observed by transmission electron microscopy,and the expression of proteins related to mitochondrial dynamics was detected by Western blot.Results A total of 311 intersection targets related to drugs and diseases were screened out from the database.GO and KEGG analysis showed that the relevant targets were concentrated in mitochondria and other components,and concentrated in the pathways of ATP binding and positive regulation of MAPK activity.Compared with the normal group,the learning and memory ability of the model group was decreased(P<0.05),mitochondrial ridges appeared swelling and fracture(P<0.0001),decreased expression of MAPK,Mfn2 and OPA1 proteins in hippocampus(P<0.01),the expression of DRP1 protein increased(P<0.01).Compared with the model group,the learning and memory ability of mice in the medium and high dose groups of Dushu pills was improved(P<0.05),mitochondrial damage was significantly improved(P<0.01),increased expression of MAPK,Mfn2 and OPA1 in the hippocampus(P<0.01),DRP1 protein expression decreased(P<0.01).Conclusion Dushu pills can reduce mitochondrial damage,maintain mitochondrial homeostasis,and improve the cognitive and memory ability of AD mice.