Liver is a vital organ in the human body and plays a central role in the metabolism and detoxification of endotoxins and exotoxins.Bilirubin is an endotoxin derived from hemoglobin(Hb).Removing excess bilirubin in the...Liver is a vital organ in the human body and plays a central role in the metabolism and detoxification of endotoxins and exotoxins.Bilirubin is an endotoxin derived from hemoglobin(Hb).Removing excess bilirubin in the blood is crucial for the treatment of liver diseases.Hemoperfusion,which relies on adsorbents to efficiently adsorb toxins,is a widely applied procedure for the removal of blood toxins.To broaden and improve the range and performance of hemoperfusion adsorbents,we synthesized cationic hyper crosslinked polymers(HCPs)with strong affinity for bilirubin.This material exhibited outstanding adsorption performance,with a maximum adsorption capacity of 934 mg/g and a removal efficiency of 96%.Further investigation confirmed their excellent selectivity,reusability,and biocompatibility.These findings expand the potential applications of HCPs and provide insight into strategies for constructing promising hemoperfusion adsorbent materials.展开更多
BACKGROUND Gastric cancer is the most common malignancy of the digestive system and surgical resection is the primary treatment.Advances in surgical technology have reduced the risk of complications after radical gast...BACKGROUND Gastric cancer is the most common malignancy of the digestive system and surgical resection is the primary treatment.Advances in surgical technology have reduced the risk of complications after radical gastrectomy;however,post-surgical pancreatic fistula remain a serious issue.These fistulas can lead to abdominal infections,anastomotic leakage,increased costs,and pain;thus,early diagnosis and prevention are crucial for a better prognosis.Currently,C-reactive protein(CRP),procalcitonin(PCT),and total bilirubin(TBil)levels are used to predict post-operative infections and anastomotic leakage.However,their predictive value for pancreatic fistula after radical gastrectomy for gastric cancer remains unclear.The present study was conducted to determine their predictive value.AIM To determine the predictive value of CRP,PCT,and TBil levels for pancreatic fistula after gastric cancer surgery.METHODS In total,158 patients who underwent radical gastrectomy for gastric cancer at our hospital between January 2019 and January 2023 were included.The patients were assigned to a pancreatic fistula group or a non-pancreatic fistula group.Multivariate logistic analysis was conducted to assess the factors influencing development of a fistula.Receiver operating characteristic(ROC)curves were used to determine the predictive value of serum CRP,PCT,and TBil levels on day 1 postsurgery.RESULTS On day 1 post-surgery,the CRP,PCT,and TBil levels were significantly higher in the pancreatic fistula group than in the non-pancreatic fistula group(P<0.05).A higher fistula grade was associated with higher levels of the indices.Univariate analysis revealed significant differences in the presence of diabetes,hyperlipidemia,pancreatic injury,splenectomy,and the biomarker levels(P<0.05).Logistic multivariate analysis identified diabetes,hyperlipidemia,pancreatic injury,CRP level,and PCT level as independent risk factors.ROC curves yielded predictive values for CRP,PCT,and TBil levels,with the PCT level having the highest area under the curve(AUC)of 0.80[95%confidence interval(CI):0.72-0.90].Combined indicators improved the predictive value,with an AUC of 0.86(95%CI:0.78-0.93).CONCLUSION Elevated CRP,PCT,and TBil levels predict risk of pancreatic fistula post-gastrectomy for gastric cancer.展开更多
Jaundice,common condition in newborns,is characterized by yellowing of the skin and eyes due to elevated levels of bilirubin in the blood.Timely detection and management of jaundice are crucial to prevent potential co...Jaundice,common condition in newborns,is characterized by yellowing of the skin and eyes due to elevated levels of bilirubin in the blood.Timely detection and management of jaundice are crucial to prevent potential complications.Traditional jaundice assessment methods rely on visual inspection or invasive blood tests that are subjective and painful for infants,respectively.Although several automated methods for jaundice detection have been developed during the past few years,a limited number of reviews consolidating these developments have been presented till date,making it essential to systematically evaluate and present the existing advancements.This paper fills this gap by providing a thorough survey of automated methods for jaundice detection in neonates.The primary focus of the survey is to review the existing methodologies,techniques,and technologies used for neonatal jaundice detection.The key findings from the review indicate that image-based bilirubinometers and transcutaneous bilirubinometers are promising non-invasive alternatives,and provide a good trade-off between accuracy and ease of use.However,their effectiveness varies with factors like skin pigmentation,gestational age,and measurement site.Spectroscopic and biosensor-based techniques show high sensitivity but need further clinical validation.Despite advancements,several challenges including device calibration,large-scale validation,and regulatory barriers still haunt the researchers.Standardization,regulatory compliances,and seamless integration into healthcare workflows are the key hurdles to be addressed.By consolidating the current knowledge and discussing the challenges and opportunities in this field,this survey aims to contribute to the advancement of automatic jaundice detection and ultimately improve neonatal care.展开更多
BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,an...BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.展开更多
Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those inv...Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those involving hemolysis or impaired erythropoiesis,may play a significant role in the formation of gallblad-der stones,predominantly pigment stones.This review explores the pathophysio-logical mechanisms linking hematological disorders,such as hemolytic anemias,myeloproliferative disorders,and hematological malignancies,with gallbladder stone development.We also examine the influence of treatments for hemato-logical conditions,such as blood transfusions and chemotherapy,on gallstone risk.Additionally,this article discusses the clinical implications of gallbladder stones in patients with hematological disorders,including diagnostic challenges,management strategies,and surgical considerations.By providing a compre-hensive overview of current knowledge,this review aims to highlight the need for further research into the interplay between hematological disorders and gall-bladder stones,potentially improving preventive and therapeutic strategies in these patient populations.展开更多
Hereditary spherocytosis(HS),a common inherited hemolytic anemia,is characterized by red blood cell membrane protein defects leading to chronic hemolysis.This condition significantly predisposes patients to gallstone ...Hereditary spherocytosis(HS),a common inherited hemolytic anemia,is characterized by red blood cell membrane protein defects leading to chronic hemolysis.This condition significantly predisposes patients to gallstone disease,including both gallbladder and bile duct stones,due to excessive bilirubin production from hemolysis.Gallstones in HS patients,primarily composed of bilirubin,can lead to complications such as cholecystitis,cholangitis,and obstructive jaundice.This review provides a comprehensive landscape of the pathophysiological mechanisms linking HS to gallstone formation,emphasizing the roles of hemolysis,bile composition,and genetic factors.It also discusses the clinical manifestations of gallstone disease in HS,including recurrent jaundice and biliary obstruction,and highlights the diagnostic value of imaging modalities such as ultrasonography and magnetic resonance cholangiopancreatography.Furthermore,current management strategies,including splenectomy,cholecystectomy,and endoscopic approaches for bile duct stones,are examined in the context of HS.By synthesizing existing knowledge,this review aims to provide insights into improving the diagnosis,prevention,and treatment of gallstone disease in patients with HS,while identifying gaps for future research.展开更多
BACKGROUND Diabetic retinopathy(DR)is a major cause of visual impairment and blindness.However,the current DR biomarkers are insufficient for accurately predicting its onset.AIM To identify a novel marker for predicti...BACKGROUND Diabetic retinopathy(DR)is a major cause of visual impairment and blindness.However,the current DR biomarkers are insufficient for accurately predicting its onset.AIM To identify a novel marker for predicting the risk of developing DR in patients with type 2 diabetes mellitus(T2DM).METHODS We conducted a cross-sectional study involving 6993 hospitalized T2DM patients between 2013 and 2020.Patients were divided into two groups:The DR group and the non-DR group.Data were analyzed using univariate,correlation,multivariate,subgroup,and receiver operating characteristic curve analyses.RESULTS Total bilirubin,indirect bilirubin(IBIL),and direct bilirubin were negatively correlated with the risk of developing DR(P<0.001).Moreover,these three factors were all positively correlated with clinical indicators related to DR,including the estimated glomerular filtration rate,the albumin/creatinine ratio,and the 1,25-dihydroxyvitamin D3 level(P<0.001).After adjusting for multiple variables,greater IBIL levels remained independently associated with a lower risk of developing DR(odds ratio=0.500;95%confidence interval:0.363-0.686;P<0.001).The optimal IBIL cutoff point for predicting the risk of DR in male patients with elevated diastolic blood pressure was 0.655μmol/dL(area under the curve=0.662).CONCLUSION These findings suggest that IBIL could be a valuable biomarker for predicting DR risk,offering a noninvasive,cost-effective,and readily available clinical tool for the early identification of high-risk patients.Future multicenter and longitudinal studies are warranted to validate these findings and further explore the biological mechanisms underlying the protective role of IBIL in DR.展开更多
BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle fact...BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle factors,and diseases.Obstructive jaundice is one of the most common pathophysiological changes in patients needing hepatobiliary or pancreatic operations that can adversely affect the tissue and organ function throughout the human body.However,the effects of obstructive jaundice on the occurrence of sarcopenia remain unclear.AIM To investigate the incidence of sarcopenia in patients with surgical obstructive jaundice and the association of sarcopenia with postoperative outcome.METHODS This cross-sectional study was conducted from December 2019 to January 2024.Data retrieved included patient demographics,disease entities,sarcopenia-related parameters(including grip strength,6-m walking time,and limb skeletal muscle mass index),postoperative complications,and length of hospital stay.Sarcopenia was confirmed using Asian Working Group standards.Logistic regression was used to analyze the relationship between total bilirubin level and sarcopenia.The factors influencing sarcopenia in patients with surgical obstructive jaundice and association of sarcopenia with postoperative complications were also investigated.RESULTS Overall,1708 patients met the inclusion criteria,with a mean age of 60.09±13.52 years(sex:52.28%male).There were 383 patients(22.42%)with obstructive jaundice and 1325(77.58%)without jaundice.Sarcopenia,low walking speed,low grip strength,and low limb skeletal muscle index were more prevalent in patients with obstructive jaundice than nonobstructive jaundice.The odds ratio(OR)for sarcopenia in patients with obstructive jaundice was 1.689[95%confidence interval(CI):1.295-2.203,P<0.001],indicating that jaundice is a significant risk factor for sarcopenia.The occurrence of sarcopenia was higher in patients with severe obstructive jaundice than mild obstructive jaundice(39.3%vs 22.8%,P<0.05).Obstructive jaundice was positively correlated with reduced walking speed(OR=1.627,95%CI:1.185-2.234,P=0.003)and decreased grip strength(OR=1.669,95%CI:1.212-2.300,P=0.002).Age(OR=1.077,95%CI:1.040-1.114,P<0.001)and body mass index(OR=0.703,95%CI:0.630-0.784,P<0.001)were independent risk factors of sarcopenia in patients with obstructive jaundice.Patients with obstructive jaundice and sarcopenia had a higher rate of postoperative complications(46.3%vs 33.1%,P=0.032),longer postoperative hospital stays(11.33±6.75 days vs 9.19±7.32 days,P=0.016),and longer total hospital stays(17.10±7.69 days vs 15.98±8.55 days,P=0.032)than those without sarcopenia.CONCLUSION Sarcopenia is more prevalent in patients with obstructive jaundice and is positively correlated with the degree of jaundice.Sarcopenia prolongs hospital stays and is associate with postoperative complications.展开更多
Acute Bilirubin Encephalopathy(ABE)is a significant threat to neonates and it leads to disability and high mortality rates.Detecting and treating ABE promptly is important to prevent further complications and long-ter...Acute Bilirubin Encephalopathy(ABE)is a significant threat to neonates and it leads to disability and high mortality rates.Detecting and treating ABE promptly is important to prevent further complications and long-term issues.Recent studies have explored ABE diagnosis.However,they often face limitations in classification due to reliance on a single modality of Magnetic Resonance Imaging(MRI).To tackle this problem,the authors propose a Tri-M2MT model for precise ABE detection by using tri-modality MRI scans.The scans include T1-weighted imaging(T1WI),T2-weighted imaging(T2WI),and apparent diffusion coefficient maps to get indepth information.Initially,the tri-modality MRI scans are collected and preprocessesed by using an Advanced Gaussian Filter for noise reduction and Z-score normalisation for data standardisation.An Advanced Capsule Network was utilised to extract relevant features by using Snake Optimization Algorithm to select optimal features based on feature correlation with the aim of minimising complexity and enhancing detection accuracy.Furthermore,a multi-transformer approach was used for feature fusion and identify feature correlations effectively.Finally,accurate ABE diagnosis is achieved through the utilisation of a SoftMax layer.The performance of the proposed Tri-M2MT model is evaluated across various metrics,including accuracy,specificity,sensitivity,F1-score,and ROC curve analysis,and the proposed methodology provides better performance compared to existing methodologies.展开更多
Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, o...Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, ox and common carp biles approximately in the Zhou dynasty (c. 1046-256 BCE). Overall, different animal biles were prescribed principally for the treatment of liver, biliary, skin (including burns), gynecological and heart diseases, as well as diseases of the eyes, ears, nose, mouth and throat. We present an informed opinion of the clinical efficacy of the medicinal uses of the different animal biles based on their presently known principal chemical components which are mostly steroidal detergent-like molecules and the membrane lipids such as unesterified cholesterol and mixed phosphatidylcholines and sometimes sphingomyelin, as well as containing lipopigments derived from heme principally bilirubin glucuronides. All of the available information on the ethnopharmacological uses of biles in TCM were collated from the rich collection of ancient Chinese books on materia medica held in libraries in China and United States and the composition of various animal biles was based on rigorous separatory and advanced chemical identification techniques published since the mid-20<sup>th</sup> century collected via library (Harvard’s Countway Library) and electronic searches (PubMed and Google Scholar). Our analysis of ethnomedical data and information on biliary chemistry shows that specific bile salts, as well as the common bile pigment bilirubin and its glucuronides plus the minor components of bile such as vitamins A, D, E, K, as well as melatonin (N-acetyl-5-methoxytryptamine) are salutary in improving liver function, dissolving gallstones, inhibiting bacterial and viral multiplication, promoting cardiac chronotropsim, as well as exhibiting anti-inflammatory, anti-pyretic, anti-oxidant, sedative, anti-convulsive, anti-allergic, anti-congestive, anti-diabetic and anti-spasmodic effects. Pig, wild boar and human biles diluted with alcohol were shown to form an artificial skin for burns and wounds one thousand years ago in the Tang dynasty (618-907 CE). Although various animal biles exhibit several generic effects in common, a number of biles appear to be advantageous for specific therapeutic indications. We attempt to understand these effects based on the pharmacology of individual components of bile as well as attempting to identify a variety of future research needs.展开更多
BACKGROUND Unconjugated bilirubin(UCB)is generally considered toxic but has gained recent prominence for its anti-inflammatory properties.However,the effects of it on the interaction between intestinal flora and organ...BACKGROUND Unconjugated bilirubin(UCB)is generally considered toxic but has gained recent prominence for its anti-inflammatory properties.However,the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved.AIM To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis.METHODS Acute colitis was induced by 3%(w/v)dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d.Concurrently,mice with colitis were administered 0.2 mL UCB(400μmol/L)by intra-gastric gavage for 7 d.Disease activity index(DAI)was monitored daily.Mice were sacrificed at the end of the experiment.The length of the colon and weight of the spleen were recorded.Serum level of D-lactate,intestinal digestive proteases activity,and changes to the gut flora were analyzed.In addition,colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins.RESULTS Mice treated with UCB had significantly relieved severity of colitis,including lower DAI,longer colon length,and lower spleen weight(colon length:4.92±0.09 cm vs 3.9±0.15 cm;spleen weight:0.33±0.04 vs 0.74±0.04,P<0.001).UCB administration inactivated digestive proteases(chymotrypsin:18.70±0.69 U/g vs44.81±8.60 U/g;trypsin:1.52±0.23 U/g vs 9.05±1.77 U/g,P<0.01),increased expression of tight junction(0.99±0.05 vs 0.57±0.03,P<0.001),decreased serum level of D-lactate(31.76±3.37μmol/L vs 54.25±1.45μmol/L,P<0.001),and lowered histopathological score(4±0.57 vs 7±0.57,P<0.001)and activity of myeloperoxidase(46.79±2.57 U/g vs 110.32±19.19 U/g,P<0.001).UCB also regulated the intestinal microbiota,inhibited expression of tumor necrosis factor(TNF)αand interleukin 1β(TNF-α:52.61±7.81 pg/mg vs 105.04±11.92 pg/mg,interleukin 1β:13.43±1.68 vs 32.41±4.62 pg/mg,P<0.001),decreased expression of Toll-like receptor 4(0.61±0.09 vs 1.07±0.03,P<0.001)and myeloid differentiation primary response gene 88(0.73±0.08 vs 1.01±0.07,P<0.05),and increased expression of TNF-receptor-associated factor 6(0.79±0.02 vs0.43±0.09 P<0.05)and inhibitor of kappa Bα(0.93±0.07 vs 0.72±0.07,P<0.05)in the colon.CONCLUSION UCB can protect intestinal barrier function,regulate normal intestinal homeostasis,and suppress inflammation via the Toll-like receptor 4/nuclear factor-κB signaling pathway.展开更多
AIM： To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS： Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2...AIM： To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS： Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2005. Of the 96 patients, 20 were initially treated with surgery （n = 2 R0 / n = 18 R1）. In non-operated patients, data analysis was performed retrospectively. RESULTS： Among the 96 patients, 76 were treated with endoscopic transpapillary （ERC, n = 45） and/or percutaneous transhepatic biliary drainage （PTBD, n = 31）. The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 ± 296 d. The mean survival time of patients with initial bilirubin levels 〉 10 mg/dL was significantly lower （P 〈 0.001） than patients with bilirubin levels 〈 10 mg/dL. The mean survival time of patients with Bismuth stage Ⅱ （n = 8）, Ⅲ （n = 28） and Ⅳ （n = 40） was 496 =1= 300 d, 441 ± 385 d and 274 ± 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant benefidal effect on the mean survival time （ERC vs PTBD, P = 0.806）. CONCLUSION： Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated.展开更多
AIM:To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice(BJ) and malignant jaundice(MJ).METHODS:All patients admitted for obstructive jaundi...AIM:To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice(BJ) and malignant jaundice(MJ).METHODS:All patients admitted for obstructive jaundice,in the period 2005-2009,were prospectively enrolled in the study,obtaining a total of 102 patients.On admission,all patients underwent complete standard blood test examinations including C-reactive protein(CRP),bilirubin,CA19-9.Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels(total bilirubin > 2.0 mg/dL).The standard cut-off level for CA19-9 was 32 U/mL,whereas for CRP this was 1.5 mg/L.The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value.The patients were divided into 2 groups,MJ and BJ,and after the adjustment a comparison between the 2 groups of patients was performed.Sensitivity,specificity and positive predictive values were calculated before and after the adjustment.RESULTS:Of the 102 patients,51 were affected by BJ and 51 by MJ.Pathologic CA19-9 levels were found in 71.7% of the patients.In the group of 51 BJ patients there were 29(56.9%) males and 22(43.1%) females with a median age of 66 years(range 24-96 years),whereas in the MJ group there were 24(47%) males and 27(53%) females,with a mean age of 70 years(range 30-92 years).Pathologic CA19-9 serum level was found in 82.3% of MJ.CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ.Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ(P = 0.000 and P = 0.02),while the CRP level was significantly higher in BJ(P = 0.000).Considering a CA19-9 cut-off level of 32 U/mL,82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9(P = 0.002).A CA19-9 cut-off of 100 U/mL increases the difference between the two groups:35.3% in BJ and 68.6% in MJ(P = 0.0007).Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value(P = 0.003),while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value(P = 0.000004).Sensitivity,specificity,positive predictive values of CA19-9 > 32 U/mL were 82.3%,45% and 59.1%;when the cutoff was CA19-9 > 100 U/mL they were,respectively,68.6%,64.7% and 66%.When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values,these became 49%,78.4%,69.4% and 76.5%,68.6%,70.9%,respectively.CONCLUSION:The present study proposes CRP as a new and useful correction factor to improve the diag-nostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.展开更多
The activation of heme oxygenase-1(HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catab...The activation of heme oxygenase-1(HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide(CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection.In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload(with signs of a chronic hepatitis) and iron deficiency anemia(with paradoxical increased levels of ferritin).Hypoxia induces HO-1 expression in multiple rodent,bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types(endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.展开更多
AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis(LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded...AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis(LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded.METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health(Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM(49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012.RESULTS: The baseline serum direct bilirubin concentration was(median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin(2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin wasindependently associated with LNM(OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that:(1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification;(2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and(3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis.CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.展开更多
AIM: To assess the diagnostic value of a combination of continuous intragastric pH and bilirubin monitoring in the detection of duodenogastric reflux (DGR), and the effects of diet on the bilirubin absorbance. METHODS...AIM: To assess the diagnostic value of a combination of continuous intragastric pH and bilirubin monitoring in the detection of duodenogastric reflux (DGR), and the effects of diet on the bilirubin absorbance. METHODS: 30 healthy volunteers were divided into two groups: standard diet group (Group 1) 18 cases, free diet group (Group 2)12 cases. Each subjects were subjected to simultaneous 24-hour intragastric pH and spectrophotometric bilirubin concentration monitoring (Bilitec 2000). RESULTS: There was no difference of preprandial phase bilirubin absorbance between two groups. The absorbance of postprandial phase was significantly increased in group 2 than group 1. There was no difference between preprandial phase and postprandial phase absorbance in group 1. Postprandial phase absorbance was significantly higher in group 2. In a comparison of bile reflux with intragastric pH during night time, there were 4 types of reflux: Simultaneous increase in absorbance and pH in only 19.6%, increase in bilirubin with unchanged pH 33.3%, pH increase with unchanged absorbance 36.3%, and both unchanged in 10.8%. Linear regression analysis showed no correlation between percentage total time of pH【4 and percentage total time of absorbance】0.14, r=0.068 P【0.05. CONCLUSION: Because of the dietary effect, high absorbance fluids or foods should be avoided in detection. Intragastric pH and bilirubin monitoring separately predict the presence of duodenal (and/or pancreatic) reflux and bile reflux. They can not substitute for each other. The detection of DGR is improved if the two parameters are combined simultaneously.展开更多
AIM： To study the factors that may affect survival of cholangiocarcinoma in Lebanon. METHODS： A retrospective review of the medical records of 55 patients diagnosed with cholangio- carcinoma at the American Universi...AIM： To study the factors that may affect survival of cholangiocarcinoma in Lebanon. METHODS： A retrospective review of the medical records of 55 patients diagnosed with cholangio- carcinoma at the American University of Beirut between 1990 and 2005 was conducted. Univariate and multivariate analyses were performed to determine the impact of surgery, chemotherapy, body mass index, bilirubin level and other factors on survival. RJ^SULTS： The median survival of all patients was 8.57 mo （0.03-105.2）. Univariate analysis showed that low bilirubin level （〈 10 mg/dL）, radical surgery and chemotherapy administration were significantly associated with better survival （P = 0.012, 0.038 and 0.038, respectively）, in subgroup analysis on patients who had no surgery, chemotherapy administration prolonged median survival significantly （17.0 mo vs 3.5 mo, P = 0.001）. Multivariate analysis identified only low bilirubin level 〈 10 mg/dL and chemotherapy administration as independent predictors associated with better survival （P 〈 0.05）. CONCLUSION： Our data show that palliative and postoperative chemotherapy as well as a bilirubin level 〈 10 mg/dL are independent predictors of a significant increase in survival in patients with cholangiocarcinoma.展开更多
AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS...AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.展开更多
Objective:To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl_4 intoxicated Swiss albino mice.Methods:first group of mice(n=5) received CCl_4 treatment at a dos...Objective:To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl_4 intoxicated Swiss albino mice.Methods:first group of mice(n=5) received CCl_4 treatment at a dose of 0.5 mL/kg bw(i.p.) for 7 days.Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for IS days.The third group was given both the turmeric extract(for 15 days,orally) and CCl_4(for last 7 days,i.p.).The fourth group was kept as a control.To study the liver function,the transaminase enzymes(SGOT and SGPT) and bilirubin level were measured in the serum of respective groups.For assaying the immunotherapeutic action of Curcuma longa(C.longa),non specific host response parameters like morphological alteration,phagocytosis,nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.Results:The result of present study suggested that CCl_4 administration increased the level of SCOT and SGPT and bilirubin level in serum.However,the aqueous extract of turmeric reduced the level of SGOT, SCFT and bilirubin in CCl_4 intoxicated mice.Apart from damaging the liver system,CCl_4 also reduced non specific host response parameters like morphological alteration,phagocytosis, nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages.Administration of aqueous extract of C.longa offered significant protection from these damaging actions of CCl_4 on the non specific host response in the peritoneal macrophages of CCl_4 intoxicated mice.Conclusions:In conclusion,the present study suggests that C.longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.展开更多
基金financially supported by the International Cooperation Program of the Ministry of Science and Technology of Hubei Province(No.2023EHA069)Shenzhen Science and Technology Program(No.JCYJ20230807143702005)the National Foreign Experts Program(No.G2022027015L)。
文摘Liver is a vital organ in the human body and plays a central role in the metabolism and detoxification of endotoxins and exotoxins.Bilirubin is an endotoxin derived from hemoglobin(Hb).Removing excess bilirubin in the blood is crucial for the treatment of liver diseases.Hemoperfusion,which relies on adsorbents to efficiently adsorb toxins,is a widely applied procedure for the removal of blood toxins.To broaden and improve the range and performance of hemoperfusion adsorbents,we synthesized cationic hyper crosslinked polymers(HCPs)with strong affinity for bilirubin.This material exhibited outstanding adsorption performance,with a maximum adsorption capacity of 934 mg/g and a removal efficiency of 96%.Further investigation confirmed their excellent selectivity,reusability,and biocompatibility.These findings expand the potential applications of HCPs and provide insight into strategies for constructing promising hemoperfusion adsorbent materials.
文摘BACKGROUND Gastric cancer is the most common malignancy of the digestive system and surgical resection is the primary treatment.Advances in surgical technology have reduced the risk of complications after radical gastrectomy;however,post-surgical pancreatic fistula remain a serious issue.These fistulas can lead to abdominal infections,anastomotic leakage,increased costs,and pain;thus,early diagnosis and prevention are crucial for a better prognosis.Currently,C-reactive protein(CRP),procalcitonin(PCT),and total bilirubin(TBil)levels are used to predict post-operative infections and anastomotic leakage.However,their predictive value for pancreatic fistula after radical gastrectomy for gastric cancer remains unclear.The present study was conducted to determine their predictive value.AIM To determine the predictive value of CRP,PCT,and TBil levels for pancreatic fistula after gastric cancer surgery.METHODS In total,158 patients who underwent radical gastrectomy for gastric cancer at our hospital between January 2019 and January 2023 were included.The patients were assigned to a pancreatic fistula group or a non-pancreatic fistula group.Multivariate logistic analysis was conducted to assess the factors influencing development of a fistula.Receiver operating characteristic(ROC)curves were used to determine the predictive value of serum CRP,PCT,and TBil levels on day 1 postsurgery.RESULTS On day 1 post-surgery,the CRP,PCT,and TBil levels were significantly higher in the pancreatic fistula group than in the non-pancreatic fistula group(P<0.05).A higher fistula grade was associated with higher levels of the indices.Univariate analysis revealed significant differences in the presence of diabetes,hyperlipidemia,pancreatic injury,splenectomy,and the biomarker levels(P<0.05).Logistic multivariate analysis identified diabetes,hyperlipidemia,pancreatic injury,CRP level,and PCT level as independent risk factors.ROC curves yielded predictive values for CRP,PCT,and TBil levels,with the PCT level having the highest area under the curve(AUC)of 0.80[95%confidence interval(CI):0.72-0.90].Combined indicators improved the predictive value,with an AUC of 0.86(95%CI:0.78-0.93).CONCLUSION Elevated CRP,PCT,and TBil levels predict risk of pancreatic fistula post-gastrectomy for gastric cancer.
基金funded by the Indian Council of Medical Research(ICMR),New Delhi,Government of India under Grant No.EM/SG/Dev.Res/124/0812-2023.
文摘Jaundice,common condition in newborns,is characterized by yellowing of the skin and eyes due to elevated levels of bilirubin in the blood.Timely detection and management of jaundice are crucial to prevent potential complications.Traditional jaundice assessment methods rely on visual inspection or invasive blood tests that are subjective and painful for infants,respectively.Although several automated methods for jaundice detection have been developed during the past few years,a limited number of reviews consolidating these developments have been presented till date,making it essential to systematically evaluate and present the existing advancements.This paper fills this gap by providing a thorough survey of automated methods for jaundice detection in neonates.The primary focus of the survey is to review the existing methodologies,techniques,and technologies used for neonatal jaundice detection.The key findings from the review indicate that image-based bilirubinometers and transcutaneous bilirubinometers are promising non-invasive alternatives,and provide a good trade-off between accuracy and ease of use.However,their effectiveness varies with factors like skin pigmentation,gestational age,and measurement site.Spectroscopic and biosensor-based techniques show high sensitivity but need further clinical validation.Despite advancements,several challenges including device calibration,large-scale validation,and regulatory barriers still haunt the researchers.Standardization,regulatory compliances,and seamless integration into healthcare workflows are the key hurdles to be addressed.By consolidating the current knowledge and discussing the challenges and opportunities in this field,this survey aims to contribute to the advancement of automatic jaundice detection and ultimately improve neonatal care.
基金Supported by the Medical Discipline Construction Project of Pudong Health Committee of Shanghai,No.PWZzb2022-09Nanning City Science Research and Technology Development Program,No.ZC20233017and Guangxi Medical and Health Appropriate Technology Development and Promotion Project,No.S2021061.
文摘BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.
文摘Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those involving hemolysis or impaired erythropoiesis,may play a significant role in the formation of gallblad-der stones,predominantly pigment stones.This review explores the pathophysio-logical mechanisms linking hematological disorders,such as hemolytic anemias,myeloproliferative disorders,and hematological malignancies,with gallbladder stone development.We also examine the influence of treatments for hemato-logical conditions,such as blood transfusions and chemotherapy,on gallstone risk.Additionally,this article discusses the clinical implications of gallbladder stones in patients with hematological disorders,including diagnostic challenges,management strategies,and surgical considerations.By providing a compre-hensive overview of current knowledge,this review aims to highlight the need for further research into the interplay between hematological disorders and gall-bladder stones,potentially improving preventive and therapeutic strategies in these patient populations.
文摘Hereditary spherocytosis(HS),a common inherited hemolytic anemia,is characterized by red blood cell membrane protein defects leading to chronic hemolysis.This condition significantly predisposes patients to gallstone disease,including both gallbladder and bile duct stones,due to excessive bilirubin production from hemolysis.Gallstones in HS patients,primarily composed of bilirubin,can lead to complications such as cholecystitis,cholangitis,and obstructive jaundice.This review provides a comprehensive landscape of the pathophysiological mechanisms linking HS to gallstone formation,emphasizing the roles of hemolysis,bile composition,and genetic factors.It also discusses the clinical manifestations of gallstone disease in HS,including recurrent jaundice and biliary obstruction,and highlights the diagnostic value of imaging modalities such as ultrasonography and magnetic resonance cholangiopancreatography.Furthermore,current management strategies,including splenectomy,cholecystectomy,and endoscopic approaches for bile duct stones,are examined in the context of HS.By synthesizing existing knowledge,this review aims to provide insights into improving the diagnosis,prevention,and treatment of gallstone disease in patients with HS,while identifying gaps for future research.
基金Supported by Natural Science Foundation of Shaanxi Province,No.2024JC-YBQN-0828 and No.2024JC-YBMS-765Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University,No.XJTU1AF-CRF-2022-036National Innovation Center for Advanced Medical Devices,No.NMED2023AGP-013.
文摘BACKGROUND Diabetic retinopathy(DR)is a major cause of visual impairment and blindness.However,the current DR biomarkers are insufficient for accurately predicting its onset.AIM To identify a novel marker for predicting the risk of developing DR in patients with type 2 diabetes mellitus(T2DM).METHODS We conducted a cross-sectional study involving 6993 hospitalized T2DM patients between 2013 and 2020.Patients were divided into two groups:The DR group and the non-DR group.Data were analyzed using univariate,correlation,multivariate,subgroup,and receiver operating characteristic curve analyses.RESULTS Total bilirubin,indirect bilirubin(IBIL),and direct bilirubin were negatively correlated with the risk of developing DR(P<0.001).Moreover,these three factors were all positively correlated with clinical indicators related to DR,including the estimated glomerular filtration rate,the albumin/creatinine ratio,and the 1,25-dihydroxyvitamin D3 level(P<0.001).After adjusting for multiple variables,greater IBIL levels remained independently associated with a lower risk of developing DR(odds ratio=0.500;95%confidence interval:0.363-0.686;P<0.001).The optimal IBIL cutoff point for predicting the risk of DR in male patients with elevated diastolic blood pressure was 0.655μmol/dL(area under the curve=0.662).CONCLUSION These findings suggest that IBIL could be a valuable biomarker for predicting DR risk,offering a noninvasive,cost-effective,and readily available clinical tool for the early identification of high-risk patients.Future multicenter and longitudinal studies are warranted to validate these findings and further explore the biological mechanisms underlying the protective role of IBIL in DR.
基金Supported by Shandong Province Biliary Pancreatic Cancer Clinical Quality Specialty Construction Fund,No.SLCZDZK-2401.
文摘BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle factors,and diseases.Obstructive jaundice is one of the most common pathophysiological changes in patients needing hepatobiliary or pancreatic operations that can adversely affect the tissue and organ function throughout the human body.However,the effects of obstructive jaundice on the occurrence of sarcopenia remain unclear.AIM To investigate the incidence of sarcopenia in patients with surgical obstructive jaundice and the association of sarcopenia with postoperative outcome.METHODS This cross-sectional study was conducted from December 2019 to January 2024.Data retrieved included patient demographics,disease entities,sarcopenia-related parameters(including grip strength,6-m walking time,and limb skeletal muscle mass index),postoperative complications,and length of hospital stay.Sarcopenia was confirmed using Asian Working Group standards.Logistic regression was used to analyze the relationship between total bilirubin level and sarcopenia.The factors influencing sarcopenia in patients with surgical obstructive jaundice and association of sarcopenia with postoperative complications were also investigated.RESULTS Overall,1708 patients met the inclusion criteria,with a mean age of 60.09±13.52 years(sex:52.28%male).There were 383 patients(22.42%)with obstructive jaundice and 1325(77.58%)without jaundice.Sarcopenia,low walking speed,low grip strength,and low limb skeletal muscle index were more prevalent in patients with obstructive jaundice than nonobstructive jaundice.The odds ratio(OR)for sarcopenia in patients with obstructive jaundice was 1.689[95%confidence interval(CI):1.295-2.203,P<0.001],indicating that jaundice is a significant risk factor for sarcopenia.The occurrence of sarcopenia was higher in patients with severe obstructive jaundice than mild obstructive jaundice(39.3%vs 22.8%,P<0.05).Obstructive jaundice was positively correlated with reduced walking speed(OR=1.627,95%CI:1.185-2.234,P=0.003)and decreased grip strength(OR=1.669,95%CI:1.212-2.300,P=0.002).Age(OR=1.077,95%CI:1.040-1.114,P<0.001)and body mass index(OR=0.703,95%CI:0.630-0.784,P<0.001)were independent risk factors of sarcopenia in patients with obstructive jaundice.Patients with obstructive jaundice and sarcopenia had a higher rate of postoperative complications(46.3%vs 33.1%,P=0.032),longer postoperative hospital stays(11.33±6.75 days vs 9.19±7.32 days,P=0.016),and longer total hospital stays(17.10±7.69 days vs 15.98±8.55 days,P=0.032)than those without sarcopenia.CONCLUSION Sarcopenia is more prevalent in patients with obstructive jaundice and is positively correlated with the degree of jaundice.Sarcopenia prolongs hospital stays and is associate with postoperative complications.
文摘Acute Bilirubin Encephalopathy(ABE)is a significant threat to neonates and it leads to disability and high mortality rates.Detecting and treating ABE promptly is important to prevent further complications and long-term issues.Recent studies have explored ABE diagnosis.However,they often face limitations in classification due to reliance on a single modality of Magnetic Resonance Imaging(MRI).To tackle this problem,the authors propose a Tri-M2MT model for precise ABE detection by using tri-modality MRI scans.The scans include T1-weighted imaging(T1WI),T2-weighted imaging(T2WI),and apparent diffusion coefficient maps to get indepth information.Initially,the tri-modality MRI scans are collected and preprocessesed by using an Advanced Gaussian Filter for noise reduction and Z-score normalisation for data standardisation.An Advanced Capsule Network was utilised to extract relevant features by using Snake Optimization Algorithm to select optimal features based on feature correlation with the aim of minimising complexity and enhancing detection accuracy.Furthermore,a multi-transformer approach was used for feature fusion and identify feature correlations effectively.Finally,accurate ABE diagnosis is achieved through the utilisation of a SoftMax layer.The performance of the proposed Tri-M2MT model is evaluated across various metrics,including accuracy,specificity,sensitivity,F1-score,and ROC curve analysis,and the proposed methodology provides better performance compared to existing methodologies.
基金Supported by Grants DK54012,DK73917,to Wang DQ-HDK36588,DK34854,and DK73687,to Carey MCall from the National Institutes of Health(US Public Health Service)
文摘Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, ox and common carp biles approximately in the Zhou dynasty (c. 1046-256 BCE). Overall, different animal biles were prescribed principally for the treatment of liver, biliary, skin (including burns), gynecological and heart diseases, as well as diseases of the eyes, ears, nose, mouth and throat. We present an informed opinion of the clinical efficacy of the medicinal uses of the different animal biles based on their presently known principal chemical components which are mostly steroidal detergent-like molecules and the membrane lipids such as unesterified cholesterol and mixed phosphatidylcholines and sometimes sphingomyelin, as well as containing lipopigments derived from heme principally bilirubin glucuronides. All of the available information on the ethnopharmacological uses of biles in TCM were collated from the rich collection of ancient Chinese books on materia medica held in libraries in China and United States and the composition of various animal biles was based on rigorous separatory and advanced chemical identification techniques published since the mid-20<sup>th</sup> century collected via library (Harvard’s Countway Library) and electronic searches (PubMed and Google Scholar). Our analysis of ethnomedical data and information on biliary chemistry shows that specific bile salts, as well as the common bile pigment bilirubin and its glucuronides plus the minor components of bile such as vitamins A, D, E, K, as well as melatonin (N-acetyl-5-methoxytryptamine) are salutary in improving liver function, dissolving gallstones, inhibiting bacterial and viral multiplication, promoting cardiac chronotropsim, as well as exhibiting anti-inflammatory, anti-pyretic, anti-oxidant, sedative, anti-convulsive, anti-allergic, anti-congestive, anti-diabetic and anti-spasmodic effects. Pig, wild boar and human biles diluted with alcohol were shown to form an artificial skin for burns and wounds one thousand years ago in the Tang dynasty (618-907 CE). Although various animal biles exhibit several generic effects in common, a number of biles appear to be advantageous for specific therapeutic indications. We attempt to understand these effects based on the pharmacology of individual components of bile as well as attempting to identify a variety of future research needs.
基金Supported by grants from the National Natural Foundation of China,No.81703232
文摘BACKGROUND Unconjugated bilirubin(UCB)is generally considered toxic but has gained recent prominence for its anti-inflammatory properties.However,the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved.AIM To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis.METHODS Acute colitis was induced by 3%(w/v)dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d.Concurrently,mice with colitis were administered 0.2 mL UCB(400μmol/L)by intra-gastric gavage for 7 d.Disease activity index(DAI)was monitored daily.Mice were sacrificed at the end of the experiment.The length of the colon and weight of the spleen were recorded.Serum level of D-lactate,intestinal digestive proteases activity,and changes to the gut flora were analyzed.In addition,colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins.RESULTS Mice treated with UCB had significantly relieved severity of colitis,including lower DAI,longer colon length,and lower spleen weight(colon length:4.92±0.09 cm vs 3.9±0.15 cm;spleen weight:0.33±0.04 vs 0.74±0.04,P<0.001).UCB administration inactivated digestive proteases(chymotrypsin:18.70±0.69 U/g vs44.81±8.60 U/g;trypsin:1.52±0.23 U/g vs 9.05±1.77 U/g,P<0.01),increased expression of tight junction(0.99±0.05 vs 0.57±0.03,P<0.001),decreased serum level of D-lactate(31.76±3.37μmol/L vs 54.25±1.45μmol/L,P<0.001),and lowered histopathological score(4±0.57 vs 7±0.57,P<0.001)and activity of myeloperoxidase(46.79±2.57 U/g vs 110.32±19.19 U/g,P<0.001).UCB also regulated the intestinal microbiota,inhibited expression of tumor necrosis factor(TNF)αand interleukin 1β(TNF-α:52.61±7.81 pg/mg vs 105.04±11.92 pg/mg,interleukin 1β:13.43±1.68 vs 32.41±4.62 pg/mg,P<0.001),decreased expression of Toll-like receptor 4(0.61±0.09 vs 1.07±0.03,P<0.001)and myeloid differentiation primary response gene 88(0.73±0.08 vs 1.01±0.07,P<0.05),and increased expression of TNF-receptor-associated factor 6(0.79±0.02 vs0.43±0.09 P<0.05)and inhibitor of kappa Bα(0.93±0.07 vs 0.72±0.07,P<0.05)in the colon.CONCLUSION UCB can protect intestinal barrier function,regulate normal intestinal homeostasis,and suppress inflammation via the Toll-like receptor 4/nuclear factor-κB signaling pathway.
文摘AIM： To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS： Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995-2005. Of the 96 patients, 20 were initially treated with surgery （n = 2 R0 / n = 18 R1）. In non-operated patients, data analysis was performed retrospectively. RESULTS： Among the 96 patients, 76 were treated with endoscopic transpapillary （ERC, n = 45） and/or percutaneous transhepatic biliary drainage （PTBD, n = 31）. The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 ± 296 d. The mean survival time of patients with initial bilirubin levels 〉 10 mg/dL was significantly lower （P 〈 0.001） than patients with bilirubin levels 〈 10 mg/dL. The mean survival time of patients with Bismuth stage Ⅱ （n = 8）, Ⅲ （n = 28） and Ⅳ （n = 40） was 496 =1= 300 d, 441 ± 385 d and 274 ± 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant benefidal effect on the mean survival time （ERC vs PTBD, P = 0.806）. CONCLUSION： Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated.
文摘AIM:To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice(BJ) and malignant jaundice(MJ).METHODS:All patients admitted for obstructive jaundice,in the period 2005-2009,were prospectively enrolled in the study,obtaining a total of 102 patients.On admission,all patients underwent complete standard blood test examinations including C-reactive protein(CRP),bilirubin,CA19-9.Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels(total bilirubin > 2.0 mg/dL).The standard cut-off level for CA19-9 was 32 U/mL,whereas for CRP this was 1.5 mg/L.The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value.The patients were divided into 2 groups,MJ and BJ,and after the adjustment a comparison between the 2 groups of patients was performed.Sensitivity,specificity and positive predictive values were calculated before and after the adjustment.RESULTS:Of the 102 patients,51 were affected by BJ and 51 by MJ.Pathologic CA19-9 levels were found in 71.7% of the patients.In the group of 51 BJ patients there were 29(56.9%) males and 22(43.1%) females with a median age of 66 years(range 24-96 years),whereas in the MJ group there were 24(47%) males and 27(53%) females,with a mean age of 70 years(range 30-92 years).Pathologic CA19-9 serum level was found in 82.3% of MJ.CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ.Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ(P = 0.000 and P = 0.02),while the CRP level was significantly higher in BJ(P = 0.000).Considering a CA19-9 cut-off level of 32 U/mL,82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9(P = 0.002).A CA19-9 cut-off of 100 U/mL increases the difference between the two groups:35.3% in BJ and 68.6% in MJ(P = 0.0007).Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value(P = 0.003),while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value(P = 0.000004).Sensitivity,specificity,positive predictive values of CA19-9 > 32 U/mL were 82.3%,45% and 59.1%;when the cutoff was CA19-9 > 100 U/mL they were,respectively,68.6%,64.7% and 66%.When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values,these became 49%,78.4%,69.4% and 76.5%,68.6%,70.9%,respectively.CONCLUSION:The present study proposes CRP as a new and useful correction factor to improve the diag-nostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.
基金Supported by Brazilian Foundation-FAPESP(Fundao deapoio à pesquisa do Estado de So Paulo),No.07/07139-3,10/02024-6 and CNPq
文摘The activation of heme oxygenase-1(HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide(CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection.In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload(with signs of a chronic hepatitis) and iron deficiency anemia(with paradoxical increased levels of ferritin).Hypoxia induces HO-1 expression in multiple rodent,bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types(endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.
基金Supported by the National Specific Research Project for Health and Welfare of ChinaNo.200902002-1+3 种基金the Research Fund of Beijing Municipal Science and Technology CommissionNo.Z111107067311021Beijing NOVA ProgrammeNo.Z131107000413067
文摘AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis(LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded.METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health(Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM(49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012.RESULTS: The baseline serum direct bilirubin concentration was(median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin(2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin wasindependently associated with LNM(OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that:(1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification;(2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and(3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis.CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.
基金the Public Health Ministry Foundation of China,No.06-9602-13
文摘AIM: To assess the diagnostic value of a combination of continuous intragastric pH and bilirubin monitoring in the detection of duodenogastric reflux (DGR), and the effects of diet on the bilirubin absorbance. METHODS: 30 healthy volunteers were divided into two groups: standard diet group (Group 1) 18 cases, free diet group (Group 2)12 cases. Each subjects were subjected to simultaneous 24-hour intragastric pH and spectrophotometric bilirubin concentration monitoring (Bilitec 2000). RESULTS: There was no difference of preprandial phase bilirubin absorbance between two groups. The absorbance of postprandial phase was significantly increased in group 2 than group 1. There was no difference between preprandial phase and postprandial phase absorbance in group 1. Postprandial phase absorbance was significantly higher in group 2. In a comparison of bile reflux with intragastric pH during night time, there were 4 types of reflux: Simultaneous increase in absorbance and pH in only 19.6%, increase in bilirubin with unchanged pH 33.3%, pH increase with unchanged absorbance 36.3%, and both unchanged in 10.8%. Linear regression analysis showed no correlation between percentage total time of pH【4 and percentage total time of absorbance】0.14, r=0.068 P【0.05. CONCLUSION: Because of the dietary effect, high absorbance fluids or foods should be avoided in detection. Intragastric pH and bilirubin monitoring separately predict the presence of duodenal (and/or pancreatic) reflux and bile reflux. They can not substitute for each other. The detection of DGR is improved if the two parameters are combined simultaneously.
文摘AIM： To study the factors that may affect survival of cholangiocarcinoma in Lebanon. METHODS： A retrospective review of the medical records of 55 patients diagnosed with cholangio- carcinoma at the American University of Beirut between 1990 and 2005 was conducted. Univariate and multivariate analyses were performed to determine the impact of surgery, chemotherapy, body mass index, bilirubin level and other factors on survival. RJ^SULTS： The median survival of all patients was 8.57 mo （0.03-105.2）. Univariate analysis showed that low bilirubin level （〈 10 mg/dL）, radical surgery and chemotherapy administration were significantly associated with better survival （P = 0.012, 0.038 and 0.038, respectively）, in subgroup analysis on patients who had no surgery, chemotherapy administration prolonged median survival significantly （17.0 mo vs 3.5 mo, P = 0.001）. Multivariate analysis identified only low bilirubin level 〈 10 mg/dL and chemotherapy administration as independent predictors associated with better survival （P 〈 0.05）. CONCLUSION： Our data show that palliative and postoperative chemotherapy as well as a bilirubin level 〈 10 mg/dL are independent predictors of a significant increase in survival in patients with cholangiocarcinoma.
基金Supported by The Dietmar Hopp Foundation and the Manfred Lautenschlger Foundation,an Olympia-Morata fellowship of the University of Heidelberg (Millonig G)
文摘AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.
文摘Objective:To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl_4 intoxicated Swiss albino mice.Methods:first group of mice(n=5) received CCl_4 treatment at a dose of 0.5 mL/kg bw(i.p.) for 7 days.Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for IS days.The third group was given both the turmeric extract(for 15 days,orally) and CCl_4(for last 7 days,i.p.).The fourth group was kept as a control.To study the liver function,the transaminase enzymes(SGOT and SGPT) and bilirubin level were measured in the serum of respective groups.For assaying the immunotherapeutic action of Curcuma longa(C.longa),non specific host response parameters like morphological alteration,phagocytosis,nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.Results:The result of present study suggested that CCl_4 administration increased the level of SCOT and SGPT and bilirubin level in serum.However,the aqueous extract of turmeric reduced the level of SGOT, SCFT and bilirubin in CCl_4 intoxicated mice.Apart from damaging the liver system,CCl_4 also reduced non specific host response parameters like morphological alteration,phagocytosis, nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages.Administration of aqueous extract of C.longa offered significant protection from these damaging actions of CCl_4 on the non specific host response in the peritoneal macrophages of CCl_4 intoxicated mice.Conclusions:In conclusion,the present study suggests that C.longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.
