OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

Background::As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.Methods::Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.Results::Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera ( Enterobacter and Enterococcus) are unaffected by rifaximin therapy. Conclusions::IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.Registration::Chinese Clinical Trial Registry, ChiCTR1800017911.

Four hundred and four male patients with primary gout were enrolled. According to the degree of nonalcoholic fatty liver diseases (NAFLD), the patients were divided into simple gout ( n=121), gout combined with mild NAFLD ( n=149) and gout combined with moderate-severe NAFLD ( n=134). The height, weight, waist, hip, blood pressure and blood biochemistry parameters of patients were measured. The degree of NAFLD was negatively correlated with the age of patients in three groups. The BMI, ratio of waist/hip, count of red cells, hemoglobin, hematocrit, red blood cell distribution width ( SD and CV), triglyceride, alanine aminotransferase and HOMA-IR were increased with the increasing of NAFLD severity (all P<0.05). Red blood cell count, hemoglobin, alanine aminotransferase, serum uric acid increased with the increasing of NAFLD severity (all P<0.05). Platelet, serum urea nitrogen and serum creatinine were decreased with the increase of NAFLD severity. Logistic regression showed that BMI, hemoglobin and HOMA-IR were independent risk factors for NAFLD. The prevalence and the severity of NAFLD was increased with increasing quadrates of hemoglobin. Taking group Q1 as a control, OR of NAFLD in group Q2 was 1.166(95 %CI:0.638-2.133), OR in group Q3 was 2.011(95 %CI:1.122-3.605)and OR in group Q4 was 3.120(95 %CI:1.613-6.034). The result indicates that hemoglobin levels are associated with the development and the severity of NAFLD in male patients with primary gout.

Objective To investigate the effects of Edaravone on cognitive dysfunction and on protein expression of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK)signaling pathway in elderly patients with acute ischemic stroke. Methods A total of 100 elderly patients with acute ischemic cerebral stroke admitted to our hospital from January 2011 to December 2015 were enrolled in this study.During the corresponding period ,100 healthy individuals receiving regular check-ups were selected as the control group. The effects of Edaravone on cognitive function in elderly patients with acute ischemic cerebral stroke were assessed.Serum proteins related to the MAPK/ERK signaling pathway were assayed. Results Elderly patients with acute ischemic stroke showed obvious cognitive dysfunction ,and scores on memory ,orientation ,attention ,calculation language and recall significantly decreased(P＜0.01)but returned to normal after Edaravone treatment (P＜0.01).Compared with the control group ,serum protein expression of rat sarcoma (Ras) ,rapidly accelerated fibrosarcoma(Raf) ,hypoxia inducible factor-1α(HIF-1α) ,connective tissue growth factor (CTGF),extracellular signal-regulated protein kinase(ERK1),ERK2 ,MAPK/ERK kinase(MEK), interleukin-1(IL-1) ,tumor necrosis factor-α(TNF-α) ,vascular endothelial growth factor (VEGF) , tissue inhibitor of metalloproteinase (TIMP) ,nerve growth factor (NGF)and its receptors was significantly downregulated(P＜0.01) ,while expression of leptin and its receptors was upregulated in elderly patients with acute ischemic cerebral stroke ( P ＜ 0.01 ). Expression levels of the above downregulated proteins clearly recovered after Edaravone treatment ( P ＜ 0.01 ). Conclusions Edaravone has favorable effects on cognition dysfunction in elderly patients with acute ischemic cerebral stroke ,which may be related to the regulation of the MAPK/ERK signaling pathway.

OBJECTIVETo initially explore the clinical effect of cool-tip radiofrequency ablation combined with enucleation for the giant hamartoma of kidney with narrow base and export-oriented way of growth.

METHODSThe clinical date of 15 patients including 6 male and 9 female with special hamartoma of kidney underwent cool-tip radiofrequency ablation assisted enucleation from July 2011 to October 2014 were reviewed.The median age was 49 years (ranging from 35 to 71 years). There were 6 cases with left renal tumor, 8 cases with right renal tumor and 1 case with solitary kidney tumor.All patients were confirmed by B ultrasound or CT scan, the mean diameter of hamartoma of kidney was 9.7 cm(8.5-12.7)cm, all tumors were located distant from the collecting system and presents with a special way of growth.The preoperative hemoglobin was (129±18)g/L, SCr was (92±41)μmol/L, glomerular filtration rate (GFR) was (32±12)ml·min(-1)·1.73 m(-2).

RESULTSCool-tip radiofrequency ablation assisted enucleation was technically successful in all patients.The mean operative duration was (115±31)minutes, and the average intraoperative bleeding was (72±21)ml with no blooding transfusion.The postoperative hospital stay was(7±2)days, and the postoperative hemoglobin was(129±18)g/L, SCr (92±41)μmol/L, GFR(30±15)ml·min(-1)·1.73 m(-2). No statistic change of hemoglobin and SCr or glomerular filtration rate after operations(all P>0.05). Postoperative pathology showed that all cases were hamartoma of kidney.During a mean follow-up period of 19.5 months, none of them had local tumor recurrence or chronic renal insufficiency.

CONCLUSIONSCool-tip radiofrequency ablation assisted enucleation is both safe and effective in the treatment of huge hamartoma of kidney with a narrow base and export-oriented way of growth. The short-term follow-up shows a satisfactory therapeutic effect.

Adult ; Aged ; Angiomyolipoma ; surgery ; Blood Transfusion ; Catheter Ablation ; methods ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Neoplasms ; surgery ; Length of Stay ; Lipoma ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Postoperative Period ; Treatment Outcome

Objective To elevate the efficacy and safety of low molecular weiGht heparins on severe acute pancreatitis. Methods Random or controlled clinical trials literatures( CRT,CTT ) which met the inclusion criteria were collected by computer retrieval combined with manual screeninG,and the data were analyzed by Meta-analysis. Results There were 6 randomized controlled study,includinG 626 cases severe acute pancreatitis which divided into low molecular weiGht heparin Group(n=3l2)and control Group(n=3l4). There were statistical siGnificant differences between Groups in terms of the mortality rate cure rate,complication rate, operation rate,averaGe hospitalization time( P<0. 05). while the parameters of coaGulation showed no siGnificant difference between two Groups. Conclusion Conventional treatment of SAP with LMWH is superior to conventional therapy in improvinG patients'outcome and decreasinG the mortality. Initial subcutaneous therapy with the LMWH appeared to be effective and safe,which cannot lead to bleedinG tendency.