The dopaminergic system and Alzheimer's disease

Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

关注免疫检查点抑制剂发生irAE后免疫治疗再挑战

免疫检查点抑制剂(immune-checkpoint inhibitors,ICIs)是近年来肿瘤学领域最重要的突破之一,为不同类型的实体瘤治疗提供了新的范式。ICIs通过阻断免疫内在下调因子,如细胞毒性T淋巴细胞抗原4(CTLA-4)和程序性细胞死亡1(PD-1)或其配体程序性细胞死亡配体1(PD-L1),增加抗肿瘤免疫力[1]。然而,由于免疫应答增强和免疫系统失衡,患者可能会发生免疫相关不良事件(immune-related adverse events,irAE)。

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

Excess cardiovascular mortality in men with non-alcoholic fatty liver disease:A cause for concern!

Non-alcoholic fatty liver disease(NAFLD)has emerged as the commonest cause of chronic liver disease worldwide in recent years.With time,our understanding of NAFLD has evolved from an isolated liver condition to a systemic disease with significant manifestations beyond the liver.Amongst them,cardiovascular diseases(CVDs)are the most important and clinically relevant.Recent research supports a strong independent link between NALFD and CVD beyond the shared risk factors and pathophysiology.Female sex hormones are well known to not only protect against CVD in pre-menopausal females,but also contribute to improved adipose tissue function and preventing its systemic deposition.Recent research highlights the increased risk of major adverse cardiovascular-cerebral events(MACCE)amongst male with NAFLD compared to females.Further,racial variation was observed in MACCE outcomes in NAFLD,with excess mortality in the Native Americans and Asian Pacific Islanders compared to the other races.

Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients:A meta-analysis

BACKGROUND Remimazolam is characterized by rapid action and inactive metabolites.It is used as the general anesthetic for many clinical surgeries.In this study,we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients.AIM To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults.METHODS The PubMed,Web of Science,the Cochrane Library databases were queried for the relevant key words"remimazolam,""and propofol,""and gastrointestinal endoscopy or gastroscopy."The search scope was"Title and Abstract,"and the search was limited to human studies and publications in English.Seven studies wherein remimazolam and propofol were compared were included for the metaanalysis.RESULTS We selected seven randomized controlled trials involving 1445 cases for the analysis.Remimazolam reduced the hypotension(relative risk,RR=0.44,95%CI:0.29-0.66,P=0.000),respiratory depression(RR=0.46,95%CI:0.30-0.70,P=0.000),injection pain(RR=0.12,95%CI:0.05-0.25,P=0.000),bradycardia(RR=0.37,95%CI:0.24-0.58,P=0.000),and time to discharge[weighted mean difference(WMD)=-0.58,95%CI:-0.97 to-0.18,P=0.005],compared to those after propofol administration.No obvious differences were observed for postoperative nausea and vomiting(RR=1.09,95%CI:0.97-1.24,P=0.151),dizziness(RR=0.77,95%CI:0.43-1.36,P=0.361),successful sedation rate(RR=0.96,95%CI:0.93-1.00,P=0.083),or the time to become fully alert(WMD=0.00,95%CI:-1.08-1.08,P=0.998).CONCLUSION Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults.However,further studies are required to confirm these findings.

Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis

BACKGROUND The incidence of chronic kidney disease among patients with diabetes mellitus(DM)remains a global concern.Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus.However,no previous meta-analysis has assessed the effects of body mass index(BMI)on adverse kidney events in patients with DM.AIM To determine the impact of BMI on adverse kidney events in patients with DM.METHODS A systematic literature search was performed on the PubMed,ISI Web of Science,Scopus,Ovid,Google Scholar,EMBASE,and BMJ databases.We included trials with the following characteristics:(1)Type of study:Prospective,retrospective,randomized,and non-randomized in design;(2)participants:Restricted to patients with DM aged≥18 years;(3)intervention:No intervention;and(4)kidney adverse events:Onset of diabetic kidney disease[estimated glomerular filtration rate(eGFR)of<60 mL/min/1.73 m2 and/or microalbuminuria value of≥30 mg/g Cr],serum creatinine increase of more than double the baseline or end-stage renal disease(eGFR<15 mL/min/1.73 m2 or dialysis),or death.RESULTS Overall,11 studies involving 801 patients with DM were included.High BMI(≥25 kg/m2)was significantly associated with higher blood pressure(BP)[systolic BP by 0.20,95%confidence interval(CI):0.15–0.25,P<0.00001;diastolic BP by 0.21 mmHg,95%CI:0.04–0.37,P=0.010],serum albumin,triglycerides[standard mean difference(SMD)=0.35,95%CI:0.29–0.41,P<0.00001],low-density lipoprotein(SMD=0.12,95%CI:0.04–0.20,P=0.030),and lower high-density lipoprotein(SMD=–0.36,95%CI:–0.51 to–0.21,P<0.00001)in patients with DM compared with those with low BMIs(<25 kg/m2).Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI(RR:1.22,95%CI:1.01–1.43,P=0.036).CONCLUSION The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

Efficacy and safety of over-the-scope-clips in the therapy of acute nonvariceal upper gastrointestinal bleeding:Meta-analysis

BACKGROUND Acute nonvariceal upper gastrointestinal bleeding(ANVUGIB)is a frequent lifethreatening acute condition in gastroenterology associated with high morbidity and mortality.Over-the-scope-clip(OTSC)is a new endoscopic hemostasis technique,which is being used in ANVUGIB and is more effective.AIM To summarize and analyze the effects of the OTSC in prevention of recurrent bleeding,clinical success rate,procedure time,hospital stay,and adverse events in the treatment of ANVUGIB,to evaluate whether OTSC can replace standard endoscopic therapy as a new generation of treatment for ANVUGIB.METHODS The literature related to OTSC and standard therapy for ANVUGIB published before January 2023 was searched in PubMed,Web of Science,EMBASE,Cochrane,Google,and CNKI databases.Changes in recurrent bleeding(7 or 30 days),clinical results(clinical success rate,conversion rate to surgery,mortality),therapy time(procedure time,hospital stay),and adverse events in the OTSC intervention group were summarized and analyzed,and the MD or OR of 95%CI is calculated by Review Manager 5.3.RESULTS This meta-analysis involved 11 studies with 1266 patients.Total risk of bias was moderate-to-high.For patients in the OTSC group,7-and 30-days recurrent bleeding rates,as well as procedure time,hospital stay,and intensive care unit stay,were greatly inhibited.OTSC could significantly improve the clinical success rate of ANVUGIB.OTSC therapy did not cause serious adverse and was effective in reducing patient mortality.CONCLUSION OTSC may provide more rapid and sustained hemostasis,and thus,promote recovery and reduce mortality in patients with ANVUGIB.In addition,the safety of OTSC is assured.

Atrial fibrillation and prediabetes:A liaison that merits attention!

Atrial fibrillation(AF)and prediabetes share common pathophysiological mechanisms with endothelial dysfunction and inflammation playing a key role.The resultant vicious cycle which sets in culminates in a higher atherogenicity and thermogenicity of the vascular system resulting in increased major adverse cardiac or cerebrovascular event(MACCE)events.However,the same has not convincingly been verified in real-world settings.In the recent retrospective study by Desai et al amongst AF patients being admitted to hospitals following MACCE,prediabetes emerged as an independent risk factor for MACCE after adjusting for all confounding variables.However,certain questions like the role of metformin,quantifying the risk for MACCE amongst prediabetes compared to diabetes,the positive impact of reversion to normoglycemia remain unanswered.We provide our insights and give future directions for dedicated research in this area to clarify the exact relationship between the two.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excellent model calibration with a score of 0.07.Furthermore,SHAP values highlighted the significance of certain variables in predicting postoperative MACE,with negative noninvasive cardiac stress testing,use of nonselective beta-blockers,direct bilirubin levels,blood type O,and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level.These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE,making it a valuable tool for clinical practice.CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE,using both cardiovascular and hepatic variables.The model demonstrated impressive performance,aligning with literature findings,and exhibited excellent calibration.Notably,our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data,reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

Advances in the study of waterlogging tolerance in plants

Waterlogging is one of the major abiotic stresses threatening crop yields globally.Under waterlogging stress,plants suffer from oxidative stress,heavy metal toxicity and energy deficiency,leading to metabolic disorders and growth inhibition.On the other hand,plants have evolved waterlogging-tolerance or adaptive mechanisms,including morphological changes,alternation of respiratory pathways,antioxidant protection and endogenous hormonal regulation.In this review,recent advances in studies on the effects of waterlogging stress and the mechanisms of waterlogging tolerance in plants are presented,and the genetic differences in waterlogging tolerance among plant species or genotypes within a species are illustrated.We also summarize the identified QTLs and key genes associated with waterlogging tolerance.

Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Adverse drug reactions of first-line antitubercular drugs:A retrospective study on characteristics,management,factors,and impacts

Objective:To elucidate the characteristics,management strategies,risk factors,and clinical impacts associated with adverse drug reactions(ADRs)induced by first-line antitubercular drugs to enhance tuberculosis(TB)management.Methods:A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak,Malaysia.Only the initial TB treatment and occurrence of specific ADRs within the study period were considered.Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs.Results:Among 2953 cases,705(23.9%)developed ADRs.Cutaneous reactions were the most prevalent(47.1%),followed by hepatotoxicity(32.8%)and gastrointestinal disturbances(29.8%).Six out of seven types of ADRs investigated occurred within the intensive phase,mostly manifesting at approximately 2 weeks of initiation.Hepatotoxicity resulted in the majority(85.3%)of treatment discontinuations,while vision problems led to treatment modifications in half of the cases.Risk factors for all ADRs included age≥60 years,females,illicit drug use,and comorbidities such as HIV-positive,diabetes,and chronic liver disease.Alcohol consumption was independently associated with hepatotoxicity.ADRs caused around one-third of interruptions exceeding 2 weeks(33.0%)and subsequently necessitated treatment restarts(34.5%).Conclusions:Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment.Close ADR monitoring and reporting are essential to strengthen ADR management.

Efficacy and safety of low-dose tetracycline,amoxicillin quadruple therapy in Helicobacter pylori infection:A retrospective single center study

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have declined with the rise of antibiotic-resistant strains in recent years.Although highly effective with a low prevalence of resistance,standard dose tetracycline is associated with frequent adverse events.The efficacy and safety of low-dose tetracycline as part of tetra-cycline and amoxicillin-containing bismuth quadruple therapy are not well described.AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients with H.pylori infection receiving tetracycline,amoxicillin,proton pump inhibitor,and bismuth for 14 days at Sir Run Run Shaw Hospital(1/2022-6/2023)were evaluated.The low-dose tetracycline group received tetracycline 500 mg twice daily(bid)while the standard dose group received 750 mg bid or 500 mg three times daily(tid).Primary endpoints were H.pylori eradication rate and treatment-related adverse events.

Predictors of Adverse Pregnancy Outcomes Following Traumatic Injuries

Objective After traumatic injury in pregnant women,providing timely and appropriate management for high-risk patients is crucial for both pregnant women and fetuses.This study aimed to identify risk factors that predict adverse pregnancy outcomes after traumatic injury.Methods A retrospective cohort study including 317 pregnant patients who experienced trauma was conducted.The collected data included general demographics,injury mechanisms and adverse pregnancy outcomes.Patients were divided into two subgroups based on the absence or presence of trauma-related adverse pregnancy outcomes.Univariate and multivariate logistic regressions were conducted to estimate the associations between clinical variables and adverse pregnancy outcomes.Results A total of 41(12.93%)patients experienced adverse pregnancy outcomes within the first 24 h post-trauma.This study revealed that age>35 years(OR=14.995,95%CI:5.024–44.755,P<0.001),third trimester trauma(OR=3.878,95%CI:1.343–11.204,P=0.012),abdominal pain(OR=3.032,95%CI:1.221–7.527,P=0.017),vaginal bleeding(OR=3.226,95%CI:1.093–9.523,P=0.034),positive scan in focused assessment with sonography for trauma(FAST)positive(OR=8.496,95%CI:2.825–25.555,P<0.001),9≤injury severity score(ISS)<16(OR=3.039,95%CI:1.046–8.835,P=0.041)and ISS≥16(OR=5.553,95%CI:1.387–22.225,P=0.015)increased the probability of posttraumatic adverse pregnancy outcomes.Maternal age,gestational age at delivery,vaginal bleeding and positive FAST results were risk factors for abnormal delivery.Conclusion Advanced maternal age,third trimester,and positive FAST results should alert multidisciplinary trauma teams to closely monitor patients to prevent adverse pregnancy outcomes.

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa.First,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression.In particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer

In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite instability(MSI)in gastric cancer(GC).The four pillars of GC management have long been considered,including surgery,chemotherapy,radiotherapy and targeted therapy.However,immunotherapy has recently emerged as a“fifth pillar”,and its use is rapidly expanding.There are four principal strategies for tumor immunotherapy:ICIs,tumor vaccines,adoptive immunotherapy and nonspecific immunomodulators.Of them,ICIs are the most advanced and widespread type of cancer immunotherapy for GC.Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy.In particular,inhibition of the PD-1/PD-L1 axis with ICIs,including nivolumab and pembrolizumab,has emerged as a novel treatment strategy for advanced GC.Unfortunately,these therapies are sometimes associated with often subtle,potentially fatal immune-related adverse events(irAEs),including dermatitis,diarrhea,colitis,endocrinopathy,hepatotoxicity,neuropathy and pneumonitis.We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges,emergency department revisits,and downstream complications.Recent studies have revealed that MSI-high or mismatch-repair-deficient tumors,regardless of their primary site,have a promising response to ICIs.So,it is important to detect MSI before applying ICIs for treatment of GC.

ED-Ged:Nighttime Image Semantic Segmentation Based on Enhanced Detail and Bidirectional Guidance

Semantic segmentation of driving scene images is crucial for autonomous driving.While deep learning technology has significantly improved daytime image semantic segmentation,nighttime images pose challenges due to factors like poor lighting and overexposure,making it difficult to recognize small objects.To address this,we propose an Image Adaptive Enhancement(IAEN)module comprising a parameter predictor(Edip),multiple image processing filters(Mdif),and a Detail Processing Module(DPM).Edip combines image processing filters to predict parameters like exposure and hue,optimizing image quality.We adopt a novel image encoder to enhance parameter prediction accuracy by enabling Edip to handle features at different scales.DPM strengthens overlooked image details,extending the IAEN module’s functionality.After the segmentation network,we integrate a Depth Guided Filter(DGF)to refine segmentation outputs.The entire network is trained end-to-end,with segmentation results guiding parameter prediction optimization,promoting self-learning and network improvement.This lightweight and efficient network architecture is particularly suitable for addressing challenges in nighttime image segmentation.Extensive experiments validate significant performance improvements of our approach on the ACDC-night and Nightcity datasets.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.