Biliary atresia is a progressive disease involving the intrahepatic and extrahepatic bile ducts. At present, the widely used treatment strategy is portojejunostomy (Kasai procedure). However, fat-soluble vitamin deficiency is common in children with biliary atresia, leading to growth retardation and malnutrition, which further affects the therapeutic effect prognosis of children. This article reviews the etiology, performance, prevention and treatment of fat-soluble vitamins deficiency in children with biliary atresia.

Objective To investigate the prognostic value of the platelet-to-lymphocyte ratio(PLR)at different early time points in adult patients undergoing veno-arterial extracorporeal membrane oxygenation(VA-ECMO).Methods A retrospective study was conducted,selecting 55 adult patients who underwent VA-ECMO treatment at the First Hospital of Jiaxing from June 2020 to October 2022 as the study subjects.Then,the patients'gender,age,past history[including hypertension,diabetes,heart disease,chronic obstructive pulmonary disease(COPD)],and the reason for extracorporeal membrane pulmonary oxygenation(ECMO)adjuvant therapy[including severe myocarditis,acute myocardia infarction,in-hospital and out-of-hospital cardiac arrest,severe closed craniocerebral injury,severe pneumonia,pelvic fracture,other(pulmonary embolism,electrocution,traumatic hepatic rupture,post-partum hemorrhage,severe acute pancreatitis,crush syndrome)],acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)at the time of admission,and ECMO peripheral blood tests[creatinine,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood lactate acid(Lac),white blood cell count(WBC),neutrophil count(NEU),lymphocyte count(LYM),hemoglobin(Hb),and platelet count(PLT)]and the last time prior to ECMO assistance,24 hours prior to the occurrence of acute kidney injury(AKI),and 24 hours after the occurrence of AKI.PLR levels at 24 hours ECMO,and the proportion of continuous renal replacement therapy(CRRT).The patients were divided into a death group and a survival group based on their 30-day prognosis and further categorized into a CRRT group and a non-CRRT group based on whether CRRT was administered.Clinical indicators of patients with different prognosis and the differences in PLR levels between CRRT and non-CRRT groups were compared.Logistic regression analysis was used to identify independent risk factors affecting the 30-day prognosis of VA-ECMO patients.The receiver operator characteristic(ROC curves)were plotted to evaluate the prognostic predictive value of each risk factor.Results Compared to the survival group,the death group had significantly higher APACHEⅡscores,SOFA scores,LYM and proportion receiving CRRT[APACHEⅡscore:34.00(28.50,36.00)vs.25.00(14.75,34.00),SOFA score:5.00(4.00,6.50)vs.3.00(2.00,5.25),LYM(×109/L):3.40±1.97 vs.2.24±2.11,proportion receiving CRRT:91.30%(21/23)vs.62.50%(20/32)],and a significantly lower level of the last PLR prior to ECMO adjuvant[30.00(21.06,48.17)vs.58.82(41.80,145.72)],and the differences were statistically significant(all P<0.05).Logistic regression analysis showed that the levels of the last PLR before ECMO assistance[odds ratio(OR)=0.965,95%confidence interval(95%CI)was 0.938-0.993,P=0.013],APACHEⅡscore at the time of admission(OR=1.121,95%CI was 1.018-1.234,P=0.020),and CRRT(OR=7.734,95%CI was 1.042-57.401,P=0.045)were independent risk factors affecting the prognosis of the VA-ECMO patients at 30 days after adjuvant;the ROC curve analysis showed that APACHEⅡscore,CRRT and the last PLR level before ECMO assistance had a predictive value for the prognosis of VA-ECMO patients 30 days after assistance,in which the APACHEⅡscore+the last PLR level before ECMO assistance had the greatest predictive value in predicting the prognosis of the patients,with area under the curve(AUC)of 0.846,with a sensitivity of 62.5%and a specificity of 95.7%.Higher early PLR levels were associated with better prognosis.In the CRRT group,PLR levels at 24 hours before ECMO initiation,24 hours before AKI onset,and 24 hours after AKI onset were significantly lower than those in the non-CRRT group(all P<0.05).Conclusion Early PLR levels and CRRT administration have significant predictive value for the prognosis of patients undergoing VA-ECMO therapy.

Age-related macular degeneration(AMD)is one of the leading causes of blindness in the elderly.Wet AMD(nAMD)accounts for more than 90％of AMD-related vision loss.Pathologically,nAMD is defined by choroidal neovascu-larization(CNV)and chronic retinal inflammation driven by oxidative stress,complement activation,pro-inflammatory cy-tokines,and overexpression of vascular endothelial growth factor(VEGF).Yet anti-VEGF monotherapy often falls short.The nuclear factor kappa-B(NF-κB)signaling cascade,acting through both canonical and non-canonical pathways,or-chestrates the expression of genes governing immunity,inflammation,apoptosis,and angiogenesis.In nAMD,oxidative stress and complement fragments ignite NF-κB,unleashing a repertoire of pro-inflammatory and pro-angiogenic mediators that fuel CNV.Pharmacologic or genetic suppression of NF-κB dampens both inflammation and neovascularization,attenua-ting experimental CNV.Thus,dissecting the molecular machinery of NF-κB signaling in nAMD may uncover novel combina-tion strategies that enhance therapeutic efficacy and curb anti-VEGF resistance.

Objective To investigate the prognostic value of the platelet-to-lymphocyte ratio(PLR)at different early time points in adult patients undergoing veno-arterial extracorporeal membrane oxygenation(VA-ECMO).Methods A retrospective study was conducted,selecting 55 adult patients who underwent VA-ECMO treatment at the First Hospital of Jiaxing from June 2020 to October 2022 as the study subjects.Then,the patients'gender,age,past history[including hypertension,diabetes,heart disease,chronic obstructive pulmonary disease(COPD)],and the reason for extracorporeal membrane pulmonary oxygenation(ECMO)adjuvant therapy[including severe myocarditis,acute myocardia infarction,in-hospital and out-of-hospital cardiac arrest,severe closed craniocerebral injury,severe pneumonia,pelvic fracture,other(pulmonary embolism,electrocution,traumatic hepatic rupture,post-partum hemorrhage,severe acute pancreatitis,crush syndrome)],acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)at the time of admission,and ECMO peripheral blood tests[creatinine,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood lactate acid(Lac),white blood cell count(WBC),neutrophil count(NEU),lymphocyte count(LYM),hemoglobin(Hb),and platelet count(PLT)]and the last time prior to ECMO assistance,24 hours prior to the occurrence of acute kidney injury(AKI),and 24 hours after the occurrence of AKI.PLR levels at 24 hours ECMO,and the proportion of continuous renal replacement therapy(CRRT).The patients were divided into a death group and a survival group based on their 30-day prognosis and further categorized into a CRRT group and a non-CRRT group based on whether CRRT was administered.Clinical indicators of patients with different prognosis and the differences in PLR levels between CRRT and non-CRRT groups were compared.Logistic regression analysis was used to identify independent risk factors affecting the 30-day prognosis of VA-ECMO patients.The receiver operator characteristic(ROC curves)were plotted to evaluate the prognostic predictive value of each risk factor.Results Compared to the survival group,the death group had significantly higher APACHEⅡscores,SOFA scores,LYM and proportion receiving CRRT[APACHEⅡscore:34.00(28.50,36.00)vs.25.00(14.75,34.00),SOFA score:5.00(4.00,6.50)vs.3.00(2.00,5.25),LYM(×109/L):3.40±1.97 vs.2.24±2.11,proportion receiving CRRT:91.30%(21/23)vs.62.50%(20/32)],and a significantly lower level of the last PLR prior to ECMO adjuvant[30.00(21.06,48.17)vs.58.82(41.80,145.72)],and the differences were statistically significant(all P<0.05).Logistic regression analysis showed that the levels of the last PLR before ECMO assistance[odds ratio(OR)=0.965,95%confidence interval(95%CI)was 0.938-0.993,P=0.013],APACHEⅡscore at the time of admission(OR=1.121,95%CI was 1.018-1.234,P=0.020),and CRRT(OR=7.734,95%CI was 1.042-57.401,P=0.045)were independent risk factors affecting the prognosis of the VA-ECMO patients at 30 days after adjuvant;the ROC curve analysis showed that APACHEⅡscore,CRRT and the last PLR level before ECMO assistance had a predictive value for the prognosis of VA-ECMO patients 30 days after assistance,in which the APACHEⅡscore+the last PLR level before ECMO assistance had the greatest predictive value in predicting the prognosis of the patients,with area under the curve(AUC)of 0.846,with a sensitivity of 62.5%and a specificity of 95.7%.Higher early PLR levels were associated with better prognosis.In the CRRT group,PLR levels at 24 hours before ECMO initiation,24 hours before AKI onset,and 24 hours after AKI onset were significantly lower than those in the non-CRRT group(all P<0.05).Conclusion Early PLR levels and CRRT administration have significant predictive value for the prognosis of patients undergoing VA-ECMO therapy.

Age-related macular degeneration(AMD)is one of the leading causes of blindness in the elderly.Wet AMD(nAMD)accounts for more than 90％of AMD-related vision loss.Pathologically,nAMD is defined by choroidal neovascu-larization(CNV)and chronic retinal inflammation driven by oxidative stress,complement activation,pro-inflammatory cy-tokines,and overexpression of vascular endothelial growth factor(VEGF).Yet anti-VEGF monotherapy often falls short.The nuclear factor kappa-B(NF-κB)signaling cascade,acting through both canonical and non-canonical pathways,or-chestrates the expression of genes governing immunity,inflammation,apoptosis,and angiogenesis.In nAMD,oxidative stress and complement fragments ignite NF-κB,unleashing a repertoire of pro-inflammatory and pro-angiogenic mediators that fuel CNV.Pharmacologic or genetic suppression of NF-κB dampens both inflammation and neovascularization,attenua-ting experimental CNV.Thus,dissecting the molecular machinery of NF-κB signaling in nAMD may uncover novel combina-tion strategies that enhance therapeutic efficacy and curb anti-VEGF resistance.

Biliary atresia is a progressive disease involving the intrahepatic and extrahepatic bile ducts. At present, the widely used treatment strategy is portojejunostomy (Kasai procedure). However, fat-soluble vitamin deficiency is common in children with biliary atresia, leading to growth retardation and malnutrition, which further affects the therapeutic effect prognosis of children. This article reviews the etiology, performance, prevention and treatment of fat-soluble vitamins deficiency in children with biliary atresia.

Acute ischemic stroke(AIS)is associated with a high mortality and disability rate.Endovascular therapy(EVT)has emerged as a primary treatment method for achieving vascular reperfusion in large vessel occlusion AIS patients.The cerebral hemodynamic status of patients undergoing reperfusion therapy is closely linked to the extent of cerebral vascular reperfusion and improvement in the ischemic penumbra at the site of injury.Transcranial Doppler(TCD)ultrasound offers non-invasive,reliable,and convenient advantages for evaluating intracranial vessel occlusion or stenosis,guiding treatment decisions,and predicting patient outcomes.The authors reviewed the application progress of TCD in AIS patients.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

Dysbiosis can cause microenvironmental dysregulation, which can further lead to local or systemic diseases, such as caries, inflammatory bowel disease, obesity, and diabetes. Dysbiosis is primarily manifested as the disturbance of metabolic processes and products. Arginine plays an important role in various metabolic processes and homeostasis of the microbial flora and the host. This study aims to explore the potential therapeutic value of arginine and its metabolism and homeostasis regulation in diseases associated with oral-intestinal dysbiosis. Host and microbial homeostasis can be restored by regulating the composition or function of host microbiota, and arginine has been found to exhibit significant clinical potential in restoring host microbiota composition and function. For example, arginine can reduce the risk of caries by regulating the relative abundance of Streptococcus mutans and Streptococcus sanguineus. Additionally, arginine metabolism may play a therapeutic role in inflammatory bowel disease and obesity by regulating the relative abundance of Firmicutes and Bacteroidetes. In addition, supplementation of arginine and its metabolite polyamine has clinical prospects in the treatment of diabetic patients with ketoacidosis. Although studies have demonstrated the therapeutic role of arginine in oral, intestinal, and metabolism-related diseases, the specific mechanism is yet to be explored. In addition, further research is required to determine the optimal clinical dosage of arginine that can maintain microbiota homeostasis without causing any side effects.

BACKGROUND:Pretreatment with moxibustion is a preventive treatment in traditional Chinese medicine.Pretreatment with moxibustion at the onset of prodromal symptoms can significantly reduce the symptoms and delay the onset of many diseases,but the exact mechanism remains to be studied. OBJECTIVE:To investigate the mechanism of SIRT1/FoxO3 pathway in moxibustion pretreatment to ameliorate oxidative stress injury in cerebral ischemia-reperfusion model rats. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham-operated group,model group,moxibustion pretreatment group,and moxibustion pretreatment+EX527(SIRT1 inhibitor)group,with 12 rats in each group.The moxibustion pretreatment group was given moxibustion with seed-sized moxa cone at Baihui,Dazhui,and Zusanli before modeling,three moxa-cones per acupoint,once a day for 7 days.In the model group,moxibustion pretreatment group and moxibustion pretreatment+EX527 group,the rat model of middle cerebral artery occlusion was made by suturing of the middle cerebral artery 30 minutes after the last moxibustion.After 2 hours of cerebral ischemia,the middle artery suture was removed and the rats were reperfused for 12 hours.In the sham-operated group,only the common carotid artery,internal carotid artery,and external carotid artery were dissected without suturing the middle cerebral artery.In the moxibustion pretreatment+EX527 group,EX527(15 mg/kg)was given intraperitoneally 30 minutes before each moxibustion.After 12 hours of reperfusion,the rats were scored for neurological deficits,and the cerebral infarct volume was calculated by 2,3,5-triphenyltetrazolium chloride staining method.The levels of oxidative stress factors in the infarcted tissues were detected by the kit method,and western-blot method was used to detect the expression levels of SIRT1,FoxO3,p-FoxO3 and brain-derived neurotrophic factor in the ischemic area of the cerebral cortex. RESULTS AND CONCLUSION:After 12 hours of reperfusion,the neurobehavioral score in the model group was significantly higher than that in the sham-operated group(P＜0.01),while the score in the moxibustion pretreatment group was significantly lower than that in the model group(P＜0.01)and moxibustion pretreatment+EX527 group(P＜0.05).There were no obvious infarct foci in the brain tissue of the sham-operated rats,but obvious ischemic foci were observed in the right side of the brain tissue of the rats in the model group(P＜0.01).The right infarct volume in the moxibustion pretreatment group was significantly reduced compared with the model group(P＜0.01),while the right infarct volume in the moxibustion pretreatment+EX527 group was significantly enlarged compared with the moxibustion pretreatment group.After 12 hours of reperfusion,the level of malondialdehyde was significantly elevated(P＜0.01)and the expression of superoxide dismutase was significantly decreased(P＜0.01)in the model group compared with the sham-operated group.The levels of malondialdehyde was significantly decreased(P＜0.01,P＜0.05)and the expression of superoxide dismutase was significantly increased(P＜0.01,P＜0.05)in the moxibustion pretreatment group compared with the model group and the moxibustion pretreatment+EX527 group.Western blot results showed that the expression levels of SIRT1,FoxO3,p-FoxO3,and brain-derived neurotrophic factor proteins were significantly higher in the model group compared with the sham-operated group(P＜0.01);compared with the model group,the expression levels of SIRT1,FoxO3,and brain-derived neurotrophic factor were significantly higher in the moxibustion pretreatment group(P＜0.01),and p-FoxO3 expression was significantly lower(P＜0.01);compared with the moxibustion pretreatment+EX527 group,the expression levels of SIRT1,FoxO3,and brain-derived neurotrophic factor were elevated in the moxibustion pretreatment group(P＜0.05),and no statistically significant difference was found in the p-FoxO3 expression(P＞0.05).To conclude,moxibustion pretreatment can significantly improve neurological function in rats after cerebral ischemia-reperfusion,and the mechanism may be related to the activation of SIRT1/FoxO3 pathway to reduce oxidative stress injury in the rat model of cerebral ischemia-reperfusion.