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Primary biliary cholangitis (PBC) is an autoimmune disease commonly observed in middle-aged women, and it may progress to liver cirrhosis and liver failure. Ursodeoxycholic acid and obeticholic acid are the only first - and second-line drugs approved by the FDA, but about 40% of patients are insensitive to UDCA. Studies are being conducted on a variety of second-line drugs such as fibrates and immunosuppressive drugs, and liver transplantation is the only treatment method for end-stage PBC. This article reviews the research advances in the treatment of PBC and related mechanisms, in order to provide a reference for clinical practice.
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Objective:To explore whether microRNA (miRNA) -181b-5p inhibits the proliferation and invasion of cutaneous melanoma cells by targeting pleckstrin (PLEK) .Methods:Bioinformatics methods were used to analyze cutaneous melanoma-associated core genes; dual-luciferase reporter assay was performed to verify the targeted interaction between miRNA-181b-5p and PLEK. Oligo RNA and small interfering RNA (siRNA) were used to regulate the expression of miRNA-181b-5p and PLEK in A375 cells respectively in this experiment, and A375 cells were divided into the following groups in detail: mimic negative control group, miRNA-181b-5p mimic group, inhibitor negative control group, miRNA-181b-5p inhibitor group, PLEK siRNA group, siRNA negative control group, miRNA-181b-5p inhibitor + control siRNA co-transfection group and miRNA-181b-5p inhibitor + PLEK siRNA3 co-transfection group. After 48-hour treatment, qPCR was performed to determine the mRNA expression of miRNA-181b-5p and PLEK in A375 cells, Western blot analysis to determine the PLEK protein expression, and Transwell assay to assess the invasive ability of A375 cells; after additional 24-96 hours of culture, cell counting kit-8 (CCK8) assay was conducted to assess the proliferative ability of A375 cells.Results:PLEK was the core gene for cutaneous melanoma. PLEK expression in the cutaneous melanoma in situ tissues was significantly higher than that in the paracancerous tissues ( P = 0.031) , but lower than that in the metastatic tissues ( P = 0.001) . Compared with human epidermal melanocytes HEMa-LP, the mRNA and protein expression of PLEK significantly increased in A375 cells (mRNA: 3.884 ± 0.156 vs. 0.997 ± 0.010, t = 18.48, P < 0.001; protein: 2.840 ± 0.301 vs. 1.029 ± 0.094, t = 5.47, P = 0.005) , but the miRNA-181b-5p expression significantly decreased in A375 cells (0.333 ± 0.042 vs. 0.967 ± 0.069, t = 7.83, P = 0.001) . Dual-luciferase reporter assay showed targeted binding of miRNA-181b-5p to PLEK. Compared with the mimic negative control group, the miRNA-181b-5p mimic group showed significantly decreased survival rate of A375 cells (48 hours: t = 7.96, P = 0.015; 72 hours: t = 7.50, P = 0.002; 96 hours: t = 7.96, P = 0.001) , and significantly decreased invasive ability of A375 cells ( t = 5.07, P = 0.007) ; on the contrary, the survival rate and invasive ability of A375 cells were significantly higher in the miRNA-181b-5p inhibitor group than in the inhibitor negative control group (survival rate: 24 hours, t =5.38, P = 0.013; 48 hours, t = 5.36, P = 0.013; 72 hours, t =7.63, P = 0.005; 96 hours, t = 5.99, P = 0.004; invasive ability: t = 7.24, P = 0.002) ; compared with the siRNA negative control group, the proliferative and invasive ability of A375 cells significantly decreased in the PLEK siRNA group (proliferative ability: 48, 72, 96 hours, P = 0.015, 0.011, 0.001, respectively; invasive ability: t = 4.93, P = 0.008) ; compared with the miRNA-181b-5p inhibitor + control siRNA co-transfection group, the miRNA-181b-5p inhibitor + PLEK siRNA co-transfection group showed significantly decreased proliferation rate and invasive ability of A375 cells (proliferation rate: 24, 48, 72, 96 hours, P = 0.042, 0.042, 0.037, 0.017, respectively; invasive ability: t = 8.52, P = 0.001) . Conclusion:miRNA-181b-5p can inhibit the proliferation and invasion of cutaneous melanoma A375 cells, likely by down-regulating the PLEK expression.
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Objective To investigate the relationship between the severity of white matter lesions (WMLs) and the hematoma volume in patients with spontaneous intracerebral hemorrhage. Methods Patients with intracerebral hemorrhage (age ≥40 years) who were included in the Image Registration Center, Drum Tower Hospital, Nanjing University School of medicine from June 1, 2012 to May 31, 2017 were enrolled retrospectively. The head CT and baseline head MRI data were collected within 12 h after onset. The volume of hematoma on the baseline CT was calculated using ITK-SNAP software. The WMLs volume was semi-automatically segmented and calculated in the WMLs area by MRIcron software and ITK-SNAP software. According to the Fazekas score, the severity of WMLs was divided into mild ( 0-2), moderate (3-4) and severe (5-6). According to the median volume of hematoma, the patients were divided into smaller hematoma volume group and larger hematoma volume group. The baseline data in patients of both groups were compared. Multivariate logistic regression analysis was used to determine the independent related factors of hematoma volume. Results Age, National Institutes of Health Stroke Scale (NIHSS) score, and hematoma volume increased with the severity of WMLs, while the total cholesterol and low-density lipoprotein cholesterol levels decreased with the severity of WMLs. Hematoma volume was significantly associated with the NIHSS scores, apolipoprotein A1, D-dimer, WML volume, and intracerebral hemorrhage site. Multivariate logistic regression analysis showed that high WML score (odds ratio [OR] 1.001, 95% confidence interval [ CI] 1.002-1.008; P=0.049), intracerebral hemorrhage site ( OR 1.441, 95% CI 1.090-1.911; P=0.010), and NIHSS score (OR 1.081, 95% CI 1.011-1.152; P=0.031) were the independent risk factors for larger hematoma volume. Conclusion The severity of WMLs was significantly positively correlated with the baseline hematoma volume in patients with spontaneous intracerebral hemorrhage.
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Objective@#To investigate the impact of gender and age on in-hospital major adverse cardiovascular and cerebrovascular events of patients with acute ST-segment elevation myocardial infarction (STEMI).@*Methods@#This is a retrospective single-center study. A total of consecutive 1 102 patients with acute STEMI admitted to our hospital from January 2001 to December 2010 were recruited and clinical data were analyzed. The primary end point was in-hospital death due to any cause, and the secondary end point was in-hospital composite end point including death, re-infarction and stroke. Multivariate logistic regression analyses were performed to identify the risk factors of in hospital death and composite end point.@*Results@#The study population included 283(25.7%(283/1 102)) female patients and female patients were older than male patients ((68.7±11.2)years vs. (59.2±12.5)years, P<0.001). Compared with male patients, less female patients received primary percutaneous coronary intervention (50.9%(144/283) vs. 70.9%(581/819), P<0.001), had higher rates of in hospital death(10.6%(30/283)vs. 6.0%(36/819), P<0.001) and composite endpoint(14.1%(40/283)vs. 7.0%(57/819), P<0.001). Among STEMI patients aged <60 years, no differences were found in in-hospital mortality (1.7%(1/58)vs. 1.4%(6/437)) and composite endpoint(3.6%(3/58)vs. 3.4%(15/437)) rates between female and male patients (both P>0.05). Among STEMI patients aged ≥60 years, female patients had higher in-hospital mortality (12.9%(29/225)vs. 7.9%(30/382), P<0.001), and there was no difference on composite endpoint between female and male patients (16.4%(37/225)vs. 11.0%(42/382), P=0.054). Multivariate logistic regression analysis showed that female gender was not the independent risk factor of in-hospital death(OR=1.029, 95%CI 0.564-1.877, P=0.926) and composite end point(OR=1.593, 95%CI 0.989-2.566, P=0.055), but age was the independent risk factor of in-hospital death(OR=1.065, 95%CI 1.037-1.094, P<0.001) and composite end point(OR=1.050, 95%CI 1.029-1.071, P<0.001)in STEMI patients. Multivariate logistic regression analysis also showed that female was not the independent risk factor of in-hospital death(OR=1.539, 95%CI 0.572-4.142, P=0.394) and composite end point(OR=1.563, 95%CI 0.689-3.546, P=0.285), but age was the independent risk factor of in-hospital death(OR=1.052, 95%CI 1.011-1.096, P=0.013) and composite end point(OR=1.042, 95%CI 1.008-1.077, P=0.016)in STEMI patients received primary percutaneous coronary intervention.@*Conclusion@#Female patients with STEMI have higher incidence of in-hospital major adverse cardiovascular and cerebrovascular events than male patients, and age is the independent risk factor of in-hospital major adverse cardiovascular and cerebrovascular events of STEMI patients.
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Objective To explore the long-term compliance of continuous positive airway pressure ventilation in patients with obstructive sleep apnea hypopnea syndrome.Methods The clinical data of 62 patients with obstructive sleep apnea hypopnea syndrome were retrospectively analyzed. According to the patients'compliance of continuous positive airway pressure ventilation in 12 months,the patients were divided into 2 groups: good compliance group (34 cases) and poor compliance group (28 cases).The cause of poor compliance and the long-term risk factors of poor compliance with continuous positive airway pressure ventilation in patients with persistent positive airway pressure were analyzed. Results In 28 cases of poor compliance,the main reasons were inadaptation machine during pressure titration of continuous positive pressure ventilation(9 cases),complex operations(6 cases)and unwanted complex treatment(4 cases).The Logistic multiplicity analysis result showed that male(OR=1.737,95% CI 2.397-4.184),rural residence(OR=3.522,95% CI 2.025-3.987),low educational level(OR=3.673,95% CI 2.017-4.812),short time flow monitoring(OR=2.301,95% CI 2.485-4.128),short pressure titration time (OR = 2.012,95% CI 2.783 - 3.573) and many times pressure titration (OR =1.993, 95% CI 2.593 - 3.717) were the independent risk factors of poor compliance of continuous positive airway pressure ventilation in patients with obstructive sleep apnea hypopnea syndrome(P<0.05 or<0.01).Conclusions The long term compliance of continuous positive airway pressure ventilation in patients with obstructive sleep apnea hypopnea syndrome is poor. Health education should be strengthened in patients of male,rural residence,low educational level,short time flow monitoring,short pressure titration time and many times pressure titration,in order to improve the treatment compliance.
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Objective To understand the management status quo of migrant workers with chronic hepatitis B (CHB) to ex‐plore the management countermeasures and improve the survival quality for tamping the foundation of the healthy project .Methods Totally 300 migrant workers with CHB were performed the living quality evaluation and investigation on the service needs ,com‐pliance ,economic condition ,categories and proportion of reimbursement by adopting the supplementary revision of SF‐36 living quality scale and general information questionnaire ;the influencing factors of their living quality were performed the univariate anal‐ysis and multivariate stepwise regression analysis .Results The statistical analysis found that whether convenient for outside visit‐ing hospital ,categories and proportion of reimbursement ,whether normalized antiviral therapy ,whether conducting examination and follow up at regular intervals and liver disease specific symptoms were the influencing factors of living quality in the migrant work‐ers with CHB(P<0 .05);the living quality in the patients with outside convenient visiting hospital ,high reimbursement proportion , normalized antiviral therapy and examination and follow up at regular intervals was significantly higher than that in the patients with inconvenient outside visiting hospital ,low reimbursement proportion ,non‐normalized anti‐viral therapy and examination and follow up without regular intervals(P<0 .05);the liver disease specific symptom score showed the positive correlation trend with the living quality score (B=7 .657 ,SD=2 .650 ,t=2 .889 ,P=0 .004) .Conclusion It is necessary to improve the patient′s medical needs ,reimbursement type and proportion ,increase the compliance of patient′s normalized examination and follow‐up at regular in‐tervals and standard antiviral treatment ,thus to realize the standardized examination and treatment in CHB patients ,prevent or de‐lay the disease progression ,avoid liver cirrhosis and decompensated hepatopathy ,reduce the occurrence of HCC ,improve the quality of life and prolong the survival period .
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BACKGROUND:Due to limitations of the physicochemical properties of soft denture liner material itself, whisker has been added in the soft lining material in recent years, so as to enhance its mechanical properties. OBJECTIVE:To investigate the effect of different additive amount of anhydrous calcium sulfate whisker on the mechanical function of self-curing soft denture liner. METHODS: There were six groups in this experiment. Anhydrous calcium sulfate whisker at the mass fraction of 0 (control), 1%, 2%, 3%, 4%, 5% was respectively added into self-curing soft liner materials, 10 test specimens in each group, a total of 60 test specimens. The shear bond strength, Shore hardness and tensile strength were detected. RESULTS AND CONCLUSION: With the increasing amount of the anhydrous calcium sulfate whisker, the Shore hardness of the soft lining material was increased continuously, and the tensile strength was increased firstly and then reduced. When 3% anhydrous calcium sulfate whisker was added, the bond strength and tensile strength of soft lining material reached the peak. Taken together, the mechanical properties of the soft lining materials became perfect when 3% anhydrous calcium sulfate whisker was added. These results demonstrate that anhydrous calcium sulfate whisker may affect the mechanical properties of self-curing soft liner.
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Objective To study the correlation between prognosis of non-small cell lung cancer ( NSCLC) patient and serum levels of HGF and IL-6. Methods Eligible 109 NSCLC patients and preoperative blood samples of each patient in our hospital from March 2013 to May 2014 were collected. Then the levels of HGF and IL-6 of serum samples were detected by using ELISA kit. All patients were followed up for 1 year. The neoplasm staging:67 cases were stagingⅠ-Ⅱ,38 cases were stagingⅢ,2 cases were staging IV. There were 79 cases with ad-enomatous carcinoma( ADC) ,26 cases with squamous carcinoma( SCC) and 4 cases with NSCLC. According to the TNM staging,there were 79 cases in pN( -) group,31 in pN( +) group,77 in pT(T1-T2) group and 28 in pT(T3-T4) group. Results The average concentration of HGF and IL-6 in serum were 860 pg/mL and 2. 7 pg/mL respectively. Analysis of survival indicated that,compared to those patient with lower serum level of HGF and IL-6,the survival rate of patient with high serum level was much lower. The difference was statistically signifi-cant (HGF,P=0. 019;IL-6,P=0. 002). The analysis of the patients with stageⅢdisease separately also indicated that survival rate of pa-tient with lower serum of HGF and IL-6 was higher than others. Conclusion The serum levels of HGF and IL-6 might be a effective indica-tors for predicting prognosis of the NSCLC paitents.
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BACKGROUND:Microleakage between restoration, tooth structure and bonding agent can cause the entry of bacteria and liquid in the mouth into the gap, thereby damaging the bonding interface between the restoration and tooth tissues, and leading to bond failure. Microleakage detection can directly show whether the closure of the root canal of post and core system is good or bad. The severity of microleakage directly affects the restorative effects of post and core. OBJECTIVE: To evaluate the effects of different root canal cleaning methods on the microleakage between the fiber post and root canal dentin. METHODS: Thirty fresh non-caries premolar posts with free root canalin vitro were randomly divided into five groups, and the root canal wal was respectively washed with saline, 5.25% sodium hypochlorite solution+17% ethylenediamine tetra-acetic acid (EDTA)+saline, 3% hydrogen peroxide solution+5.25% sodium hypochlorite+ saline, 3% hydrogen peroxide solution+2% chlorhexidine solution+saline, and 2% chlorhexidine solution+17% EDTA+saline in different groups. Super-bond C&B adhesive agent was used for bonding fiber post, and the microleakage of each sample was observed under stereomicroscope. RESULTS AND CONCLUSION: The severity of microleakage in the al groups was ranged as folows: saline group > 3% hydrogen peroxide solution+5.25% sodium hypochlorite+saline group > 5.25% sodium hypochlorite solution+17% EDTA+saline and 3% hydrogen peroxide solution+2% chlorhexidine solution+saline groups > 2% chlorhexidine solution+17% EDTA+saline group.
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BACKGROUND:At present, there are stil differences in the studies of total-etch, self-etch and self-bonding resin cement effect on the coronal microleakage and bonding strength of fiber posts. OBJECTIVE:To evaluate the coronal microleakage and the bonding strength of fiber posts treated with three kinds of resin cements. METHODS:Total y 32 upper incisors were randomly divided into five groups, including three experimental groups and two control groups. After the root canal preparation, three kinds of resin cements (EMBRACE WetBond, LuxaCore, Medental Multi-cure) were used to fiber posts with the bond diameter of 1.4 mm. Stereomicroscope was used to observe the microleakage. Then, the specimens were cut into 2 mm wafer along the axis of tooth, and universal testing machine for push-out test was used to observe the failure mode. In the positive control group, no root canal preparation was done, the root was coated with nail polish, and the crown was directly exposed to the dye. In the negative control group, no root canal preparation was done, the root canal orifice was covered with the resin, the tooth was overal coated with nail polish and then embedded 1 mm below the section. RESULTS AND CONCLUSION:The microleakage was observed in al the three resin cements, Medental Multi-cure showed the least microleakage and LuxaCore showed the largest microleakage, and there was significantly different among the three kinds of resin cements (P<0.05). The bonding strength of three cements had significant differences (P<0.05), and ranked from high to low:Mdental Multi-cure, LuxaCore, and EMBRACE WetBond. The main fracture modes were binder/fiber post fracture and mixed failure. The results suggest that the total-etch resin cement binds tightly with the dentin, and owns a superiority in the microleakage and bonding property as compared with the self-etch resin cements and self-bonding resin cements.
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BACKGROUND:Studies have confirmed that the surface treatment methods such as silane coupling agent and sand blasting could improve bonding strength of zirconia ceramics and resin binder. In addition, the increase of micro cracks on the surface of zirconia ceramics can also improve the bonding strength of zirconia ceramics and resin binder. But there is a lack of related studies addressing whether repeatedly sintering would have an impact on shear bond strength of zirconia ceramics. OBJECTIVE:To determine the effect of decorative porcelain temperature firing on the shear bond strength between dental zirconia ceramics and resin binder. METHODS:Twenty pieces of zirconia ceramics specimens were selected from 40 tablets, and then randomly divided into five groups according to the number of sintered times:control group (without sintering), sintering groups for 2, 4, 6, 8 times. Heat starting temperature was 500 ℃, and final temperature was 1 000 ℃ with a heating rate of 55 ℃/min. The vacuum time was 7 minutes. During the sintering, the final temperature was constant. Unsintered ceramic pieces were bonded using resin binder. Universal testing machine was used to test the shear strength of the interface between the two pieces of zirconia ceramics. The interface after shearing was characterized by scanning electron microscope. RESULTS AND CONCLUSION:The shear strength of sintering groups for 4, 6, 8 times was significantly higher than that of the control group (P0.05). Shear strength of specimens sintered 8 times was slightly higher than that sintered 4 and 6 times (P<0.05). Under the scanning electron microscope, there was no crack on the surface of non-sintered zirconia ceramics. After 2 times sintering, the surface appeared to have fine cracks. After sintering 4 times, visible cracks were increased. After six rounds of sintering, the surface began to have significant changes;cracks rose along with slight gaps and a smal amount of adhesive residues were found. After sintering for 8 times, cracks and voids were obviously increased on the sintered surface and adhesive residues were found. It indicated that after sintering for 4, 6 and 8 times, zirconia ceramics could have a good shear strength binding to resin adhesives;with the increasing of sintering times, the shear bond strength could be increased.
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ObjectiveTo explore the effect of simvastatin on the level of serum adiponectin and asymmetric dimethylarginine (ADMA) in patients with acute stroke.MethodsNinety patients with acute stroke were selected and divided by random digits table method into common treatment group and intervention treatment group with 45 cases each.The volume of cerebral infarction and the evaluation score of clinical neurological impairment degree were calculated.The levels of serum adiponectin and ADMA before and after treatment were detected by erzyme-linked immunosorbent assay.The changes of serum adiponectin and ADMA before and after treatment in two groups were compared and their correlations with the volume of cerebral infarction and the evaluation score of clinical neurological impairment degree were analyzed.Results The level of serum adiponectin and ADMA in two groups before treatment had no statistical differences (P ＞ 0.05 ).The levels of serum adiponectin in two groups after treatment increased and ADMA decreased significantly,which had significant differences compared with those before treatment ( P ＜ 0.05 ).The level ofserum adiponectin in intervention treatment group was significantly higher than that in common treatment group and ADMA was obviously lower than that in common treatment group after treatment [(5.92 ± 0.15)mg/L vs.( 4.51 ± 0.13 ) mg/L,( 0.96 ± 0.13 ) μ mol/L vs.( 1.08 ± 0.15 ) μ mol/L ] ( P ＜ 0.05 ).Rank correlation analysis showed that the level of serum adiponectin before treatment was negatively correlated with the volume of cerebral infarction and the evaluation score of clinical neurological impairment degree ( r ＝ -0.75,-0.59,P ＜ 0.05).The level of ADMA before treatment was positively correlated with the volume of cerebral infarction and the evaluation score of clinical neurological impairment degree ( r =0.68,0.71,P ＜ 0.05 ).Conclusion Simvastatin can increase the level of serurm adiponectin and decrease the level of ADMA efficiently in patients with acute stroke,and improve the prognosis of the patients.
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AIM: To explore the neuroprotective action of progesterone(PROG), which has been proved to be a "neuroactive steroid". METHODS: The model of focal cerebral ischemia was established in rats by reverserble inserting a nylon thread with a diameter of 0.2 mm into the anterior cerebral artery through the internal carotid artery. The effect of PROG was assessed by determining water,sodium, potassium, and calcium contents in striatum of rats subjected to 2 h ischemia followed by 22 h reperfusion. RESULTS: The water,sodium,and calcium contents of middle cerebral artery occlusion(MCAO) striatum were obviously higher,the potassium content was obviously lower than those of non-MCAO striatum in I/R and DMSO groups,but there was no significant difference between these two groups.Compared with the result in I/R and DMSO groups , water, sodium and calcium contents significantly decreased, but potassium(P0.05). CONCLUSION: Treatment with PROG can significantly reduce the striatal injury of rats with cerebral ischmia-reperfusion.
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AIM: To observe the protective effect of composite salviae dropping pills against human umbilical vein endothelial cells(HUVECs) injure induced by hydrogen dioxide(H_2O_2) and discuss the mechanism of its therapeutic action on cardiac and encephalic diseases.METHODS: HUVECs were injured by 0.1 mmol/L H_2O_2 and then different final concentrations of composite salviae dropping pills(0.5 g/L,0.25 g/L,0.1 g/L) were added before and after the injury.Cell viability was measured by MTT assay.TBA method was used to detect the intracellular malonaldehyde. Nitric oxide(NO) in the culture medium was detected by using nitrate reductase assay,and immunocytochemisty was used to observe the expression of NOS2,NOS3 and NF-?B.Morphologic observation was also performed.RESULTS: HUVECs were injured by 0.1 mmol/L H_2O_2.Composite salviae dropping pills increased the cell viability apparently,inhibited the production of MDA induced by H_2O_2,regulated the generation of NO bilaterally and influenced the expression of NOS3 and NF-?B.CONCLUSIONS: Composite salviae dropping pills at concentrations of 0.5 g/L,0.25 g/L and 0.1 g/L protects HUVECs from injury by H_2O_2,no matter it is be added before or affter the injury.The possible mechanism is associated with its regulating the expression of NOS2,NOS3 and NF-?B.
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AIM: To observe the function and morphological change of human umbilical vein endothelial cells(HUVECs) treated with lipopolysaccharide(LPS) and composite salviae dropping pills(DSP).METHODS: HUVECs were cultured and incubated within 10 mg/L LPS for 12 hours.Different final concentrations of composite salviae dropping pills(1 g/L,0.5 g/L,0.25 g/L,0.1 g/L) were added before and after LPS treatment. Cell viability,NO,NOS,ET-1 and intracellular calcium were measured.The cells were observed under inverted microscope,inverted phase contrast microscope,laser confocal scanning microscopy and transmission electron microscope.RESULTS: When given after LPS treatment,different final concentrations of composite salviae dropping pills played a protective role(P0.05).The HUVECs injured by LPS underwent apparent morphological change after treatment with composite salviae dropping pills.CONCLUSION: Composite salviae dropping pills have an evident protective effect on human umbilical vein endothelial cells exposed to LPS.