The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted...The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.展开更多
BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I...BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.展开更多
Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryo...Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.展开更多
OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells wer...OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.展开更多
Objective:To systematically access the effects of integrated traditional Chinese and western medicine treatment versus western medicine treatment alone in glioma.Methods:Published randomized controlled trials were inc...Objective:To systematically access the effects of integrated traditional Chinese and western medicine treatment versus western medicine treatment alone in glioma.Methods:Published randomized controlled trials were included from electronic databases(Cochrane Library,Pubmed,Embase,Chinese National Knowledge Infrastructure,Wanfang database,Chinese Scientific Journal Database,Chinese Biomedical Literature Database.Deadline on January 30,2020).The Cochrane handbook was referred to evaluate the methodological quality.Curative efficacy,gastrointestinal side effects,bone marrow suppression,survival time and quality of life(Karnofsky)were compared between the two groups.Meta-analysis was conducted using Reveman 5.3 and Stata 14.0 software.Results:Twelve randomized controlled trials involved 886 cases were selected,including 446 cases in the trial group and 440 cases in the control group.The meta-analysis indicated that the overall efficacy of integrated traditional Chinese and western medicine showed significant improvement compared with western medicine alone.The effects included reduced tumor size(RR=1.32,95%CI(1.18,1.49),P<0.05),gastrointestinal adverse reactions(RR=0.42,95%CI(0.30,0.60),P<0.05),bone marrow suppression(RR=0.437,95%CI(0.282,0.677),P<0.05),and improved KPS score(SMD=0.632,95%CI(0.312,0.952),P<0.05).Conclusion:For patients with glioma,integrated traditional Chinese and western medicine treatment can be one of the options for a better treatment.展开更多
DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has sho...DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.展开更多
BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a the...BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.展开更多
As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by reg...As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.展开更多
Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effect...Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can infl uence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible infl uence of rejection on the risk of recurrent disease in the allograft.展开更多
AIM： To investigate the anti-inflammatory effects of asiatic acid（AA） on lipopolysaccharide（LPS）-induced inflammatory response in human corneal epithelial cells（HCECs）.METHODS： Cell viability was measured usin...AIM： To investigate the anti-inflammatory effects of asiatic acid（AA） on lipopolysaccharide（LPS）-induced inflammatory response in human corneal epithelial cells（HCECs）.METHODS： Cell viability was measured using a cell counting kit-8（CCK-8） assay.Quantitative real-time polymerase chain reaction（qR T-PCR） was used to determine the mR NA expression of interleukin-8（IL-8）,interleukin-6（IL-6）,interleukin-1β（IL-1β）,tumor necrosis factor-alpha（TNF-α）,and transforming growth factor-β（TGF-β） in HCECs.Intracellular reactive oxygen species（ROS） was measured using the ROS assay kit.Glutathione（GSH） concentration was measured using the total GSH assay kit.Akt1 and Akt phosphorylation（p-Akt1） levels were measured by Western blotting and immunofluorescence.RESULTS： AA induced toxicity at high concentrations and significantly stimulated the proliferation of HCECs at concentrations of 20 μmol/L for 1h.LPS at concentrations of 300 ng/mL for 1h significantly stimulated the mR NA expression of IL-8,IL-6,IL-1β,TNF-α,and TGF-β in HCECs,while the stimulation effects were significantly inhibited by AA（20 μmol/L）.In addition,AA was found to decrease the content of ROS,increase GSH generation,and also inhibit LPS-induced p-Akt in HCECs.CONCLUSION： AA decreases the generation of inflammatory factors IL-8,IL-6,IL-1β,TNF-α,and TGF-β in LPSstimulated HCECs.AA significantly inhibites the intracellular concentrations of ROS and increases GSH generation.AA also inhibites LPS-induced p-Akt in HCECs.These findings reveal that AA has anti-inflammation effects in LPS-stimulated HCECs.展开更多
Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in young and middle-aged women. Unlike other benign liv...Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in young and middle-aged women. Unlike other benign liver tumours, an HCA may be complicated by bleeding and malignant transformation. HCAs have been divided into four subtypes based on molecular and pathological features: hepatocyte nuclear factor 1α-mutated HCA, inflammatory HCA,β-catenin-mutated HCA, and unclassified HCA.β-cateninmutated HCA has the highest risk of haemorrhage or malignant transformation. In the latest upgrade of the guidelines regarding the management of benign liver tumours published in 2016 by the European Association for the Study of the Liver, magnetic resonance imaging (MRI) was recognized to be superior to all other imaging modalities in detecting HCAs and in being able to subtype HCAs up to 80%, with positive identification of 1α-mutated HCA or inflammatory HCA achievable with > 90% specificity. This review analyzed the imaging features of HCA using MRI with hepato-specific contrast agents, focusing on the limitations in the HCA characterization.展开更多
Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-l...Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.展开更多
BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of sever...BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.展开更多
Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies di...Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.展开更多
BACKGROUND Hepatitis C virus(HCV)infection is responsible for a chronic liver inflammation,which may cause end-stage liver disease and hepatocellular carcinoma.Apolipoprotein E(protein:ApoE,gene:APOE),a key player in ...BACKGROUND Hepatitis C virus(HCV)infection is responsible for a chronic liver inflammation,which may cause end-stage liver disease and hepatocellular carcinoma.Apolipoprotein E(protein:ApoE,gene:APOE),a key player in cholesterol metabolism,is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage.AIM To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation(OLT).METHODS This was a cohort study in which 179 patients,both genders and aged 34-70 years,were included before or after(up to 10 years follow-up)OLT.Liver injury severity was assessed using different criteria,including METAVIR and models for endstage liver disease.APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction.RESULTS The APOE3 allele was the most common(67.3%).In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant,the degree of severe inflammation(A3F4,0.0%)was significantly less frequent than in patients with minimal and moderate degree of inflammation(≤A2F4,16.2%)P=0.048,in patients carrying the APOE4 allele when compared to non-APOE4.In addition,a significant difference was also found(≤A2F4,64.4%vs A3F4,0.0%;P=0.043)and(A1F4,57.4%vs A3F4,0.0%;P=0.024)in APOE4 patients when compared to APOE3 carriers.The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis(F2)(P=0.006).CONCLUSION Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.展开更多
The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerv...The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome （n = 35） and group II with mild to moderate carpal tunnel syndrome （n = 47） according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.展开更多
The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MA...The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.展开更多
The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne ...The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne’s disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn’s disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the “MAP-hypothesis”, analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.展开更多
Aortic valve stenosis is the most common valve disease in the western world. Over the past few years the number of aortic valve replacement （AVR） interventions has increased with outcomes that have been improved des...Aortic valve stenosis is the most common valve disease in the western world. Over the past few years the number of aortic valve replacement （AVR） interventions has increased with outcomes that have been improved despite increasing age of patients and increasing bur- den of comorbidities. However, despite such excellent results and its well-established position, conventional AVR has undergone great de- velopment over the previous two decades. Such progress, by way of less irtvasive incisions and use of new technologies, including tran- scatheter aortic valve implantation and sutureless valve prostheses, is intended to reduce the traumatic impact of the surgical procedure, thus fulfilling lower risk patients＇ expectations on the one hand, and extending the operability toward increasingly high-risk patients on the other. Sutureless and rapid deployment aortic valves are biological, pericardial prostheses that anchor within the aortic annulus with no more than three sutures. The sutureless prostheses, by avoiding the passage and the tying of the sutures, significantly reduce operative times and may improve outcomes. However, there is still a paucity of robust, evidence-based data on the role and performance of sutureless AVR. Therefore, strongest long-term data, randomized studies and registry data are required to adequately assess the durability and long-term outcomes of sutureless aortic valve replacement.展开更多
AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional co...AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.展开更多
文摘The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.
文摘BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
基金supported by the National Natural Science Foundation of China (81772017 to[L.F.H.],and 82072106 and 32371371 to[A.R.Q.])The Project Supported by Natural Science Basic Research Plan in Shaanxi Province of China (2023-JC-YB-163 to[L.F.H.])the National Institutes of Health[AR-070135 and AG-056438 to W.C.,and AR075735,DE023813,AR074954,and DE028264 to Y.P.L.]。
文摘Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.
文摘OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.
基金National Natural Science Foundation of China(NO.81601754)Key Research and Development project of Shandong Province(2018GSF118141)。
文摘Objective:To systematically access the effects of integrated traditional Chinese and western medicine treatment versus western medicine treatment alone in glioma.Methods:Published randomized controlled trials were included from electronic databases(Cochrane Library,Pubmed,Embase,Chinese National Knowledge Infrastructure,Wanfang database,Chinese Scientific Journal Database,Chinese Biomedical Literature Database.Deadline on January 30,2020).The Cochrane handbook was referred to evaluate the methodological quality.Curative efficacy,gastrointestinal side effects,bone marrow suppression,survival time and quality of life(Karnofsky)were compared between the two groups.Meta-analysis was conducted using Reveman 5.3 and Stata 14.0 software.Results:Twelve randomized controlled trials involved 886 cases were selected,including 446 cases in the trial group and 440 cases in the control group.The meta-analysis indicated that the overall efficacy of integrated traditional Chinese and western medicine showed significant improvement compared with western medicine alone.The effects included reduced tumor size(RR=1.32,95%CI(1.18,1.49),P<0.05),gastrointestinal adverse reactions(RR=0.42,95%CI(0.30,0.60),P<0.05),bone marrow suppression(RR=0.437,95%CI(0.282,0.677),P<0.05),and improved KPS score(SMD=0.632,95%CI(0.312,0.952),P<0.05).Conclusion:For patients with glioma,integrated traditional Chinese and western medicine treatment can be one of the options for a better treatment.
基金funded by the National Natural Science Foundation of China, No. 81873924 (to QQL), No. 82171190 (to GHW)Nantong Science and Technology Project of China, No. MS22021010 (to LHS)High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China (to QQL)
文摘DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.
基金This study was approved by the Ethic Committee of Basic Medical College of Qingdao University(Approval No.QDWMkj-2020-012).
文摘BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.
基金supported by the Natural Science Foundation of China(Grant No.32071517,82072106)the Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2020JM-100).
文摘As a key coordinator of metabolism,AMP-activated protein kinase(AMPK)is vitally involved in skeletal muscle maintenance.AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle.AMPK is activated by phosphorylation and exerts its function as a kinase in many processes,including synthesis and degradation of proteins,mitochondrial biogenesis,glucose uptake,and fatty acid and cholesterol metabolism.Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease in muscle mass.The pathogenesis and therapeutic strategies of skeletal muscle atrophy are still under investigation.In this review,we discuss the role of AMPK in skeletal muscle metabolism and atrophy.We also discuss targeting AMPK for skeletal muscle treatment,including exercise,AMPK activators including 5-amino-4-imidazolecarboxamide ribonucleoside and metformin,and low-level lasers.These studies show the important roles of AMPK in regulating muscle metabolism and function;thus,the treatment of skeletal muscle atrophy needs to take into account the roles of AMPK.
文摘Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can infl uence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible infl uence of rejection on the risk of recurrent disease in the allograft.
基金Supported by Medical Program of Shandong Province(No.2014WS0441)Science and Technology Program of Shandong Province(No.2013YD21009)Innovative Team and Young Teachers Training Project of Qingdao Medical College(No.600201304)
文摘AIM： To investigate the anti-inflammatory effects of asiatic acid（AA） on lipopolysaccharide（LPS）-induced inflammatory response in human corneal epithelial cells（HCECs）.METHODS： Cell viability was measured using a cell counting kit-8（CCK-8） assay.Quantitative real-time polymerase chain reaction（qR T-PCR） was used to determine the mR NA expression of interleukin-8（IL-8）,interleukin-6（IL-6）,interleukin-1β（IL-1β）,tumor necrosis factor-alpha（TNF-α）,and transforming growth factor-β（TGF-β） in HCECs.Intracellular reactive oxygen species（ROS） was measured using the ROS assay kit.Glutathione（GSH） concentration was measured using the total GSH assay kit.Akt1 and Akt phosphorylation（p-Akt1） levels were measured by Western blotting and immunofluorescence.RESULTS： AA induced toxicity at high concentrations and significantly stimulated the proliferation of HCECs at concentrations of 20 μmol/L for 1h.LPS at concentrations of 300 ng/mL for 1h significantly stimulated the mR NA expression of IL-8,IL-6,IL-1β,TNF-α,and TGF-β in HCECs,while the stimulation effects were significantly inhibited by AA（20 μmol/L）.In addition,AA was found to decrease the content of ROS,increase GSH generation,and also inhibit LPS-induced p-Akt in HCECs.CONCLUSION： AA decreases the generation of inflammatory factors IL-8,IL-6,IL-1β,TNF-α,and TGF-β in LPSstimulated HCECs.AA significantly inhibites the intracellular concentrations of ROS and increases GSH generation.AA also inhibites LPS-induced p-Akt in HCECs.These findings reveal that AA has anti-inflammation effects in LPS-stimulated HCECs.
文摘Hepatocellular adenoma (HCA) is a rare benign liver tumour associated with the use of oral contraceptives or other steroid medications which occurs predominantly in young and middle-aged women. Unlike other benign liver tumours, an HCA may be complicated by bleeding and malignant transformation. HCAs have been divided into four subtypes based on molecular and pathological features: hepatocyte nuclear factor 1α-mutated HCA, inflammatory HCA,β-catenin-mutated HCA, and unclassified HCA.β-cateninmutated HCA has the highest risk of haemorrhage or malignant transformation. In the latest upgrade of the guidelines regarding the management of benign liver tumours published in 2016 by the European Association for the Study of the Liver, magnetic resonance imaging (MRI) was recognized to be superior to all other imaging modalities in detecting HCAs and in being able to subtype HCAs up to 80%, with positive identification of 1α-mutated HCA or inflammatory HCA achievable with > 90% specificity. This review analyzed the imaging features of HCA using MRI with hepato-specific contrast agents, focusing on the limitations in the HCA characterization.
基金Supported by AIRC/Start-Up(to Giovannetti E)Istituto Toscano Tumori ITT-2011(to Caparello C,Funel N,Vasile E and Giovannetti E)+2 种基金Regione Toscana“Fas Salute”(to Funel N and Giovannetti E)Bennink Foundation(to Meijer LL,Le Large TY,Giovannetti E and Kazemier G)CCA Foundation(to Giovannetti E)
文摘Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.
文摘BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.
基金supported by the National Natural Science Foundation of China ( 31570940,81772017)
文摘Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.
基金the National Council for Scientific and Technological Development,No.CNPqthe Coordination for the Improvement of Higher Education Personnel,No.CAPESthe Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico,No.FUNCAP.
文摘BACKGROUND Hepatitis C virus(HCV)infection is responsible for a chronic liver inflammation,which may cause end-stage liver disease and hepatocellular carcinoma.Apolipoprotein E(protein:ApoE,gene:APOE),a key player in cholesterol metabolism,is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage.AIM To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation(OLT).METHODS This was a cohort study in which 179 patients,both genders and aged 34-70 years,were included before or after(up to 10 years follow-up)OLT.Liver injury severity was assessed using different criteria,including METAVIR and models for endstage liver disease.APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction.RESULTS The APOE3 allele was the most common(67.3%).In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant,the degree of severe inflammation(A3F4,0.0%)was significantly less frequent than in patients with minimal and moderate degree of inflammation(≤A2F4,16.2%)P=0.048,in patients carrying the APOE4 allele when compared to non-APOE4.In addition,a significant difference was also found(≤A2F4,64.4%vs A3F4,0.0%;P=0.043)and(A1F4,57.4%vs A3F4,0.0%;P=0.024)in APOE4 patients when compared to APOE3 carriers.The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis(F2)(P=0.006).CONCLUSION Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.
文摘The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome （n = 35） and group II with mild to moderate carpal tunnel syndrome （n = 47） according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.
基金supported by the National Natural Science Foundation of China ( 81772017,31570940)Young Talent Fund of University Association for Science and Technology in Shaanxi,China ( 20170401)Supported by Natural Science Basic Research Plan in Shaanxi Province of China ( 2018JM3040)
文摘The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.
文摘The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne’s disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn’s disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the “MAP-hypothesis”, analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.
文摘Aortic valve stenosis is the most common valve disease in the western world. Over the past few years the number of aortic valve replacement （AVR） interventions has increased with outcomes that have been improved despite increasing age of patients and increasing bur- den of comorbidities. However, despite such excellent results and its well-established position, conventional AVR has undergone great de- velopment over the previous two decades. Such progress, by way of less irtvasive incisions and use of new technologies, including tran- scatheter aortic valve implantation and sutureless valve prostheses, is intended to reduce the traumatic impact of the surgical procedure, thus fulfilling lower risk patients＇ expectations on the one hand, and extending the operability toward increasingly high-risk patients on the other. Sutureless and rapid deployment aortic valves are biological, pericardial prostheses that anchor within the aortic annulus with no more than three sutures. The sutureless prostheses, by avoiding the passage and the tying of the sutures, significantly reduce operative times and may improve outcomes. However, there is still a paucity of robust, evidence-based data on the role and performance of sutureless AVR. Therefore, strongest long-term data, randomized studies and registry data are required to adequately assess the durability and long-term outcomes of sutureless aortic valve replacement.
文摘AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.
