Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China. Integron, a conserved DNA sequence, which is carried on episomal genetic structures, plays a very importan...Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China. Integron, a conserved DNA sequence, which is carried on episomal genetic structures, plays a very important role in development of antibiotic resistance. This systematic analysis was based on MEDLINE and EMBASE databases. We summarized the distribution and proportion of different types of gene cassette arrays ofintegrons （including class 1, 2, 3 and atypical class 1 integron） from clinical bacteria isolates in China. Fifty-six literatures were included in this study. Most of the strains were Gram-negative bacteria （94.1%, 7,364/7,822） while only 5.9% strains were Gram- positive bacteria. Class 1 integrons were detected in 54.2% （3956/7295） Gram-negative strains, aadA2 was the most popular gene cassette array detected from 60 Gram-positive bacteria while dfrA 17-aadA5 were detected in 426 Gram- negative bacteria. This study identified 12 novel gene cassette arrays which have not been previously found in any species. All the novel gene cassette arrays were detected from Gram-negative bacteria. A regional characteristic of distribution of integrons was presented in this study. The results highlight a need for continuous surveillance of integrons and provide a guide for future research on integron-mediated bacteria resistance.展开更多
Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided i...Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided into the treatment group and the control group,each with 110 cases.Before treatment,there was no significant differences in age,sex,clinical symptoms,signs,laboratory tests and color Doppler ultrasound related examinations between the 2 groups(P>0.05).Among them,the treatment group on the basis of traditional Chinese and Western medicine treatment in our hospital,the Qi-acupuncture therapy of TCM was added.The extra meridian acupoints along with acupoints were selected.The control group received conventional treatment with traditional Chinese and Western medicine in our hospital.Results:There were significant differences in clinical symptoms,signs and chemistry between groups after treatment(P<0.01).There were significant differences in test,color ultrasound related examination and so on(P<0.01).Those in the treatment group was significantly better than the control group(P<0.01).Conclusion:On the basis of the Qi-acupuncture therapy of TCM,selecting extra meridian acupoint and acupoints can effectively treat PH.展开更多
BACKGROUND Mental disorders are common comorbidities among individuals with neurological diseases, and the prevalence of depressive and anxiety-related symptoms in newly referred patients at neurology outpatient clini...BACKGROUND Mental disorders are common comorbidities among individuals with neurological diseases, and the prevalence of depressive and anxiety-related symptoms in newly referred patients at neurology outpatient clinics is high. There have been few studies on the mental health of patients with late-onset myasthenia gravis(MG).AIM To examine the relationship between clinical features and the mental health symptoms within late-onset MG patients.METHODS A total of 105 patients diagnosed with MG were recruited consecutively from a neuromuscular outpatient clinic between December 2020 and February 2021. Patients were classified into two groups: early-onset MG(age at onset < 50 years, n = 63) and late-onset MG(age at onset ≥ 50 years, n = 42). Social demographic data and information about marital status, education level, clinical symptoms, serum antibody levels, and therapies used were collected for all participants. Participants were also evaluated using the Myasthenia Gravis Composite scale, the Myasthenia Gravis Activities of Daily Living scale, the Myasthenia Gravis Quality of Life 15(MG-QOL-15) questionnaire, the 17-item version of the Hamilton Depression Rating Scale(HAM-D) and the Hamilton Anxiety Rating Scale(HAM-A). The relationship between clinical features and mental health in late-onset MG patients was examined using multivariate logistic regression analyses.RESULTS Late-onset MG patients were more prone to dyspnea, had higher levels of serum anti-acetylcholine receptor antibodies, and higher total scores on the MG-QOL-15, HAM-D, and HAM-A questionnaires, than early-onset MG patients had(P < 0.05). Among those with late-onset MG, female patients had higher total HAM-D and HAM-A scores than male patients had(P < 0.05). High scores on the QOL-15 questionnaire were associated with higher incidences of anxiety and depression, and the association was found to be independent after adjusting for confounding risk factors. In the late-onset subgroup, the areas under the receiver operating characteristic curves for the MG-QOL-15 score-based diagnostic accuracy for anxiety and depression state were 0.816(P = 0.001) and 0.983(P < 0.001), respectively.CONCLUSION Higher MG-QOL-15 scores were a risk factor for anxiety and depression in late-onset MG, and women with late-onset MG were more likely to have anxiety and depression than men were.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterize...Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterized.This study aims to systematically explore the expression patterns,clinical significance,and immune-related functions of NUDT19 in various cancer types through multi-omics analysis,further revealing its potential role in cancer,particularly its functional and therapeutic target value in leukemia.Methods To achieve this goal,various bioinformatics approaches were employed to evaluate the expression patterns,clinical significance,and immune-related functions of NUDT19 in tumors and normal tissues.Additionally,we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications.Using the single-cell analysis tool SingleCellBase,we explored the distribution of NUDT19 across different cell subpopulations in tumors.To validate these findings,qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines,and we established acute myeloid leukemia(AML)cell lines(HL-60 and THP-1)to conduct NUDT19 knockdown and overexpression experiments,assessing its effects on leukemia cell proliferation,apoptosis,and invasion.Results Pan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types,which was closely associated with poor prognosis,clinical staging,and diagnostic markers.Furthermore,NUDT19 was significantly correlated with tumor biomarkers,immune-related genes,and immune cell infiltration in different cancers.Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes.Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells,suggesting its potentially diverse functional roles in different cell subpopulations.qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines.In AML cell lines,NUDT19 knockdown led to reduced cell proliferation and invasion,with increased apoptosis,while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis.Conclusion This study demonstrates the diverse roles of NUDT19 in various cancer types,with a particularly prominent functional role in leukemia.NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms.Our research highlights the potential of NUDT19 as a therapeutic target,particularly for targeted therapies in malignancies such as leukemia,with significant clinical application prospects.展开更多
Alcohol abuse constitutes a significant health hazard,leading to various organ damage,notably the liver and brain.Shanxi aged vinegar(SAV)is one of the famous fermented and functional foods containing a variety of bio...Alcohol abuse constitutes a significant health hazard,leading to various organ damage,notably the liver and brain.Shanxi aged vinegar(SAV)is one of the famous fermented and functional foods containing a variety of bioactive ingredients with beneficial effects on the human body.This study aimed to explore the potential protective effect of SAV in alleviating acute alcohol intoxication(AAI)in mice.It was found that SAV at 2.5 mL/kg BW effectively ameliorated the decline in behavioral abilities following alcohol consumption,characterized by a shortened sobering period.SAV reduces alcohol-induced liver damage by inhibiting hepatic function enzymes and oxidative stress levels.Additionally,SAV mitigated the overactivation of microglia and the downregulation of neurotransmitter levels including acetylcholinesterase(AchE),5-hydroxytryptamine(5-HT)and dopamine(DA),thereby reducing ethanol-induced brain damage.Meanwhile,SAV significantly decreased concentrations of alcohol and acetaldehyde in the blood and increased alcohol dehydrogenase(ADH)and acetaldehyde dehydrogenase(ALDH)activities in the liver,indicating enhancement of ethanol metabolism.Moreover,we found that some gut microbiota including Verrucomicrobiota,Akkermansia,and Enterococcus were downregulated after SAV treatment in mice with AAI.These bacteria showed a negative correlation with anti-oxidative markers(glutathione(GSH)and catalase(CAT))and enzymes related to ethanol metabolism pathways(ADH and ALDH),and a positive correlation with hepatic function markers(alanine aminotransferase(ALT),aspartate aminotransferase(AST),and malondialdehyde(MDA)),alcohol metabolites(alcohol and acetaldehyde)and neurotransmitters(AchE,5-HT,and DA).However,Bacteroidota,norank_f_Muribaculaceae,and Alistipes exhibited the opposite direction.These findings suggest that SAV possesses protective effects against hepatic and neuro-toxicity,and could be a potential functional food for AAI prevention.展开更多
Tumor heterogeneity and diversity significantly undermine the effectiveness of monotherapy.Collaborative therapy emerges as a promising approach to mitigate tumor recurrence resulting from monotherapy.Combining chemod...Tumor heterogeneity and diversity significantly undermine the effectiveness of monotherapy.Collaborative therapy emerges as a promising approach to mitigate tumor recurrence resulting from monotherapy.Combining chemodynamic therapy(CDT)with photothermal therapy(PTT)offers a compelling solution for eradicating residual tumor cells post-PTT.In this study,we harness the Fenton-like response facilitated by glucose oxidase(GOD)and the mild hyperthermia induced by polyethyleneimine(PEI)functionalized nitrogen-containing graphene oxide to enhance tumor therapy through a metal-free bionic nanozyme.GOD catalyzes a substantial amount of hydrogen peroxide,and,with the carrier's involvement,triggers a Fenton-like reaction,yielding a wealth of hydroxyl radicals.These hydroxyl radicals effectively target tumor cells following photothermal action,bolstering CDT and culminating in a bidirectional amplification treatment that effectively prevents tumor recurrence and metastasis.This research amalgamates the physical and chemical attributes of nanomaterials with the unique characteristics of the tumor microenvironment,presenting a compelling and efficacious alternative for tumor treatment.展开更多
BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can b...BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can be determined only in surgical specimens.Accurate preoperative prediction of MVI is conducive to clinical decisions.AIM To develop and validate a preoperative prediction model for MVI in patients with HCC.METHODS Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected.Then,the patients were nonrandomly split into a training cohort and a validation cohort.Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram.We evaluated the discrimination and calibration ability of the nomogram by using R software.RESULTS MVI was confirmed in 209(46.0%)patients by a pathological examination.Multivariate logistic regression analysis identified four risk factors independently associated with MVI:Tumor size[odds ratio(OR)=1.195;95%confidence interval(CI):1.107–1.290;P<0.001],number of tumors(OR=4.441;95%CI:2.112–9.341;P<0.001),neutrophils(OR=1.714;95%CI:1.036–2.836;P=0.036),and serumα-fetoprotein(20–400 ng/mL,OR=1.955;95%CI:1.055–3.624;P=0.033;>400 ng/mL,OR=3.476;95%CI:1.950–6.195;P<0.001).The concordance index was 0.79(95%CI:0.74–0.84)and 0.81(95%CI:0.74–0.89)in the training and validation cohorts,respectively.The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes.CONCLUSION We have developed and validated a preoperative prediction model for MVI in patients with HCC.The model could aid physicians in clinical treatment decision making.展开更多
Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. ...Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. The formation of new blood vessels ameliorates the local decrease in blood supply, enhancing the supply of oxygen and nutrients to newly-formed neurons. New blood vessels also act as a scaffold for the migration of neuroblasts to the infarct area after ischemic stroke. In light of this, researchers have been actively searching for methods to treat cerebral infarction. Netrins were first identified as a family of proteins that mediate axon guidance and direct axon migration during embryogenesis. Later studies have revealed other functions of this protein family. In this review, we focus on netrin-1, which has been shown to be involved in axon migration and angiogenesis, which are required for recovery after cerebral ischemia. Thus, therapies targeting netrin-1 may be useful for the treatment of ischemic stroke.展开更多
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have...Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.展开更多
BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and micro...BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and microscopic transsphenoidal approaches have been widely used in the resection of nonfunctional pituitary adenomas. However, the clinical efficacy in neuroendoscopic and microscopic surgery is still controversial. AIM To explore the clinical efficacy of neuroendoscopic and microscopic transsphenoidal approach for resection of nonfunctional pituitary adenomas. METHODS We retrospectively analyzed 251 patients with nonfunctional pituitary adenomas;138 underwent neuroendoscopic surgery via transsphenoidal approach, and 113 underwent microscopic surgery via transsphenoidal approach between July 2010 and September 2015. All patients were followed up for > 6 mo. Gender, age, course of disease, tumor diameter, tumor location, and percentage of patients with headache, visual impairment, sexual dysfunction, and menstrual disorders were contrasted between the two groups to compare the difference of preoperative data. Cure rate, symptom improvement rate, recurrence rate, the postoperative hospital stay, operating time, intraoperative blood loss, and the incidence of postoperative complications were compared in order to evaluate the advantages and disadvantages of neuroendoscopic and microscopic surgery.RESULTS There was no significant difference in cure rate, symptom improvement rate, and recurrence rate between neuroendoscopy group and microscopy group (82.6% vs 85.8%, P > 0.05;90.6% vs 93.8%, P > 0.05;5.1% vs 9.7%, P > 0.05). In the neuroendoscopy group, the postoperative hospital stay was 8.4 ± 0.6 d;operating time was 167.2 ± 9.6 min;intraoperative blood loss was 83.4 ± 9.3 mL, and the rates of diabetes insipidus and electrolyte imbalance were 4.3% and 8.0%, respectively. The corresponding results in the microscopic group were 11.2 ± 0.6 d, 199.7 ± 9.3 min, 138.8 ± 13.6 mL, and 32.7% and 20.4%, respectively. There were significant differences in postoperative hospital stay, operating time, intraoperative blood loss, and the rates of diabetes insipidus and electrolyte imbalance between the two groups (P < 0.05). CONCLUSION Neuroendoscopic and microscopic transsphenoidal approaches have similar clinical efficacy for the resection of nonfunctional pituitary adenomas. Neuroendoscopic surgery reduces operating time, intraoperative bleeding, postoperative recovery, and complications.展开更多
Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the un...Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.展开更多
BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we...BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level,which may better reflect the malignancy of rectal cancer.AIM To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer.METHODS We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012.These patients were randomly divided into two cohorts for cross-validation:training cohort and validation cohort.The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model.Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size.The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data.Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size.The primary and secondary outcomes were overall survival(OS)and disease-free survival(DFS),respectively.RESULTS In all,556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort(2/3 of 556,n=371)and the validation cohort(1/3 of 556,n=185).The cutoff was 2.429 ng/mL per cm.Comparison of the baseline data showed that high CEA/tumor size was correlated with older age,high TNM stage,the presence of perineural invasion,high CEA,and high carbohydrate antigen 19-9(CA 19-9).Kaplan-Meier curves showed a manifest reduction in 5-year OS(training cohort:56.7%vs 81.1%,P<0.001;validation cohort:58.8%vs 85.6%,P<0.001)and DFS(training cohort:52.5%vs 71.9%,P=0.02;validation cohort:50.3%vs 79.3%,P=0.002)in the high CEA/tumor size group compared with the low CEA/tumor size group.Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS(training cohort:hazard ratio(HR)=2.18,95%confidence interval(CI):1.28-3.73,P=0.004;validation cohort:HR=4.83,95%CI:2.21-10.52,P<0.001)as well as DFS(training cohort:HR=1.47,95%CI:0.93-2.33,P=0.096;validation cohort:HR=2.61,95%CI:1.38-4.95,P=0.003).CONCLUSION Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer.Higher CEA/tumor size is associated with worse OS and DFS.展开更多
Schisandra chinensis, a traditional Chinese medicine(TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been ...Schisandra chinensis, a traditional Chinese medicine(TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.展开更多
The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurre...The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).展开更多
BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining...BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.展开更多
Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in deter...Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated aminoglycoside resistance in Shigella. A systematic review was constructed based on MEDLINE and EMBASE databases. Randomeffect models or fixed-effect models were used based on P value considering the possibility of heterogeneity between studies for meta-analysis. Data manipulation and statistical analyses were performed using software STATA 11.0. By means of meta-analysis, we found a lower resistance to three kinds of aminoglycosides in the Europe-America areas during the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance was observed to be the most common drug resistance among Shigella isolates with a prevalence of 6.88% （95%CI： 6.36%-7.43%）. Comparison of data from Europe-America and Asia-Africa areas revealed that Shigella flexneri resistance was greater than the resistance calculated for Shigella sonnei. Importantly, Shigella sonnei has played a significant role in aminoglycoside-resistance in recent years. Similarly, data showed that resistance to these drugs in children was higher than the corresponding data of adults. In conclusion, aminoglycoside-resistant Shigella is not an unusual phenomenon worldwide. Distribution in Shigella resistance differs sharply based on geographic areas, periods of time and subtypes. The results from the present study highlight the need for con- tinuous surveillance of resistance and control of antibiotic usage.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金funded by the National Natural Science Foundation of China(No.81000754 and No. 81471994)received a grant from the Key Laboratory for Laboratory Medicine of Jiangsu Province of China(No.XK201114)
文摘Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China. Integron, a conserved DNA sequence, which is carried on episomal genetic structures, plays a very important role in development of antibiotic resistance. This systematic analysis was based on MEDLINE and EMBASE databases. We summarized the distribution and proportion of different types of gene cassette arrays ofintegrons （including class 1, 2, 3 and atypical class 1 integron） from clinical bacteria isolates in China. Fifty-six literatures were included in this study. Most of the strains were Gram-negative bacteria （94.1%, 7,364/7,822） while only 5.9% strains were Gram- positive bacteria. Class 1 integrons were detected in 54.2% （3956/7295） Gram-negative strains, aadA2 was the most popular gene cassette array detected from 60 Gram-positive bacteria while dfrA 17-aadA5 were detected in 426 Gram- negative bacteria. This study identified 12 novel gene cassette arrays which have not been previously found in any species. All the novel gene cassette arrays were detected from Gram-negative bacteria. A regional characteristic of distribution of integrons was presented in this study. The results highlight a need for continuous surveillance of integrons and provide a guide for future research on integron-mediated bacteria resistance.
基金Project of Research Plan of Traditional Chinese Medicine of Hebei Administration of Traditional Chinese Medicine(No.2019490)。
文摘Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided into the treatment group and the control group,each with 110 cases.Before treatment,there was no significant differences in age,sex,clinical symptoms,signs,laboratory tests and color Doppler ultrasound related examinations between the 2 groups(P>0.05).Among them,the treatment group on the basis of traditional Chinese and Western medicine treatment in our hospital,the Qi-acupuncture therapy of TCM was added.The extra meridian acupoints along with acupoints were selected.The control group received conventional treatment with traditional Chinese and Western medicine in our hospital.Results:There were significant differences in clinical symptoms,signs and chemistry between groups after treatment(P<0.01).There were significant differences in test,color ultrasound related examination and so on(P<0.01).Those in the treatment group was significantly better than the control group(P<0.01).Conclusion:On the basis of the Qi-acupuncture therapy of TCM,selecting extra meridian acupoint and acupoints can effectively treat PH.
基金Supported by the National Natural Science Foundation of China,No. 81873772 and 81971754National Natural Science Foundation Key International (Regional) Cooperation Research Project,No. 81620108010+3 种基金Clinical Study of 5010 Planned Project Sun Yat-sen University,No. 2010003Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases,No. 2020B1212060017Guangdong Provincial Clinical Research Center for Neurological Diseases,No. 2020B1111170002the Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases,No. 2015B050501003 and 2020A0505020004
文摘BACKGROUND Mental disorders are common comorbidities among individuals with neurological diseases, and the prevalence of depressive and anxiety-related symptoms in newly referred patients at neurology outpatient clinics is high. There have been few studies on the mental health of patients with late-onset myasthenia gravis(MG).AIM To examine the relationship between clinical features and the mental health symptoms within late-onset MG patients.METHODS A total of 105 patients diagnosed with MG were recruited consecutively from a neuromuscular outpatient clinic between December 2020 and February 2021. Patients were classified into two groups: early-onset MG(age at onset < 50 years, n = 63) and late-onset MG(age at onset ≥ 50 years, n = 42). Social demographic data and information about marital status, education level, clinical symptoms, serum antibody levels, and therapies used were collected for all participants. Participants were also evaluated using the Myasthenia Gravis Composite scale, the Myasthenia Gravis Activities of Daily Living scale, the Myasthenia Gravis Quality of Life 15(MG-QOL-15) questionnaire, the 17-item version of the Hamilton Depression Rating Scale(HAM-D) and the Hamilton Anxiety Rating Scale(HAM-A). The relationship between clinical features and mental health in late-onset MG patients was examined using multivariate logistic regression analyses.RESULTS Late-onset MG patients were more prone to dyspnea, had higher levels of serum anti-acetylcholine receptor antibodies, and higher total scores on the MG-QOL-15, HAM-D, and HAM-A questionnaires, than early-onset MG patients had(P < 0.05). Among those with late-onset MG, female patients had higher total HAM-D and HAM-A scores than male patients had(P < 0.05). High scores on the QOL-15 questionnaire were associated with higher incidences of anxiety and depression, and the association was found to be independent after adjusting for confounding risk factors. In the late-onset subgroup, the areas under the receiver operating characteristic curves for the MG-QOL-15 score-based diagnostic accuracy for anxiety and depression state were 0.816(P = 0.001) and 0.983(P < 0.001), respectively.CONCLUSION Higher MG-QOL-15 scores were a risk factor for anxiety and depression in late-onset MG, and women with late-onset MG were more likely to have anxiety and depression than men were.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
文摘Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterized.This study aims to systematically explore the expression patterns,clinical significance,and immune-related functions of NUDT19 in various cancer types through multi-omics analysis,further revealing its potential role in cancer,particularly its functional and therapeutic target value in leukemia.Methods To achieve this goal,various bioinformatics approaches were employed to evaluate the expression patterns,clinical significance,and immune-related functions of NUDT19 in tumors and normal tissues.Additionally,we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications.Using the single-cell analysis tool SingleCellBase,we explored the distribution of NUDT19 across different cell subpopulations in tumors.To validate these findings,qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines,and we established acute myeloid leukemia(AML)cell lines(HL-60 and THP-1)to conduct NUDT19 knockdown and overexpression experiments,assessing its effects on leukemia cell proliferation,apoptosis,and invasion.Results Pan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types,which was closely associated with poor prognosis,clinical staging,and diagnostic markers.Furthermore,NUDT19 was significantly correlated with tumor biomarkers,immune-related genes,and immune cell infiltration in different cancers.Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes.Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells,suggesting its potentially diverse functional roles in different cell subpopulations.qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines.In AML cell lines,NUDT19 knockdown led to reduced cell proliferation and invasion,with increased apoptosis,while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis.Conclusion This study demonstrates the diverse roles of NUDT19 in various cancer types,with a particularly prominent functional role in leukemia.NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms.Our research highlights the potential of NUDT19 as a therapeutic target,particularly for targeted therapies in malignancies such as leukemia,with significant clinical application prospects.
基金financially supported by the Natural Science Foundation of Tianjin(24JCYBJC01220)the Open Project Program of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-NF-202318)the foundation of Shanxi Provincial Key Laboratory for Vinegar Fermentation Science and Engineering,China(20220401931002).
文摘Alcohol abuse constitutes a significant health hazard,leading to various organ damage,notably the liver and brain.Shanxi aged vinegar(SAV)is one of the famous fermented and functional foods containing a variety of bioactive ingredients with beneficial effects on the human body.This study aimed to explore the potential protective effect of SAV in alleviating acute alcohol intoxication(AAI)in mice.It was found that SAV at 2.5 mL/kg BW effectively ameliorated the decline in behavioral abilities following alcohol consumption,characterized by a shortened sobering period.SAV reduces alcohol-induced liver damage by inhibiting hepatic function enzymes and oxidative stress levels.Additionally,SAV mitigated the overactivation of microglia and the downregulation of neurotransmitter levels including acetylcholinesterase(AchE),5-hydroxytryptamine(5-HT)and dopamine(DA),thereby reducing ethanol-induced brain damage.Meanwhile,SAV significantly decreased concentrations of alcohol and acetaldehyde in the blood and increased alcohol dehydrogenase(ADH)and acetaldehyde dehydrogenase(ALDH)activities in the liver,indicating enhancement of ethanol metabolism.Moreover,we found that some gut microbiota including Verrucomicrobiota,Akkermansia,and Enterococcus were downregulated after SAV treatment in mice with AAI.These bacteria showed a negative correlation with anti-oxidative markers(glutathione(GSH)and catalase(CAT))and enzymes related to ethanol metabolism pathways(ADH and ALDH),and a positive correlation with hepatic function markers(alanine aminotransferase(ALT),aspartate aminotransferase(AST),and malondialdehyde(MDA)),alcohol metabolites(alcohol and acetaldehyde)and neurotransmitters(AchE,5-HT,and DA).However,Bacteroidota,norank_f_Muribaculaceae,and Alistipes exhibited the opposite direction.These findings suggest that SAV possesses protective effects against hepatic and neuro-toxicity,and could be a potential functional food for AAI prevention.
基金financial support from the National Natural Science Foundation of China(Nos.82202354,U20A20338,82201247)The Summit Advancement Disciplines of Zhejiang Province(Wenzhou Medical University-Pharmaceutics)the Key R&D Program of Zhejiang Province(No.2021C04019)。
文摘Tumor heterogeneity and diversity significantly undermine the effectiveness of monotherapy.Collaborative therapy emerges as a promising approach to mitigate tumor recurrence resulting from monotherapy.Combining chemodynamic therapy(CDT)with photothermal therapy(PTT)offers a compelling solution for eradicating residual tumor cells post-PTT.In this study,we harness the Fenton-like response facilitated by glucose oxidase(GOD)and the mild hyperthermia induced by polyethyleneimine(PEI)functionalized nitrogen-containing graphene oxide to enhance tumor therapy through a metal-free bionic nanozyme.GOD catalyzes a substantial amount of hydrogen peroxide,and,with the carrier's involvement,triggers a Fenton-like reaction,yielding a wealth of hydroxyl radicals.These hydroxyl radicals effectively target tumor cells following photothermal action,bolstering CDT and culminating in a bidirectional amplification treatment that effectively prevents tumor recurrence and metastasis.This research amalgamates the physical and chemical attributes of nanomaterials with the unique characteristics of the tumor microenvironment,presenting a compelling and efficacious alternative for tumor treatment.
基金the National Natural Science Foundation of China,No.81672100the Key Laboratory for Laboratory Medicine of Jiangsu Province of China,No.ZDXKB2016005.
文摘BACKGROUND Microvascular invasion(MVI)is an important prognostic factor affecting early recurrence and overall survival in hepatocellular carcinoma(HCC)patients after hepatectomy and liver transplantation,but it can be determined only in surgical specimens.Accurate preoperative prediction of MVI is conducive to clinical decisions.AIM To develop and validate a preoperative prediction model for MVI in patients with HCC.METHODS Data from 454 patients with HCC who underwent hepatectomy at the First Affiliated Hospital of Nanjing Medical University between May 2016 and October 2019 were retrospectively collected.Then,the patients were nonrandomly split into a training cohort and a validation cohort.Logistic regression analysis was used to identify variables significantly associated with MVI that were then included in the nomogram.We evaluated the discrimination and calibration ability of the nomogram by using R software.RESULTS MVI was confirmed in 209(46.0%)patients by a pathological examination.Multivariate logistic regression analysis identified four risk factors independently associated with MVI:Tumor size[odds ratio(OR)=1.195;95%confidence interval(CI):1.107–1.290;P<0.001],number of tumors(OR=4.441;95%CI:2.112–9.341;P<0.001),neutrophils(OR=1.714;95%CI:1.036–2.836;P=0.036),and serumα-fetoprotein(20–400 ng/mL,OR=1.955;95%CI:1.055–3.624;P=0.033;>400 ng/mL,OR=3.476;95%CI:1.950–6.195;P<0.001).The concordance index was 0.79(95%CI:0.74–0.84)and 0.81(95%CI:0.74–0.89)in the training and validation cohorts,respectively.The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes.CONCLUSION We have developed and validated a preoperative prediction model for MVI in patients with HCC.The model could aid physicians in clinical treatment decision making.
基金supported by grants from the National Natural Science Foundation of China (81371276)Youth Project of the National Natural Science Foundation of China (81100871)Youth Teacher Training Project of Basic Scientific Research Grant of Sun Yat-sen University,China (13ykpy16)
文摘Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. The formation of new blood vessels ameliorates the local decrease in blood supply, enhancing the supply of oxygen and nutrients to newly-formed neurons. New blood vessels also act as a scaffold for the migration of neuroblasts to the infarct area after ischemic stroke. In light of this, researchers have been actively searching for methods to treat cerebral infarction. Netrins were first identified as a family of proteins that mediate axon guidance and direct axon migration during embryogenesis. Later studies have revealed other functions of this protein family. In this review, we focus on netrin-1, which has been shown to be involved in axon migration and angiogenesis, which are required for recovery after cerebral ischemia. Thus, therapies targeting netrin-1 may be useful for the treatment of ischemic stroke.
基金supported the National Natural Science Foundation of China,No.81974178(to CD).
文摘Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.
文摘BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and microscopic transsphenoidal approaches have been widely used in the resection of nonfunctional pituitary adenomas. However, the clinical efficacy in neuroendoscopic and microscopic surgery is still controversial. AIM To explore the clinical efficacy of neuroendoscopic and microscopic transsphenoidal approach for resection of nonfunctional pituitary adenomas. METHODS We retrospectively analyzed 251 patients with nonfunctional pituitary adenomas;138 underwent neuroendoscopic surgery via transsphenoidal approach, and 113 underwent microscopic surgery via transsphenoidal approach between July 2010 and September 2015. All patients were followed up for > 6 mo. Gender, age, course of disease, tumor diameter, tumor location, and percentage of patients with headache, visual impairment, sexual dysfunction, and menstrual disorders were contrasted between the two groups to compare the difference of preoperative data. Cure rate, symptom improvement rate, recurrence rate, the postoperative hospital stay, operating time, intraoperative blood loss, and the incidence of postoperative complications were compared in order to evaluate the advantages and disadvantages of neuroendoscopic and microscopic surgery.RESULTS There was no significant difference in cure rate, symptom improvement rate, and recurrence rate between neuroendoscopy group and microscopy group (82.6% vs 85.8%, P > 0.05;90.6% vs 93.8%, P > 0.05;5.1% vs 9.7%, P > 0.05). In the neuroendoscopy group, the postoperative hospital stay was 8.4 ± 0.6 d;operating time was 167.2 ± 9.6 min;intraoperative blood loss was 83.4 ± 9.3 mL, and the rates of diabetes insipidus and electrolyte imbalance were 4.3% and 8.0%, respectively. The corresponding results in the microscopic group were 11.2 ± 0.6 d, 199.7 ± 9.3 min, 138.8 ± 13.6 mL, and 32.7% and 20.4%, respectively. There were significant differences in postoperative hospital stay, operating time, intraoperative blood loss, and the rates of diabetes insipidus and electrolyte imbalance between the two groups (P < 0.05). CONCLUSION Neuroendoscopic and microscopic transsphenoidal approaches have similar clinical efficacy for the resection of nonfunctional pituitary adenomas. Neuroendoscopic surgery reduces operating time, intraoperative bleeding, postoperative recovery, and complications.
基金the technical support from National Key Clinical Department of Laboratory Medicine of Jiangsu Province Hospitalsupported by National Natural Science Foundation of China(No. 81272324,81371894)+1 种基金Key Laboratory for Medicine of Jiangsu Province of China(No.XK201114)project funded by the Priority Academic Program Development ofJiangsu Higher Education Institutions
文摘Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.
基金Supported by the National Basic Research Program of China(973Program)(No.2015CB554001,JW)the National Natural Science Foundation of China(No.81972245,YL+6 种基金 No.81902877,HY)the Natural Science Fund for Distinguished Young Scholars of Guangdong Province(No.2016A030306002,YL)the Tip-top Scientific and Technical Innovative Youth Talents of Guangdong special support program(No.2015TQ01R454,YL)the Project 5010 of Clinical Medical Research of Sun Yat-sen University-5010Cultivation Foundation(No.2018026,YL)the Natural Science Foundation of Guangdong Province(No.2016A030310222,HY No.2018A0303130303,HY)the Program of Introducing Talents of Discipline to Universities,and National Key Clinical Discipline(2012)
文摘BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level,which may better reflect the malignancy of rectal cancer.AIM To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer.METHODS We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012.These patients were randomly divided into two cohorts for cross-validation:training cohort and validation cohort.The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model.Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size.The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data.Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size.The primary and secondary outcomes were overall survival(OS)and disease-free survival(DFS),respectively.RESULTS In all,556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort(2/3 of 556,n=371)and the validation cohort(1/3 of 556,n=185).The cutoff was 2.429 ng/mL per cm.Comparison of the baseline data showed that high CEA/tumor size was correlated with older age,high TNM stage,the presence of perineural invasion,high CEA,and high carbohydrate antigen 19-9(CA 19-9).Kaplan-Meier curves showed a manifest reduction in 5-year OS(training cohort:56.7%vs 81.1%,P<0.001;validation cohort:58.8%vs 85.6%,P<0.001)and DFS(training cohort:52.5%vs 71.9%,P=0.02;validation cohort:50.3%vs 79.3%,P=0.002)in the high CEA/tumor size group compared with the low CEA/tumor size group.Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS(training cohort:hazard ratio(HR)=2.18,95%confidence interval(CI):1.28-3.73,P=0.004;validation cohort:HR=4.83,95%CI:2.21-10.52,P<0.001)as well as DFS(training cohort:HR=1.47,95%CI:0.93-2.33,P=0.096;validation cohort:HR=2.61,95%CI:1.38-4.95,P=0.003).CONCLUSION Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer.Higher CEA/tumor size is associated with worse OS and DFS.
基金supported by Guangzhou Clinical Research and Translational Centre for Major Neurological Diseases(No.201604020010)Natural Science Foundation of Guangdong Province(No.2015A030310255)
文摘Schisandra chinensis, a traditional Chinese medicine(TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.
基金This work was supported by the National Natural Science Foundation of China,Nos.81671240(to SZZ),81560220(to GHL)the Youth Science Foundation of Jiangxi Province of China,No.20151BAB215014(to GHL)Health and Family Planning Commission of Jiangxi Province of China,No.20195109(to GHL)。
文摘The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).
基金the Science and Technology Department of Zhejiang Province(No.2019C03029)the Bethune Charitable Foundation(No.G-X-2019-0101-12)+1 种基金the National Natural Science Foundation of China(Nos.81870510,81770719,81770752,and 81370851)the Zhejiang Provincial Natural Science Foundation of China(No.LQ18H050002)。
文摘BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.
基金funded by National Natural Science Foundation of China (No. 81000754)a grant from the Key Laboratory for Laboratory Medicine of Jiangsu Province of China (No. XK201114)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated aminoglycoside resistance in Shigella. A systematic review was constructed based on MEDLINE and EMBASE databases. Randomeffect models or fixed-effect models were used based on P value considering the possibility of heterogeneity between studies for meta-analysis. Data manipulation and statistical analyses were performed using software STATA 11.0. By means of meta-analysis, we found a lower resistance to three kinds of aminoglycosides in the Europe-America areas during the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance was observed to be the most common drug resistance among Shigella isolates with a prevalence of 6.88% （95%CI： 6.36%-7.43%）. Comparison of data from Europe-America and Asia-Africa areas revealed that Shigella flexneri resistance was greater than the resistance calculated for Shigella sonnei. Importantly, Shigella sonnei has played a significant role in aminoglycoside-resistance in recent years. Similarly, data showed that resistance to these drugs in children was higher than the corresponding data of adults. In conclusion, aminoglycoside-resistant Shigella is not an unusual phenomenon worldwide. Distribution in Shigella resistance differs sharply based on geographic areas, periods of time and subtypes. The results from the present study highlight the need for con- tinuous surveillance of resistance and control of antibiotic usage.
