Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Value of combining the serum D-lactate, diamine oxidase, and endotoxin levels to predict gut-derived infections in cancer patients

Objective:This is a retrospective observational cohort study.The objective of this retrospective observational cohort study was to evaluate the value of the combined serum D-lactic acid,diamine oxidase(DAO),and endotoxin levels to predict intestinal barrier impairment and gut-derived infection(GDI)in cancer patients.Methods:Cancer patients receiving chemotherapy or palliative care treatment at our hospital were enrolled in the study.The serum concentrations of DAO,D-lactic acid,and endotoxin were determined using the intestinal barrier function biochemical index analysis system.The patients'infection information came from the hospital's Medicom Prescription Automatic Screening System and themedical records.Three hundred fifty-three cancer patients were included in the study(53.8%female,73.7%cancer stage IV,27.8%had bowel obstruction).Results:The total incidence of GDI was 33.4%(118/353).The median length of hospital stay was 16 days for patients with GDI,compared with 7 days for patients without GDI(P<0.001).The media hospitalization costs were¥27,362.35 for patients with GDI compared with¥11,614.08 for patients without GDI(P<0.001).The serum concentrations of DAO,D-lactic acid,and endotoxin were significantly higher in patients with GDI.As malignant bowel obstruction(MBO)worsened,the concentrations of DAO,D-lactic acid,and endotoxin increased.Multivariate logistic regression models revealed that the DAO,endotoxin,IL-6,and C-reactive protein levels were significantly associated with an increased risk of GDI.In addition,we also found a fivefold increased risk of infection in patients withMBO compared with those without bowel obstruction(OR=6.210,P<0.001).All of the areas under the receiver operating characteristic curve(AUCs)for DAO,D-lactate,and endotoxin to predict GDI were<0.7(AUC=0.648,P<0.001;AUC=0.624,P<0.01;AUC=0.620,P<0.01,respectively).However,when the parameters were combined(DAO+D-lactate+endotoxin),the predictive power increased significantly(AUC=0.797,P<0.001).Moreover,combining these intestinal barrier indicators and the presence of MBO had better power to predict GDI than either alone(AUC=0.837,P<0.001).Conclusions:Combining the serum DAO,D-lactic acid,and endotoxin levels was a better predictor of GDI than any of the indicators alone,and combining these with the diagnosis of MBO could further improve the efficacy for predicting GDI.

Extension Protocol for the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC)Study:2021 update

Background Malnutrition is common in patients with cancer,and this adversely affects the survival and quality of life of patients.Chinese Society for Nutritional Oncology issued a multi-center,large-scale,long-term follow-up prospective study,the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC study)since 2013.This is an extension to the previous 2013-2020 study protocol.This study still sought to:①address the prognostic impact of nutritional factors and quality of life on cancer patient survival;②describe the overall and cancer-specific incidence and/or distribution of malnutrition and different measurements of patient quality of life.Methods and study design This is an observational,multi-centered,hospital-based prospective cohort study.Data collection will be performed at baseline(within 48 hours after patient admission),during the hospital stay and 30 days after hospital admission.Follow-up will be conducted for 1-20 years after enrollment.The primary outcome will be the all-cause mortality/overall survival,and secondary outcomes will be the length of hospital stay and costs of hospitalization.Study factors will include demographic characteristics,tumor characteristics,information about chronic diseases,hematological measurements(e.g.,red blood cell count,total lymphocyte counts,hemoglobin,albumin,prealbumin,creatinine,C-reactive protein,IL-6),anthropometric measurements(e.g.,height,weight,arm circumference,arm muscle circumference,triceps skinfold thickness,and waist circumference),body composition parameters,PG-SGA scores,quality of life(as indicated by the QLQ-C30 questionnaire),muscle mass(as indicated by the calf circumference),muscle strength(as indicated by the handgrip strength),muscle function(as indicated by the six-meter walking speed test)and physical status assessments(as indicated by the Karnofsky Performance Status scores).This clinical study protocol was approved by local Ethics Committees of all the participating hospitals.Written informed consent is required for each subject included.Discussion This multi-center,large-scale,long-term follow up prospective study will help improve the diagnosis of malnutrition in cancer patients and identify the risk factors associated with adverse clinical outcomes.The anticipated results of this study will highlight the need for a truly scientific appraisal of nutrition therapy in Chinese oncology populations,and finally help treat the potentially reversible elements of malnutrition in cancer patients to improve their clinical outcomes in the future.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt

BACKGROUND Skeletal muscle abnormalities,such as muscle mass depletion(sarcopenia)and fatty infiltration of the muscle(myosteatosis),are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt(TIPS).AIM To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy(HE)and mortality after TIPS.METHODS The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved.The transversal psoas muscle thickness(TPMT)and psoas muscle attenuation(PMA)measured from the unenhanced abdominal computed tomography(CT)at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis,respectively.The area under curve(AUC)was used to evaluate the discriminative power of TPMT,PMA,and relevant clinical parameters.Furthermore,log-rank test was performed to compare the incidence of overt HE and survival between the different groups,and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models.RESULTS A total of 108 patients were collected.Among these patients,45.4%of patients developed overt HE after TIPS treatment.Furthermore,32.4%and 28.7%of these patients were identified to have myosteatosis and sarcopenia,respectively.Myosteatosis(51.0%vs 16.9%,P<0.001)and sarcopenia(40.8 vs 18.6%,P=0.011)were found to be more frequent in patients with overt HE,when compared to patients without overt HE.The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE(AUC=0.713 and 0.778,respectively)was higher when compared to the neutrophil lymphocyte ratio(AUC=0.636).The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis,followed by patients with myosteatosis or sarcopenia,while this was the lowest in patients without sarcopenia and myosteatosis.In addition,sarcopenia and myosteatosis were independently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients.CONCLUSION CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.

Application of non-mydriatic fundus photography-assisted telemedicine in diabetic retinopathy screening

BACKGROUND Early screening and accurate staging of diabetic retinopathy(DR)can reduce blindness risk in type 2 diabetes patients.DR’s complex pathogenesis involves many factors,making ophthalmologist screening alone insufficient for prevention and treatment.Often,endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early intervention.AIM To explore the efficacy of non-mydriatic fundus photography(NMFP)-enhanced telemedicine in assessing DR and its various stages.METHODS This retrospective study incorporated findings from an analysis of 93 diabetic patients,examining both NMFP-assisted telemedicine and fundus fluorescein angiography(FFA).It focused on assessing the concordance in DR detection between these two methodologies.Additionally,receiver operating characteristic(ROC)curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine,using FFA outcomes as the standard benchmark.RESULTS In the context of DR diagnosis and staging,the kappa coefficients for NMFPassisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively,indicating substantial intermethod agreement.Moreover,the NMFP-assisted telemedicine’s predictive accuracy for positive FFA outcomes,as denoted by the area under the ROC curve,was remarkably high at 0.955,within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than 0.001.This predictive model exhibited a specificity of 100%,a sensitivity of 90.9%,and a Youden index of 0.909.CONCLUSION NMFP-assisted telemedicine represents a pragmatic,objective,and precise modality for fundus examination,particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic patients.Its implementation in these scenarios is of paramount significance,enhancing the clinical accuracy in the diagnosis and therapeutic management of DR.This methodology not only streamlines patient evaluation but also contributes substantially to the optimization of clinical outcomes in DR management.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

Experimental and numerical study of the effect of pulsatile flow on wall displacement oscillation in a flexible lateral aneurysm model

This study experimentally and numerically investigated the effect of pulsatile flow of different frequencies and outflow resistance on wall deformation in a lateral aneurysm.A method for constructing a flexible aneurysm model was developed,and a self-designed piston pump was used to provide the pulsatile flow conditions.A fluid-structure interaction simulation was applied for comparison with and analysis of experimental findings.The maximum wall displacement oscillation increased as the pulsation frequency and outflow resistance increased,especially at the aneurysm dome.There is an obvious circular motion of the vortex center accompanying the periodic inflow fluctuation,and the pressure at the aneurysm dome at peak flow increased as the pulsatile flow frequency and terminal flow resistance increased.These results could explain why abnormal blood flow with high frequency and high outflow resistance is one of the risk factors for aneurysm rupture.

Mechanisms and status of research on the protective effects of traditional Chinese medicine against ischemic brain injury

Ischemic brain injury occurs when the metabolic needs of brain tissue cannot be met due to insufficient blood supply to the brain.It is one of the main causes of death and adult disability worldwide.The recurrence rate of ischemic brain injury is high.It places a heavy economic burden on families and society,and seriously affects human health and quality of life.In traditional Chinese medicine,ischemic stroke belongs to the category of“stroke”.The use of traditional Chinese medicine to treat stroke has a long history.After years of experimental research,a large amount of theoretical knowledge and practical experience have been accumulated.Promoting blood circulation and removing blood stasis is the basis of traditional Chinese medicine theory on the treatment of ischemic stroke.Commonly used single Chinese medicines include Chuangxiong(Ligusticum chuanxiong hort),Danggui(Angelica sinensis),Danshen(Salvia miltiorrhiza Bunge),Honghua(Carthamus tinctorius L.),Mudanpi(Moutan Cortex),and Huangqi(Astragali Radix).Buyang Huanwu decoction,Xinglou Chengqi decoction,Taohong Siwu decoction,and other traditional Chinese medicine prescriptions are believed to have a protective effect against brain damage caused by ischemic stroke.With the development of modern medical technology,the mechanism of traditional Chinese medicine treatments for ischemic brain injury has gradually been explored.This article reviews the mechanisms of traditional Chinese medicine’s protection against ischemic brain injury and its current clinical application.

Quadrilateral plate fractures of the acetabulum:Classification,approach,implant therapy and related research progress

The quadrilateral plate(QP)is an essential structure of the inner wall of the acetabulum,an important weight-bearing joint of the human body,which is often involved in acetabular fractures.The operative exposure,reduction and fixation of QP fractures have always been the difficulties in orthopedics due to the special morphological structure and anatomical features of the QP.Fortunately,there have been many effective methods and instruments developed for QP exposure,reduction and fixation by virtue of the combined efforts of numerous orthopedists.At the same time,each method presents with its own advantages and disadvantages,resulting in different prognoses.It is necessary to have a thorough understanding of the anatomy,radiology and fixation techniques of the QP in terms of patient prognosis optimization.In this paper,the anatomical features,definition and classification of QP,operative approach selection,implant internal fixation methods and efficacy were reviewed.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome:A study from China

BACKGROUND Functional constipation(FC)and constipation-predominant irritable bowel syndrome(IBS-C)represent a spectrum of constipation disorders.However,the majority of previous clinical investigations have focused on Western populations,with limited data originating from China.AIM To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population.METHODS Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled.FC and IBS-C diagnoses were established using ROME IV criteria,and patients underwent high-resolution anorectal manometry(ARM)and a colonic transmit test using the Sitz marker study.Constipation-related symptoms were obtained through questionnaires.Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21.The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared.RESULTS No significant differences in sex,age or abdominal discomfort symptoms were observed between IBS-C and FC patients(all P>0.05).The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC(36.63%vs 15.91%,P<0.05),while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group(50%vs 26.73%,P<0.05).Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM.IBS-C patients were found to have a higher prevalence of depression than FC patients(66.30%vs 42.42%,P<0.05).The scores for feelings of guilt,suicide,psychomotor agitation,diurnal variation,obsessive/compulsive disorder,hopelessness,self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients(P<0.05).For IBS-C(χ^(2)=5.438,P<0.05)but not FC,patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time.For IBS-C patients but not FC patients,the threshold of first constant sensation,desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety(r=0.414,r=0.404,and r=0.418,respectively,P<0.05).The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression(69.6%vs 41.9%,χ2=4.054,P<0.05).CONCLUSION Our findings highlight both overlapping and distinctive patterns of colon transit,dyssynergic patterns,anorectal sensation,psychological distress,and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population,providing valuable insights into the pathophysiological underpinnings of these disorders.

Novel roles of lipopolysaccharide and TLR4/NF-κB signaling pathway in inflammatory response to liver injury in Budd-Chiari syndrome

BACKGROUND Budd-Chiari syndrome(BCS)is an uncommon disorder characterized by obstruction of hepatic venous outflow.To date,the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown.AIM To assess the role of NF-κB-mediated inflammation in BCS-induced liver injury in humans and rats.METHODS A total of 180 rats were randomly assigned into nine groups,including four BCS model groups(1,3,6 and 12 wk),four sham-operated groups(1,3,6 and 12 wk),and a control group.Lipopolysaccharide(LPS)levels in each group were detected by the Tachypleus Amebocyte Lysate assay.The mRNA and protein levels of TLR4,NF-κB,tumor necrosis factor(TNF)-α,interleukin(IL)-2 and interferon(IFN)-γwere quantified.In addition,60 patients with BCS and 30 healthy controls were enrolled,and their blood samples were analyzed.RESULTS Hepatic and plasma LPS levels were significantly increased in rats.The mRNA and protein expression levels of TLR4,NF-κB and inflammatory cytokines(TNF-α,IL-2 and IFN-γ)in liver tissues were significantly higher in the BCS model groups compared with the other two groups.In addition,the model groups(1,3,6 and 12 wk after BCS induction)showed significant differences in the levels of LPS,TLR4,NF-κB,TNF-α,IL-2 and IFN-γ.Notably,there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4,NF-κB and inflammatory cytokines.Importantly,it was revealed that the levels of LPS,TLR4,NF-κB and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients.CONCLUSION LPS level is markedly elevated in BCS,in turn activating the TLR4/NF-κB signaling pathway,leading to induction of inflammatory cytokines(TNF-α,IL-2 and IFN-γ)in response to BCS-induced liver injury.

Online calculator for predicting the risk of malignancy in patients with pancreatic cystic neoplasms: A multicenter, retrospective study

BACKGROUND Efficient and practical methods for predicting the risk of malignancy in patients with pancreatic cystic neoplasms(PCNs)are lacking.AIM To establish a nomogram-based online calculator for predicting the risk of malignancy in patients with PCNs.METHODS In this study,the clinicopathological data of target patients in three medical centers were analyzed.The independent sample t-test,Mann–Whitney U test or chi-squared test were used as appropriate for statistical analysis.After univariable and multivariable logistic regression analysis,five independent factors were screened and incorporated to develop a calculator for predicting the risk of malignancy.Finally,the concordance index(C-index),calibration,area under the curve,decision curve analysis and clinical impact curves were used to evaluate the performance of the calculator.RESULTS Enhanced mural nodules[odds ratio(OR):4.314;95%confidence interval(CI):1.618–11.503,P=0.003],tumor diameter≥40 mm(OR:3.514;95%CI:1.138–10.849,P=0.029),main pancreatic duct dilatation(OR:3.267;95%CI:1.230–8.678,P=0.018),preoperative neutrophil-to-lymphocyte ratio≥2.288(OR:2.702;95%CI:1.008–7.244,P=0.048],and preoperative serum CA19-9 concentration≥34 U/mL(OR:3.267;95%CI:1.274–13.007,P=0.018)were independent risk factors for a high risk of malignancy in patients with PCNs.In the training cohort,the nomogram achieved a C-index of 0.824 for predicting the risk of malignancy.The predictive ability of the model was then validated in an external cohort(C-index:0.893).Compared with the risk factors identified in the relevant guidelines,the current model showed better predictive performance and clinical utility.CONCLUSION The calculator demonstrates optimal predictive performance for identifying the risk of malignancy,potentially yielding a personalized method for patient selection and decision-making in clinical practice.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca^2+-STIM1/Orail Signaling

Summary:Dexmedetomidine(DEX),a potent and highly selective agonist for a2-adrenergic receptors(a2AR),exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca^2+influx.However,the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation(OGD/R)injury in vitro are unknown.We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells,as evidenced by decreased oxidative stress,autophagy,and neuronal apoptosis.Specifically,DEX pretreatment decreased the expression levels of stromal interaction molecule 1(STIM1)and calcium release-activated calcium channel protein 1(Orail),and reduced the concentration of intracellular calcium pools.In addition,variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions,which were modulated through STIM 1/Orail signaling.Moreover,DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3(LC3),hallmark markers of autophagy,and the formation of autophagosomes.In conclusion,these results suggested that DEX exerts neuroprotective effects against oxidative stress,autophagy,and neuronal apoptosis afier OGD/R injury via modulation of Caf-STIM1/Orai1 signaling.Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.

Influence of Clip Locations on Intraaneurysmal Flow Dynamics in Patient-specific Anterior Communicating Aneurysm Models with Different Aneurysmal Angle

To improve aneurysm treatment,this study examined the influence of clip locations on hemodynamic factors in patient-specific anterior communicating artery(ACoA)aneurysms with different aneurysmal angle.We proposed a simplified classification of ACoA aneurysms using aneurysmal angle,defined by the angle of pivot of the aneurysmal dome and the virtual two-dimensional plane created by both proximal A2 segments of anterior cerebral artery(ACA).ACoA aneurysms with three different aneurysmal angles,which are 15°,80°and 120°,were analyzed in our study.In this work,we obtained hemodynamics before and after clipping surgery with three clip locations based on clinical clipping strategies in three ACoA aneurysms with different aneurysm angles.Results showed that local high pressure occurs at impingement region of the ACoA aneurysm before clipping and new impingement region close to the clipping location after clipping treatment.For clipping the aneurysm with aneurysmal angle 15°and a wide neck,wall shear stress(WSS)distribution is more uniform when the clipping angle of two clips close to 180°comparing with other two angles.In addition,for clipping the aneurysm with aneurysmal angle 80°and 120°,local high pressure appears on new impingement region and high WSS distributes around the clipping location when the clip plane is normal to the direction of inflow of aneurysm from the dominance of A1 segment of ACA.Hence,we should avoid the impingement of inflow from the A1 segment and choose a favorable clipping location for the fastness of clip.The results of our study could preoperatively give a useful information to the decision of surgical plan.

Nomogram based on inflammation-related markers for predicting survival of patients undergoing hepatectomy for hepatocellular carcinoma

BACKGROUND Previous nomograms for hepatocellular carcinoma(HCC)did not include the neutrophil-to-lymphocyte ratio(NLR)or platelet-to-lymphocyte ratio(PLR).This study aimed to establish an effective nomogram capable of estimating the association between preoperative inflammatory factors and overall survival(OS)of HCC patients after hepatectomy.AIM To analyse the factors affecting the prognosis of HCC and establish a nomogram.METHODS A total of 626 HCC patients(410 training set patients from the First Affiliated Hospital of Anhui Medical University and 216 validation set patients from the First Affiliated Hospital of University of Science and Technology of China)underwent hepatectomy from January 2014 to December 2017 and were followed up every 3–6 mo.The nomogram was based on OS-related independent risk factors identified by Cox regression analysis.The C-index,calibration curve,and area under the curve(AUC)were used to evaluate the nomogram’s accuracy.RESULTS The 1-,2-and 3-year OS rates were 79.0%,68.0%and 45.4%in the training cohort(median OS=34 mo)and 92.1%,73.9%and 51.2%in the validation cohort(median OS=38 mo).Higherα-fetoprotein[hazard ratio(HR)=1.812,95%confidence interval(CI):1.343–2.444],NLR(HR=2.480,95%CI:1.856–3.312)and PLR(HR=1.974,95%CI:1.490–2.616),tumour size≥5 cm(HR=1.323,95%CI:1.002–1.747),and poor differentiation(HR=3.207,95%CI:1.944–5.290)were significantly associated with shortened OS.The developed nomogram integrating these variables showed good reliability in both the training(C-index=0.71)and validation cohorts(C-index=0.75).For predicting 1-,2-and 3-year OS,the nomogram had AUCs of 0.781,0.743 and 0.706 in the training cohort and 0.789,0.815 and 0.813 in the validation cohort.The nomogram was more accurate in predicting prognosis than the AJCC TNM staging system.CONCLUSION The prognostic nomogram combining pathological characteristics and inflammation indicators could provide a more accurate individualized risk estimate for the OS of HCC patients with hepatectomy.

Cluster headache due to structural lesions: A systematic review of published cases

BACKGROUND Cluster headache(CH)is a severe incapacitating headache disorder.By definition,its diagnosis must exclude possible underlying structural conditions.AIM To review available information on CLH caused by structural lesions and to provide better guides in the distinguishing process and to ensure that there is not a potentially treatable structural lesion.METHODS We conducted a systematic review of 77 published cases of symptomatic CH and cluster-like headache(CLH)in PubMed and Google Scholar databases.RESULTS Structural pathologies associated with CH were vascular(37.7%),tumoral(32.5%)and inflammatory(27.2%).Brain mass-like lesions(tumoural and inflammatory)were the most common diseases(28.6%),among which 77.3%lesions were at the suprasellar(pituitary)region.Cases of secondary CH related to sinusitis rose dramatically,occupying 19.5%.The third most common disease was internal carotid artery dissection,accounting for 14.3%.Atypical clinical features raise an early suspicion of a secondary cause:Late age at onset and eye and retroorbital pains were common conditions requiring careful evaluation and were present in at least one-third of cases.Abnormal neurological examination was the most significant red flag for impaired cranial nerves.CLH patients may be responsive to typical CH treatments;therefore,the treatment response is not specific.CLH can be triggered by contralateral structural pathologies.CLH associated with sinusitis and cerebral venous thrombosis required more attention.CONCLUSION Since secondary headache could perfectly mimick primary CH,neuroimaging should be conducted in patients in whom primary and secondary headaches are suspected.Cerebral magnetic resonance imaging scans is the diagnostic management of choice,and further examinations include vessel imaging with contrast agents and dedicated scans focusing on specific cerebral areas(sinuses,ocular and sellar regions).Neuroimaging is as necessary at follow-up visits as at the first observation.

Physiological and pathological insights into exosomes in the brain

Exosomes are small vesicles secreted by all cell types in the brain and play a role in cell-cell communication through the transfer of cargo or encapsulation.Exosomes in the brain have considerable impact on neuronal development,activation,and regeneration.In addition,exosomes are reported to be involved in the onset and propagation of various neurodegenerative diseases.In this review,we discuss the content of exosomes derived from major cell types in the brain,and their function under physiological and pathological conditions.

Inhibition of immune checkpoints prevents injury-induced heterotopic ossification

Heterotopic ossification(HO),true bone formation in soft tissue,is closely associated with abnormal injury/immune responses.We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins(ICs).We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO.The non-specific immune suppressants,Rapamycin and Ebselen,prevented HO providing evidence of the central role of the immune responses.We examined the expression pattern of ICs and found that they are dysregulated in HO lesions.More importantly,loss of function of inhibitory ICs(including PD1,PD-L1,and CD152)markedly inhibited HO,whereas loss of function of stimulatory ICs(including CD40L and OX-40L)facilitated HO.These findings suggest that IC inhibitors may provide a therapeutic approach to prevent or limit the extent of HO.

Imaging presentation of biliary adenofibroma:A case report

BACKGROUND Biliary adenofibroma(BF)is a rare benign epithelial tumor with the possibility of malignant transformation.Its main pathological feature is a well-defined cystic or honeycomb mass.BF has no specific clinical manifestations or laboratory and imaging findings;thus,it is easily misdiagnosed before surgery.This report describes a case in which biliary cystadenoma was misdiagnosed preoperatively and BF was diagnosed postoperatively.The imaging features,particularly the magnetic resonance imaging(MRI)features,were analyzed and summarized.CASE SUMMARY A 68-year-old Chinese man was admitted to our hospital with a 2-mo history of abdominal discomfort.Following admission to our hospital,laboratory examinations showed normal tumor marker concentrations and liver function.Hepatocellular carcinoma was considered after contrast-enhanced ultrasound examination.MRI suggested the possibility of cystadenoma of the bile duct.However,postoperative pathological examination confirmed the diagnosis of BF.No local recurrence was found 1 mo after surgery.CONCLUSION Our objective is to highlight the imaging diagnostic value of BF,especially on an MRI enhanced scan with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid.