Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses ...Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses the law of large numbers and the central limit theorem to model to carry out the case study of FAHSYSU Simulation T,and takes measures of offsetting adverse selections to increase booking efficiency.The paper also analyzes how to apply the ancient Chinese theory that man is an integral part of nature to wipe out‘the market for lemons’.展开更多
To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic p...To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic pancreatitis and pancreatic carcinoma,especially acinar cell carcinoma[1,2].The clinical manifestations are nonspecific erythema tender nodules.展开更多
BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium.Timely medical contact is critical for succes...BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium.Timely medical contact is critical for successful AMI treatment,and delays increase the risk of death for patients.Pre-hospital delay time(PDT)is a significant challenge for reducing treatment times,as identifying high-risk patients with AMI remains difficult.This study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care,ultimately reducing PDT and improving treatment outcomes.AIM To construct a nomogram model for forecasting pre-hospital delay(PHD)likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD risk.METHODS A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September 2022.The study included 252 patients,with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 ratio.Independent risk factors influencing PHD were identified in the development group,leading to the establishment of a nomogram model for predicting PHD in patients with AMI.The model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation groups.RESULTS Independent risk factors for PHD in patients with AMI included living alone,hyperlipidemia,age,diabetes mellitus,and digestive system diseases(P<0.05).A characteristic curve analysis indicated area under the receiver operating characteristic curve values of 0.787(95%confidence interval:0.716–0.858)and 0.770(95%confidence interval:0.660-0.879)in the development and validation groups,respectively,demonstrating the model's good discriminatory ability.The Hosmer–Lemeshow goodness-of-fit test revealed no statistically significant disparity between the anticipated and observed incidence of PHD in both development and validation cohorts(P>0.05),indicating satisfactory model calibration.CONCLUSION The nomogram model,developed with independent risk factors,accurately forecasts PHD likelihood in AMI individuals,enabling efficient identification of PHD risk in these patients.展开更多
Objective: To evaluate the role of prevention and control strategies for nosocomial infection in a tertiary teaching hospital during the sudden outbreak of Corona Virus Disease 2019 (COVID-19). Methods: The hospital i...Objective: To evaluate the role of prevention and control strategies for nosocomial infection in a tertiary teaching hospital during the sudden outbreak of Corona Virus Disease 2019 (COVID-19). Methods: The hospital initiated an emergency plan involving multi-departmental defense and control. It adopted a series of nosocomial infection prevention and control measures, including strengthening pre-examination and triage, optimizing the consultation process, improving the hospital’s architectural composition, implementing graded risk management, enhancing personal protection, and implementing staff training and supervision. Descriptive research was used to evaluate the short-term effects of these in-hospital prevention and control strategies. The analysis compared changes in related evaluation indicators between January 24, 2020 and February 12, 2020 (Chinese Lunar New Year’s Eve 2020 to lunar January 19) and the corresponding lunar period of the previous year. Results: Compared to the same period last year, the outpatient fever rate increased by 1.85-fold (P P Conclusion: The nosocomial infection prevention and control strategies implemented during this specific period improved the detection and control abilities for the COVID-19 source of infection and enhanced the compliance with measures. This likely contributed significantly to avoiding the occurrence of nosocomial infection.展开更多
Objective:To build a set of teaching staff construction and teaching quality monitoring system suitable for clinical practice teaching in affiliated hospitals of medical colleges,achieve continuous improvement of clin...Objective:To build a set of teaching staff construction and teaching quality monitoring system suitable for clinical practice teaching in affiliated hospitals of medical colleges,achieve continuous improvement of clinical education and teaching level,and ensure the quality of medical education talent cultivation.Methods:A modern clinical practice teaching quality monitoring system is constructed based on organizational structure construction,teaching staff system construction,quality control system construction,and information platform construction,combined with external audit and evaluation.Results:The hospital has established a Faculty Development and Teaching Evaluation Office specifically responsible for the cultivation of clinical teachers and the evaluation and supervision of teaching quality.A relatively complete teacher construction and teaching quality monitoring system has also been established for clinical practice teaching,thus achieving integration with the school’s quality control system in terms of management mechanism.At the same time,a set of teaching quality control mode based on the“Internet+”platform has been created by means of informatization.At present,this mode has won three national computer software copyrights and two second prizes for school-level teaching achievements.Conclusion:Through five years of practice,an“Internet+”teaching quality evaluation and monitoring system with the characteristics of teaching hospitals affiliated to local medical colleges has been established.In order to further standardize the training system of clinical teachers in affiliated hospitals,achieve self-monitoring and self-improvement in terms of teaching quality,and ensure the continuous improvement of clinical teaching quality,we will continue to promote the development of clinical teachers with quality and excellence,enrich the main team of quality monitoring,guide the transformation of the education mode from being“centered on teachers”to being“centered on students,”and realize the integration of internal and external quality monitoring systems.展开更多
To further improve the ability of pre-hospital and in-hospital collaborative treatment, strengthen emergency multidisciplinary cooperation and construct a scientific, rational and efficient emergency system, under the...To further improve the ability of pre-hospital and in-hospital collaborative treatment, strengthen emergency multidisciplinary cooperation and construct a scientific, rational and efficient emergency system, under the support of former chairman Yu Xue-zhong, Dr. Li Chun-sheng and numerous colleagues in the industry, the Emergency Medicine Society of the Chinese Medical Association appeal to us to draft Construction of Emergency and Pre-hospital Platform. Based on this background, the platform of emergency and pre-hospital first aid helps to build a 'one horizontal and one Longitudinal' treatment model, using the horizontal and longitudinal patterns to integrate emergency medical resources to satisfy the automatic information integration and intelligent analysis sharing, realizing the emergency management visualization and medical information digitization, simplifying the medical process and establishing a perfect standard for the emergent diseases, thereby ultimately achieving efficient diagnosis and scientific treatment.展开更多
BACKGROUND Malignant peritoneal mesothelioma(MPeM)is a rare cancer with a poor prognosis at advanced stage,and the standard first-line treatment for inoperable patients is chemotherapy.Although combining programmed ce...BACKGROUND Malignant peritoneal mesothelioma(MPeM)is a rare cancer with a poor prognosis at advanced stage,and the standard first-line treatment for inoperable patients is chemotherapy.Although combining programmed cell death 1(PD-1)inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors,there are few reports regarding initial immunochemotherapy in advanced MPeM.CASE SUMMARY Here,to our knowledge,we present the first case of a patient with epithelioid subtype MPeM,who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival(PFS)and good tolerance.A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen.Computed tomography revealed a solid mass in the lower abdomen,which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy.The patient received eight cycles of pemetrexed 800 mg(day 1),cisplatin 60/50 mg(day 1–2),and zimberelimab(PD-1 inhibitor)240 mg(day 1)every 3 wk.He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms.The best tumor response was partial remission with a final PFS of 7 mo.No immunerelated adverse event occurred during the combination treatment.CONCLUSION The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.展开更多
Background Somatic symptom disorder(SSD)commonly presents in general hospital settings,posing challenges for healthcare professionals lacking specialised psychiatric training.The Neuro-11 Neurosis Scale(Neuro-11)offer...Background Somatic symptom disorder(SSD)commonly presents in general hospital settings,posing challenges for healthcare professionals lacking specialised psychiatric training.The Neuro-11 Neurosis Scale(Neuro-11)offers promise in screening and evaluating psychosomatic symptoms,comprising 11 concise items across three dimensions:somatic symptoms,negative emotions and adverse events.Prior research has validated the scale’s reliability,validity and theoretical framework in somatoform disorders,indicating its potential as a valuable tool for SSD screening in general hospitals.Aims This study aimed to establish the reliability,validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD.Through this comparative analysis,we aimed to validate the effectiveness and precision of the Neuro-11,enhancing its utility in clinical settings.Methods Between November 2020 and December 2021,data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People’s Hospital in China for various physical discomforts.The patients completed multiple questionnaires,including the Neuro-11,Short Form 36 Health Survey,Patient Health Questionnaire 15 items,Hamilton Anxiety Scale and Hamilton Depression Scale.Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD.Results The Neuro-11 demonstrated strong content reliability and structural consistency,correlating significantly with internationally recognised and widely used questionnaires.Despite its brevity,the Neuro-11 exhibited significant correlations with other questionnaires.A test-retest analysis yielded a correlation coefficient of 1.00,Spearman-Brown coefficient of 0.64 and Cronbach’sαcoefficient of 0.72,indicating robust content reliability and internal consistency.Confirmatory factor analysis confirmed the validity of the three-dimensional structure(p<0.001,comparative fit index=0.94,Tucker-Lewis index=0.92,root mean square error of approximation=0.06,standardised root mean square residual=0.04).The threshold of the Neuro-11 is set at 10 points based on the maximum Youden’s index from the receiver operating characteristic curve analysis.In terms of diagnostic efficacy,the Neuro-11 has an area under the curve of 0.67.展开更多
Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate trau...Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.展开更多
Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the m...Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.展开更多
The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves t...The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).展开更多
Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none o...Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.展开更多
The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients.We used propofol at a rate of 60 mg/(kg·h)in...The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients.We used propofol at a rate of 60 mg/(kg·h)in the propofol group(group P)or remimazolam at a rate of 6 mg/(kg·h)in the remimazolam group(group R)for the induction.A processed electroencephalogram was used to determine whether the induction was successful and when to stop the infusion of the study drug.We measured when patients entered the operating room(T_(0)),when the induction was successful(T_(1)),and when before(T_(2))and 5 min after successful endotracheal intubation(T_(3)).We found that mean arterial pressure(MAP)was lower at T_(1–3),compared with T_(0) in both groups,but higher at T_(2) in the group R,whileΔMAP_(T0–T2) andΔMAP_(max) were smaller in the group R(ΔMAP_(T0–T2):the difference between MAP at time point T_(0) and T_(2),ΔMAP_(max):the difference between MAP at time point T_(0) and the lowest value from T_(0) to T_(3)).Cardiac index and stroke volume index did not differ between groups,whereas systemic vascular resistance index was higher at T_(1–3) in the group R.These findings show that remimazolam,compared with propofol,better maintains hemodynamic stability during the induction,which may be attributed to its ability to better maintain systemic vascular resistance levels.展开更多
BACKGROUND Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging,especially for patients who do not respond well to endoscopy.In cases where patients have undergone an enterostomy,...BACKGROUND Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging,especially for patients who do not respond well to endoscopy.In cases where patients have undergone an enterostomy,the stenosis can be easily resolved through magnetic compression.However,common magnetic compre-ssion techniques cannot be performed on those without enterostomy.We design-ed a novel Y–Z deformable magnetic ring(Y–Z DMR)and successfully applied it to a patient with a stenosis rectal anastomosis and without enterostomy after rectal cancer surgery.CASE SUMMARY We here report the case of a 57-year-old woman who had undergone a laparo-scopic radical rectum resection(Dixon)for rectal cancer.However,she started facing difficulty in defecation 6 months after surgery.Her colonoscopy indicated stenosis of the rectal anastomosis.Endoscopic balloon dilation was performed six times on her.However,the stenosis still showed a trend of gradual aggravation.Because the patient did not undergo an enterostomy,the conventional endoscopic magnetic compression technique could not be performed.Hence,we imple-mented a Y–Z DMR implemented through the anus under single channel.The magnetic ring fell off nine days after the operation and the rectal stenosis was relieved.The patient was followed up for six months and reported good defeca-tion.CONCLUSION The Y–Z DMR deformable magnetic ring is an excellent treatment strategy for patients with rectal stenosis and without enterostomy.展开更多
Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hip...Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.展开更多
Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is o...Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.展开更多
Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains...Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.展开更多
BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple ...BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.展开更多
The National Natural Science Foundation of China is one of the major funding agencies for neuro rehabilitation research in China.This study reviews the frontier directions and achievements in the field of neurorehabil...The National Natural Science Foundation of China is one of the major funding agencies for neuro rehabilitation research in China.This study reviews the frontier directions and achievements in the field of neurorehabilitation in China and wo rldwide.We used data from the Web of Science Core Collection(WoSCC) database to analyze the publications and data provided by the National Natural Science Foundation of China to analyze funding information.In addition,the prospects for neurorehabilitation research in China are discussed.From 2010 to 2022,a total of 74,220 publications in neurorehabilitation were identified,with there being an overall upward tendency.During this period,the National Natural Science Foundation of China has funded 476 research projects with a total funding of 192.38 million RMB to support neuro rehabilitation research in China.With the support of the National Natural Science Foundation of China,China has made some achievements in neurorehabilitation research.Research related to neurorehabilitation is believed to be making steady and significant progress in China.展开更多
AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biolog...AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.展开更多
文摘Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses the law of large numbers and the central limit theorem to model to carry out the case study of FAHSYSU Simulation T,and takes measures of offsetting adverse selections to increase booking efficiency.The paper also analyzes how to apply the ancient Chinese theory that man is an integral part of nature to wipe out‘the market for lemons’.
基金The study was supported by a grant from Zhejiang Provincial Natural Science Foundation(LGF21H190004).
文摘To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic pancreatitis and pancreatic carcinoma,especially acinar cell carcinoma[1,2].The clinical manifestations are nonspecific erythema tender nodules.
文摘BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium.Timely medical contact is critical for successful AMI treatment,and delays increase the risk of death for patients.Pre-hospital delay time(PDT)is a significant challenge for reducing treatment times,as identifying high-risk patients with AMI remains difficult.This study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care,ultimately reducing PDT and improving treatment outcomes.AIM To construct a nomogram model for forecasting pre-hospital delay(PHD)likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD risk.METHODS A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September 2022.The study included 252 patients,with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 ratio.Independent risk factors influencing PHD were identified in the development group,leading to the establishment of a nomogram model for predicting PHD in patients with AMI.The model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation groups.RESULTS Independent risk factors for PHD in patients with AMI included living alone,hyperlipidemia,age,diabetes mellitus,and digestive system diseases(P<0.05).A characteristic curve analysis indicated area under the receiver operating characteristic curve values of 0.787(95%confidence interval:0.716–0.858)and 0.770(95%confidence interval:0.660-0.879)in the development and validation groups,respectively,demonstrating the model's good discriminatory ability.The Hosmer–Lemeshow goodness-of-fit test revealed no statistically significant disparity between the anticipated and observed incidence of PHD in both development and validation cohorts(P>0.05),indicating satisfactory model calibration.CONCLUSION The nomogram model,developed with independent risk factors,accurately forecasts PHD likelihood in AMI individuals,enabling efficient identification of PHD risk in these patients.
文摘Objective: To evaluate the role of prevention and control strategies for nosocomial infection in a tertiary teaching hospital during the sudden outbreak of Corona Virus Disease 2019 (COVID-19). Methods: The hospital initiated an emergency plan involving multi-departmental defense and control. It adopted a series of nosocomial infection prevention and control measures, including strengthening pre-examination and triage, optimizing the consultation process, improving the hospital’s architectural composition, implementing graded risk management, enhancing personal protection, and implementing staff training and supervision. Descriptive research was used to evaluate the short-term effects of these in-hospital prevention and control strategies. The analysis compared changes in related evaluation indicators between January 24, 2020 and February 12, 2020 (Chinese Lunar New Year’s Eve 2020 to lunar January 19) and the corresponding lunar period of the previous year. Results: Compared to the same period last year, the outpatient fever rate increased by 1.85-fold (P P Conclusion: The nosocomial infection prevention and control strategies implemented during this specific period improved the detection and control abilities for the COVID-19 source of infection and enhanced the compliance with measures. This likely contributed significantly to avoiding the occurrence of nosocomial infection.
基金supported by the 2020 Education and Teaching Reform Research Project of Xi’an Medical University,“Construction of‘Double-Qualified’Teachers in Affiliated Hospitals Based on‘Online Learning Platform for Clinical Teachers’and Construction and Practice of Quality Assurance System”(Project Number:2020JG-02)the 2021 Shaanxi Undergraduate and Higher Continuing Education Teaching Reform Research Project of Shaanxi Provincial Department of Education,“Construction of Teaching Staff Based on‘Online Learning Platform for Clinical Teachers of the First Affiliated Hospital of Xi’an Medical University’and Construction and Practice of Quality Assurance System”(Project Number:21BZ066).
文摘Objective:To build a set of teaching staff construction and teaching quality monitoring system suitable for clinical practice teaching in affiliated hospitals of medical colleges,achieve continuous improvement of clinical education and teaching level,and ensure the quality of medical education talent cultivation.Methods:A modern clinical practice teaching quality monitoring system is constructed based on organizational structure construction,teaching staff system construction,quality control system construction,and information platform construction,combined with external audit and evaluation.Results:The hospital has established a Faculty Development and Teaching Evaluation Office specifically responsible for the cultivation of clinical teachers and the evaluation and supervision of teaching quality.A relatively complete teacher construction and teaching quality monitoring system has also been established for clinical practice teaching,thus achieving integration with the school’s quality control system in terms of management mechanism.At the same time,a set of teaching quality control mode based on the“Internet+”platform has been created by means of informatization.At present,this mode has won three national computer software copyrights and two second prizes for school-level teaching achievements.Conclusion:Through five years of practice,an“Internet+”teaching quality evaluation and monitoring system with the characteristics of teaching hospitals affiliated to local medical colleges has been established.In order to further standardize the training system of clinical teachers in affiliated hospitals,achieve self-monitoring and self-improvement in terms of teaching quality,and ensure the continuous improvement of clinical teaching quality,we will continue to promote the development of clinical teachers with quality and excellence,enrich the main team of quality monitoring,guide the transformation of the education mode from being“centered on teachers”to being“centered on students,”and realize the integration of internal and external quality monitoring systems.
文摘To further improve the ability of pre-hospital and in-hospital collaborative treatment, strengthen emergency multidisciplinary cooperation and construct a scientific, rational and efficient emergency system, under the support of former chairman Yu Xue-zhong, Dr. Li Chun-sheng and numerous colleagues in the industry, the Emergency Medicine Society of the Chinese Medical Association appeal to us to draft Construction of Emergency and Pre-hospital Platform. Based on this background, the platform of emergency and pre-hospital first aid helps to build a 'one horizontal and one Longitudinal' treatment model, using the horizontal and longitudinal patterns to integrate emergency medical resources to satisfy the automatic information integration and intelligent analysis sharing, realizing the emergency management visualization and medical information digitization, simplifying the medical process and establishing a perfect standard for the emergent diseases, thereby ultimately achieving efficient diagnosis and scientific treatment.
文摘BACKGROUND Malignant peritoneal mesothelioma(MPeM)is a rare cancer with a poor prognosis at advanced stage,and the standard first-line treatment for inoperable patients is chemotherapy.Although combining programmed cell death 1(PD-1)inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors,there are few reports regarding initial immunochemotherapy in advanced MPeM.CASE SUMMARY Here,to our knowledge,we present the first case of a patient with epithelioid subtype MPeM,who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival(PFS)and good tolerance.A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen.Computed tomography revealed a solid mass in the lower abdomen,which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy.The patient received eight cycles of pemetrexed 800 mg(day 1),cisplatin 60/50 mg(day 1–2),and zimberelimab(PD-1 inhibitor)240 mg(day 1)every 3 wk.He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms.The best tumor response was partial remission with a final PFS of 7 mo.No immunerelated adverse event occurred during the combination treatment.CONCLUSION The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.
基金This research was supported by the following funds:Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173400001,KCXFZ20201221173411032,SGDX20210823103805042)Natural Science Fund of Guangdong Province(2021A1515010983)Shenzhen Key Medical Discipline Construction Fund(no.SZXK005).
文摘Background Somatic symptom disorder(SSD)commonly presents in general hospital settings,posing challenges for healthcare professionals lacking specialised psychiatric training.The Neuro-11 Neurosis Scale(Neuro-11)offers promise in screening and evaluating psychosomatic symptoms,comprising 11 concise items across three dimensions:somatic symptoms,negative emotions and adverse events.Prior research has validated the scale’s reliability,validity and theoretical framework in somatoform disorders,indicating its potential as a valuable tool for SSD screening in general hospitals.Aims This study aimed to establish the reliability,validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD.Through this comparative analysis,we aimed to validate the effectiveness and precision of the Neuro-11,enhancing its utility in clinical settings.Methods Between November 2020 and December 2021,data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People’s Hospital in China for various physical discomforts.The patients completed multiple questionnaires,including the Neuro-11,Short Form 36 Health Survey,Patient Health Questionnaire 15 items,Hamilton Anxiety Scale and Hamilton Depression Scale.Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD.Results The Neuro-11 demonstrated strong content reliability and structural consistency,correlating significantly with internationally recognised and widely used questionnaires.Despite its brevity,the Neuro-11 exhibited significant correlations with other questionnaires.A test-retest analysis yielded a correlation coefficient of 1.00,Spearman-Brown coefficient of 0.64 and Cronbach’sαcoefficient of 0.72,indicating robust content reliability and internal consistency.Confirmatory factor analysis confirmed the validity of the three-dimensional structure(p<0.001,comparative fit index=0.94,Tucker-Lewis index=0.92,root mean square error of approximation=0.06,standardised root mean square residual=0.04).The threshold of the Neuro-11 is set at 10 points based on the maximum Youden’s index from the receiver operating characteristic curve analysis.In terms of diagnostic efficacy,the Neuro-11 has an area under the curve of 0.67.
基金supported by the National Natural Science Foundation of China,No.81771355the Natural Science Foundation of Chongqing Science and Technology Bureau,Nos.CSTC2015jcyjA10096,cstc2021jcyj-msxmX0262(all to ZL)。
文摘Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.
基金supported by the Key Science and Technology Research of Henan Province,No.222102310351(to JW)Luoyang 2022 Medical and Health Guiding Science and Technology Plan Project,No.2022057Y(to JY)Henan Medical Science and Technology Research Program Province-Ministry Co-sponsorship,No.SBGJ202002099(to JY)。
文摘Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.
基金in part supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX)。
文摘The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).
基金supported by the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG02C(to Qiang Fang and SG)the National Natural Science Foundation of China,No.82201511(to SG)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515110873(to SG),2022A1515110139(to TW)the Medical Scientific Research Foundation of Guangdong Province,No.A2022077(to SG)。
文摘Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
文摘The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients.We used propofol at a rate of 60 mg/(kg·h)in the propofol group(group P)or remimazolam at a rate of 6 mg/(kg·h)in the remimazolam group(group R)for the induction.A processed electroencephalogram was used to determine whether the induction was successful and when to stop the infusion of the study drug.We measured when patients entered the operating room(T_(0)),when the induction was successful(T_(1)),and when before(T_(2))and 5 min after successful endotracheal intubation(T_(3)).We found that mean arterial pressure(MAP)was lower at T_(1–3),compared with T_(0) in both groups,but higher at T_(2) in the group R,whileΔMAP_(T0–T2) andΔMAP_(max) were smaller in the group R(ΔMAP_(T0–T2):the difference between MAP at time point T_(0) and T_(2),ΔMAP_(max):the difference between MAP at time point T_(0) and the lowest value from T_(0) to T_(3)).Cardiac index and stroke volume index did not differ between groups,whereas systemic vascular resistance index was higher at T_(1–3) in the group R.These findings show that remimazolam,compared with propofol,better maintains hemodynamic stability during the induction,which may be attributed to its ability to better maintain systemic vascular resistance levels.
基金Supported by Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University,No.2022MS-07and The Fundamental Research Funds for the Central Universities,No.xzy022023068.
文摘BACKGROUND Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging,especially for patients who do not respond well to endoscopy.In cases where patients have undergone an enterostomy,the stenosis can be easily resolved through magnetic compression.However,common magnetic compre-ssion techniques cannot be performed on those without enterostomy.We design-ed a novel Y–Z deformable magnetic ring(Y–Z DMR)and successfully applied it to a patient with a stenosis rectal anastomosis and without enterostomy after rectal cancer surgery.CASE SUMMARY We here report the case of a 57-year-old woman who had undergone a laparo-scopic radical rectum resection(Dixon)for rectal cancer.However,she started facing difficulty in defecation 6 months after surgery.Her colonoscopy indicated stenosis of the rectal anastomosis.Endoscopic balloon dilation was performed six times on her.However,the stenosis still showed a trend of gradual aggravation.Because the patient did not undergo an enterostomy,the conventional endoscopic magnetic compression technique could not be performed.Hence,we imple-mented a Y–Z DMR implemented through the anus under single channel.The magnetic ring fell off nine days after the operation and the rectal stenosis was relieved.The patient was followed up for six months and reported good defeca-tion.CONCLUSION The Y–Z DMR deformable magnetic ring is an excellent treatment strategy for patients with rectal stenosis and without enterostomy.
基金supported by the National Natural Science Foundation of China,No.91849104(to YW)。
文摘Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.
文摘Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.
基金Natural Science Foundation of Ningbo(Grant No.2021J261).
文摘Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.
基金Supported by the Key Medical Scientific and Technological Project of Henan Province,No.SBGJ202102188Henan Provincial Medical Science and Technology Project,No.LHGJ20221012the Key Project of Science and Technology of Xinxiang,No.GG2020027.
文摘BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.
文摘The National Natural Science Foundation of China is one of the major funding agencies for neuro rehabilitation research in China.This study reviews the frontier directions and achievements in the field of neurorehabilitation in China and wo rldwide.We used data from the Web of Science Core Collection(WoSCC) database to analyze the publications and data provided by the National Natural Science Foundation of China to analyze funding information.In addition,the prospects for neurorehabilitation research in China are discussed.From 2010 to 2022,a total of 74,220 publications in neurorehabilitation were identified,with there being an overall upward tendency.During this period,the National Natural Science Foundation of China has funded 476 research projects with a total funding of 192.38 million RMB to support neuro rehabilitation research in China.With the support of the National Natural Science Foundation of China,China has made some achievements in neurorehabilitation research.Research related to neurorehabilitation is believed to be making steady and significant progress in China.
基金Supported by the National Natural Science Foundation in China(No.81671641)Jiangsu Provincial Medical Innovation Team(No.CXTDA2017039)Gusu Health Talents Program(No.GSWS 2022018).
文摘AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.
