Exploring the effect of Bushen Bitong recipe-containing serum on IL-1β-induced chondrocyte apoptosis based on SOX9/NF-κB/MMP-13 signaling pathway

Objective:To observe the effect and possible mechanism of action of Bushen Bitong recipe(BSBT)containing serum on IL-1β-induced chondrocyte apoptosis.Methods:Generation 3 rat chondrocytes were randomized into Control,IL-1β,IL-1β+BSBT(L),IL-1β+BSBT(M),and IL-1β+BSBT(H)groups(5%,10%and 15%BSBT-containing serum),and then 24h after intervention respectively,the cell proliferation and Apoptosis rate;Western blot detected the expression levels of Bcl-2,BAX,Caspase-3,SOX9,NF-κB p65,MMP-13 proteins in chondrocytes.ELISA detected the levels of TNF-α,IL-6,and bFGF in the supernatants of chondrocyte culture.Results:Compared with Control group,cell proliferation activity decreased,apoptosis rate increased,NF-κB p65,MMP-13 protein level and TNF-α,IL-6 level increased,and SOX9 protein level and bFGF level decreased in IL-1βgroup;compared with IL-1βgroup,different concentrations of BSBT-containing serum group,cell proliferation activity increased,and apoptosis rate decreased.NF-κB p65,MMP-13 protein level and TNF-α,IL-6 level decreased,SOX9 protein level and bFGF level increased;compared with IL-1β+BSBT(L)group,cell proliferation activity increased,apoptosis rate decreased in IL-1β+BSBT(M)and IL-1β+BSBT(H)groups,and NF-κB p65,MMP-13 protein level and TNF-αlevel decreased.13 protein levels and TNF-αand IL-6 levels decreased,and SOX9 protein levels and bFGF levels increased.Conclusion:BSBT-containing serum may promote IL-1β-induced proliferation of chondrocytes,reduce apoptosis,improve the microenvironment of chondrocytes,and promote cartilage repair through the SOX9/NF-κB/MMP-13 signaling pathway.

Overexpression of mitogen-activated protein kinase phosphatase-1 in endothelial cells reduces blood-brain barrier injury in a mouse model of ischemic stroke

Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.

Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature

BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely rare.To our knowledge,no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine.CASE SUMMARY Here,we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm×32 mm×30 mm in the terminal ileum.Based on computed tomography scan findings,the mass was initially suspected to be a lipoma.A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line.A biopsy of the upper portion suggested a juvenile polyp(JP).Owing to the patient’s advanced age,multiple comorbidities,and poor surgical tolerance,a modified endoscopic submucosal dissection was performed.Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top,demonstrating evidence of rupture and associated bleeding.The patient’s overall health remained satisfactory,with no recurrence of hematochezia during the six-month follow-up period.CONCLUSION This case report provides new evidence for the understanding of gastrointestinal collision tumors,emphasizing their diverse clinical presentations and histopathological characteristics.It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUND China has a high prevalence of hepatitis B virus(HBV),but most chronic hepatitis B(CHB)patients do not receive standardized antiviral therapy.There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998.The median follow-up times were 10 and 7 years,respectively.A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups.The median follow-up times were 8 and 7 years,respectively.Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma(HCC),and the Cox regression model was used to analyze the risk factors for HCC.RESULTS Among the patients in the non-antiviral group,16.9%had spontaneous decreases(HBeAg)seroconversion.In the antiviral group,87.2%of patients had undetectable HBV DNA,and 52%showed HBeAg seroconversion.Among CHB and hepatitis B cirrhosis patients,the cumulative incidence rates of HCC were 14.9%and 53.1%,respectively,in the non-antiviral group and were 10.7%and 31.9%,respectively,in the antiviral group.There was no difference between the two groups regarding the CHB patients(P=0.842),but there was a difference between the groups regarding the hepatitis B cirrhosis patients(P=0.026).The cumulative incidence rates of HCC were 1.6%and 22.3%(P=0.022)in the groups with and without spontaneous HBeAg seroconversion,respectively.The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6%and 19.1%,respectively(P=0.051).There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB(P=0.119),but there was a significant difference between the two groups regarding the patients with cirrhosis(P=0.004).The Cox regression model was used for regression of the corrected REACH-B score,which showed that alanine aminotransferase>400 U/L,history of diabetes,and family history of liver cancer were risk factors for HCC among men aged>40 years(P<0.05).Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and antiinflammatory therapy can reduce the risk of HCC.Antiviral therapy may mask the spontaneous serological response of some patients during CHB.Therefore,the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects

Non-alcoholic fatty liver disease(NAFLD) is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH) to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver transplantation.NAFLD and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2 D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in NAFLD.Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2 D.Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD.Therefore,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients.In the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways.We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients.The specific focus was liver histopathology as assessed by the invasive liver biopsy.Additionally,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.

Ovarian growing teratoma syndrome with multiple metastases in the abdominal cavity and liver:A case report

BACKGROUND Growing teratoma syndrome(GTS)is an unusual presentation of an amazing transformation of teratoma from malignant to benign on pathology during or after systemic or intraperitoneal chemotherapy.The definitive pathogenesis is still not fully understood due to the lack of large-sample studies.CASE SUMMARY A 53-year-old woman underwent radical surgery and postoperative intraperitoneal chemotherapy due to immature teratoma of the right ovary at the age of 28.She remained well during a 25-year follow-up period after surgery.Multiple asymptomatic solid masses were found in the liver on ultrasonography a month ago.Enhanced computed tomography(CT)of the abdomen revealed multiple masses in the abdominal cavity.The largest one was located in the posterior peritoneum next to the sixth segment of the right liver,about 7.9 cm×7.5 cm in size.Three masses were present inside the liver,and one mass was in the right pelvic floor.Multiple lumps in the abdominal cavity were completely removed by surgery.During the operation,multiple space-occupying lesions were seen,ranging in size from 0.5 to 3 cm,and grayish white in color and hard in texture.Ovarian GTS was finally diagnosed based on postoperative pathology.After surgery,she recovered uneventfully.During a 3-year follow-up,the patient remained free of the disease without any recurrence on CT scan.CONCLUSION GTS is a rare phenomenon characterized by conversion of immature teratoma to mature one during or after chemotherapy and presents as growing and metastasizing masses.The pathogenesis of GTS is unclear,and the prognosis is good after surgical resection.

The effects of nutritional ketosis induced by Bigu-herbs regimen and ketogenic diet on diseases and aging

The Bigu-herbs regimen,a Taoism(Taoism is an ancient Chinese Taoist philosophy system)special health-preserving technique to achieve longevity through strict abstinence from food,limits the intake of grains and uses herbs to replace normal diet to gain energy.Practicing Bigu-herbs regimen for several weeks to several years can make one lose weight,prevent diseases,and prolong life.The modern ketogenic diet(KD)mainly limits carbohydrate intake and increase fat intake.The low-carbohydrate,high-fat,and adequate protein diet is well known for its antiepileptic and neurotrophic effects.Limiting the intake of carbohydrate results in energy metabolism reprogramming to mobilize the steatolysis,energize and promote ketone bodies(KBs)production,achieving a state of nutritional ketosis(NK).The researchers summarized how ketone bodies or NK affects diseases and the aging process,as well as the side effects of KD.NK has a favorable effect on caloric intake,lipid parameters,glycemic index,and insulin sensitivity;moreover,it can be used as a treatment option for diabetes,obesity,and other metabolic disorders.NK is recognized as being neuroprotective and is good for epilepsy,Alzheimer’s disease,and emotional disturbance.Targeting the metabolic differences between tumor and normal cells,NK limits the use of glucose and impairs energy metabolism in cancer cells,inhibiting their growth and rendering them susceptible to clinical treatments.NK also affects inflammation and the release of cytokines,regulate gut flora,extend longevity and health span,and preserve physiologic functions.The side effects of KDs are controllable under the guidance of a specially trained dietitian and medical team.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis:a meta-analysis

Objective:To evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy(HIPEC)in the treatment of gastric cancer with peritoneal carcinomatosis.Methods:The relevant clinical controlled studies were retrieved from the databases of PubMed,Cochrane Library,Embase.Risk ratio(RR),as well as the respective 95%confidence interval(CI),was used as a statistical indicator.1-year survival,2-year survival,and safety were analyzed.Results:Two randomized controlled trials(RCTs)and 10 high-quality non-randomized controlled trials(NRCTs)were included,enrolling 837 patients(438 in the HIPEC group and 415 in the control group).Compared with the control group,HIPEC group turned out to be of greater improvement in long-term efficacy:1-year survival rate(1y-os)and 2-year survival rate(2y-os).Subgroup analysis of different treatment modes in NRCTs showed that,in terms of 1-year survival rate,(1)HIPEC combined with cytoreductive surgery(CRS)compared with CRS alone,RR=0.68,95%CI:(0.53,0.85);(2)HIPEC combined with intravenous chemotherapy±CRS versus chemotherapy alone,RR=0.54,95%CI:(0.39,0.74);(3)HIPEC combined with palliative gastrectomy versus palliative gastrectomy,RR=0.37,95%CI:(0.22,0.63).As for safety,there were no significant differences in adverse events between two groups.Conclusion:HIPEC can prolong the survival of gastric cancer patients with peritoneal carcinomatosis,and the incidences of adverse events were not increased.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

Perspectives on multidimensional assessment of post-stroke sequelae: fromclinimetrics to holism

In this work,we intended to connect clinimetrics with holism in traditional Chinese medicine towards multidimensional assessment of post-stroke sequelae in real-world setting,as a bridge between inheritance and innovation.Firstly,a systematic search of current evidence that supported integrated treatment of traditional Chinese and Western medicine for post-stroke sequelae sufferers was performed.Secondly,on the basis of available evidence,we presented couples of implications.Lastly,as psychosomatic perspective is one of the main academic paradigms of traditional Chinese medicine holism,we chiefly proposed comprehensive assessment for both motor and non-motor severities to probably match consonance with traditional Chinese medicine practice that treats psycho-/somatic-complains simultaneously.

New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report

BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have been linked to PFIC type 4(PFIC4),which predominantly presents in childhood.However,there are only limited data from adults with TJP2-related PFIC4.We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4.CASE SUMMARY The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers.In 2018,he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019.Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4(TJP2([NM_004817.3]:c.[3334C>T];[3334C>T])).The consanguineous family consists of the father and mother(both heterozygous)and their 12 children,of which five carry the variant in a homozygous state;however,these five siblings have highly variable expression of PFIC4.Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36.Two other homozygous brothers,age 23 and 19,and the homozygous sister,age 21,have elevated liver enzymes but presently no cirrhosis,which may suggest an age-dependent penetrance.In addition,five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state,respectively.CONCLUSION This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults.

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

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

A correlation of computed tomography perfusion and histopathology in tumor edges of hepatocellular carcinoma

BACKGROUND： The peripheral morphologic characteristics of hepatocellular carcinoma （HCC） reflect tumor growth patterns. Computed tomography （CT） perfusion is a new method to analyze hemodynamic changes in tissues. We assessed the relationship between CT perfusion and histopathologic findings in the periphery of HCC lesions. METHODS： Non-contrast CT, enhanced dual-phase CT, and CT perfusion were performed on 77 subjects （47 patients and 30 controls）. Based on the imaging findings of enhanced dual- phase CT, the tumor edges were classified into three types： type Ⅰ （sharp）; type Ⅱ （blurry）; and type Ⅲ （mixed）. The CT perfusion parameters included hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. The tissue sections from resected specimens were subjected to routine hematoxylin and eosin staining and immunohistochemical staining for CD34. The correlations between microvessel density （MVD） and the CT perfusion parameters were analyzed using Pearson＇s product-moment correlation coefficient. Changes in the perfusion parameters in tumor edges of different tumor types were evaluated. RESULTS： Type Ⅰ （sharp）： the pathologic findings showed fibrous connective tissue capsules in the tumor edges, and an MVD 〈30/ram2. Type Ⅱ （blurry）： the histology showed that the edges were clear with no capsules and an MVD 〉30/ram2. Type Ⅲ （mixed）： the pathology was similar to that of types I and II, and an MVD 〉30/mm~. Hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion were significantly increased in the tumor edges of HCC patients compared to those of the controls （P〈0.05）. The correlation between CT perfusion parameters and MVD was higher in blurry tumor edges of type II than in those of types Ⅰ or Ⅲ. CONCLUSION： CT perfusion imaging of tumor edges may be helpful in revealing histopathological features, and indirectly reflect angiogenic changes of HCCs.

Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Successful treatment of infantile hepatitis B with lamivudine: A case report

BACKGROUND How to treat infantile hepatitis B virus(HBV)infection remains a controversial issue.The nucleoside analogue lamivudine(LAM)has been approved to treat children(2 to 17 years old)with chronic hepatitis B.Here,we aimed to investigate the benefit of LAM treatment in infantile hepatitis B.CASE SUMMARY A 4-mo-old infant born to a hepatitis B surface antigen(HBsAg)-positive woman was found to be infected by HBV during a health checkup.Liver chemistry and HBV seromarker tests showed alanine aminotransferase of 106 U/L,HBsAg of 685.2 cut-off index,hepatitis B“e”antigen of 1454.0 cut-off index,and HBV DNA of>1.0×10^(9) IU/mL.LAM treatment(20 mg/d)was initiated,and after 19 mo,serum HBsAg was entirely cleared and hepatitis B surface antibody was present.The patient received LAM treatment for 2 years in total and has been followed for 3 years.During this period,serum hepatitis B surface antibody has been persistently positive,and serum HBV DNA was undetectable.CONCLUSION Early treatment of infantile hepatitis B with LAM could be safe and effective。

Emphysematous pyelonephritis:Six case reports and review of literature

BACKGROUND Emphysematous pyelonephritis(EPN)is a severe acute necrotizing infection of the renal parenchyma and surrounding tissues that causes the presence of gas in the renal parenchyma,collecting system,or perinephric tissue and has a poor prognosis.EPN occurs primarily in people with diabetes mellitus(DM),but can occur in those without DM when the associated renoureteral unit is obstructed.CASE SUMMARY We describe our experience with six patients who developed EPN.Five patients had DM,including one with diabetic ketoacidosis,one with multisystem involvements,including eye,lung and brain.Bilateral urolithiasis was present in one case,along with emphysematous cystitis.Unilateral kidney stones were present in one patient.One patient was an older man in poor general health.Five individuals survived and underwent surgical procedures including ureteral stent installation(Double J stent placement),percutaneous nephrostomy and perinephric abscess puncture drainage,while one died because the patient’s family chose to terminate therapy.Klebsiella pneumoniae and Escherichia coli were the microorganisms implicated.CONCLUSION We conclude that EPN is a potentially fatal illness.A positive outcome necessitates early detection.Therapeutic measures should be implemented as soon as a diagnosis is made.