Clinical efficacy and mechanism of action of kidney-tonifying, spleen-strengthening, and diuresis-promoting therapy in treatment of chronic hepatitis B / 临床肝胆病杂志

Chronic hepatitis B is a public health issue worldwide. Nucleotide analogues and interferon therapy can effectively inhibit HBV replication, but they still have the shortcomings such as inability to achieve the clearance of HBV cccDNA and low HBsAg clearance rate. The academic viewpoint of "kidney-tonifying therapy for chronic hepatitis B" provides new ideas and methods for the treatment of hepatitis B. During long-term clinical practice, Department of Hepatology in Shuguang Hospital has identified that "deficiency of spleen and kidney with damp heat remaining" is the key pathogenesis of the continuous progression of chronic hepatitis B and has established the treatment regimen for chronic hepatitis B with the basic treatment method of tonifying the kidney, strengthening the spleen, and promoting diuresis. The clinical research of National Science and Technology Major Project from The 11th Five Year Plan to The 13th Five Year Plan has validated the clinical efficacy of this regimen and clarified that regulating the immune function of the body is the main mechanism of the kidney-tonifying, spleen-strengthening, and diuresis-promoting therapy in the treatment of chronic hepatitis B.

Effect of naringenin on natural killer cell cytotoxicity against hepatocellular carcinoma cells in vitro and its mechanism / 临床肝胆病杂志

Objective To investigate the effect of naringenin on the killing rate of natural killer (NK) cells and related mechanism by amplification of human peripheral blood mononuclear cells into NK cells in vitro and co-culture with hepatocellular carcinoma (HCC) CLC5 cells at a ratio of 1∶ 1. Methods A lymphocyte separation medium was used to isolate human peripheral blood mononuclear cells, which were induced with recombinant human interleukin-2 in vitro to culture NK cells. CCK-8 assay was used to measure the proliferation of HCC cells after human HCC cells were treated with naringenin (0, 3.125, 6.25, 12.5, 25, and 50 μmol/L) for 0, 24, and 48 hours, and after human NK cells were treated with different concentrations of naringenin for 24 hours, CCK-8 assay was used to measure the proliferation of NK cells. CellTiter-LumiTM was used to measure the killing rate of NK cells after the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours. Quantitative real-time PCR was used to measure the gene expression of the activating receptor NKG2D in NK cells and NKG2D ligands in HCC cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results After being induced and cultured by recombinant human interleukin-2, NK cells were amplified to 82.33%±0.70% of human peripheral blood mononuclear cells. After naringenin treatment for 24 hours, there was no significant difference in the proliferation rate of HCC CLC5 cells between all mass concentration groups (all P > 0.05), and in the 25 and 50 μmol/L mass concentration groups, naringenin significantly promoted the proliferation of NK cells (both P 0.05); it significantly upregulated the expression of the NKG2D ligands such as ULBP1 and ULBP3 in HCC cells (all P < 0.001). Conclusion Naringenin may increase the killing activity of NK cells by upregulating the expression of NKG2D ligands in HCC cells.

Influence of virologic response on disease progression in patients with compensated hepatitis B cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of sustained virologic response on disease progression and the development of hepatocellular carcinoma (HCC) in patients with compensated hepatitis B cirrhosis receiving antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 542 patients with compensated hepatitis B cirrhosis who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 1 to December 31, 2013, received antiviral therapy, and were followed up for more than 5 years were enrolled, and according to the status of virologic response during follow-up, they were divided into a sustained virologic response cohort with 496 cases and a non-sustained virologic response cohort with 46 cases. With disease progression as the outcome event, general information and examination data were collected during the 5-year follow-up period. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed; relative risk and 95% confidence interval (CI) were used to investigate the degree of correlation of factors measured with the progression of liver cirrhosis. The life-table method was used to calculate the 1-, 3-, and 5-year progression-free survival rates, and the Kaplan-Meier method was used to plot survival curves; the log-rank test was used for univariate analysis, and the Cox regression model was used for multivariate regression analysis. ResultsFor the 542 patients, the mean progression-free survival time was 62.50 months (95% CI: 61.01-63.92), and the 1-, 3-, and 5-year progression-free survival rates were 94%, 82%, and 71%, respectively. The sustained virologic response cohort had a significantly longer mean progression-free survival time than the non-sustained virologic response cohort ［63.10 months (95% CI: 61.65-64.55) vs 55.95 months (95% CI: 50.19-61.71), χ2=12.058, P=0.001］. Compared with the non-sustained virologic response cohort, the sustained virologic response cohort had significantly lower 5-year cumulative incidence rate of HCC than (20.6% vs 34.8%, χ2=5.759, P=0.016) and 5-year cumulative incidence rate of decompensated cirrhosis (5.0% vs 15.2%, χ2=8.239, P=0.004). Virologic response was an independent risk factor for disease progression (hazard ratio=232, 95% CI: 1.45-3.72). ConclusionSustained virologic response can reduce the incidence rates of complications and HCC, improve long-term prognosis, and prolong survival time in patients with compensated hepatitis B cirrhosis.

Effect of molecular phenotype based on Warburg effect pathway on the prognosis and the efficacy of postoperative radiation in cervical cancer / 中华放射医学与防护杂志

Objective:To investigate the expression of Pyruvate dehydrogenase kinase 1(PDK1), phosphorylated Pyruvate dehydrogenase (p-PDH) and Pyruvate kinase isozyme type M2 (PKM2) based on Warburg effect pathway in cervical cancer tissues, and explore the roles of these molecules on prognosis and recurrence after postoperative radiation.Methods:The expressions of PDK1, p-PDH and PKM2 in primary tissues of 102 patients with cervical cancer were detected by immunohistochemistry, including 63 patients receiving postoperative radiation. The expression of the three molecules on prognosis and the efficacy of postoperative radiation on cervical cancer were analyzed separately and corporately.The level of mRNA were verified by using the 300 patients from GEO database. Kaplan-Meier method and COX proportional hazards regression model were used for univariate and multivariate analysis.Results:High expression of PDK1 and all the three indicators (PDK1 high/p-PDH high/PKM2 high) were positively correlated with pelvic lymphnode metastasis ( χ2=10.890, 7.407, P<0.05). PDK1 high/p-PDH high/PKM2 high, Federation International of Gynecology and Obstetrics (FIGO) staging, pelvic lymph node metastasis and postoperative radiation could affect the overall survival (OS) and disease-free survival (DFS) ( P<0.05). Multivariate analysis showed that PDK1 high /PDH high/PKM2 high, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS( P<0.05). The verification result of the GEO dataset showed that PDK1 high/PDH high/PKM2 high was the risk factor for DFS( P<0.05). Pathological type, pelvic lymph node metastasis and PDK1 high/p-PDH high/PKM2 high could affect the DFS of those patients with postoperative radiation ( P<0.05). In addition, the multivariate analysis showed that pathological type and PDK1 high /p-PDH high/PKM2 high were the independent prognosis factors for DFS( P<0.05). Conclusions:The patients of PDK1 high /p-PDH high/PKM2 high phenotype have poor prognosis and DFS with postoperative radiation, which may be a high-risk group with poor prognosis and high recurrence rate after postoperative radiotherapy of stageⅠ-Ⅱ B cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer.

Sequence analysis of the HBV S protein in patients with chronic hepatitis B / 中华检验医学杂志

Objective To analysis the frequency and mutational patterns of HBV(hepatitis B virus) S protein in the different phases of chronic hepatitis B patients, exploring the clinical implication of these mutations in CHB. Methods The difference of S protein mutation rates and mutation site among each groups were analyzed by cases-comparison. 112 cases of chronic hepatitis B patients in Shanghai Shu-guang hospital were enrolled in this study; they were divided into four groups, immune-tolerance group [IT, 36 cases, male 20 cases,female 16 cases,age 28.00 (25.00,30.75)years], immune-clearance group [IC, 28 cases, male 17 cases,female 11 cases,age 29.00 (25.25,31.75) years], low-replication group [LR, 25 cases, male 17 cases,female 8 cases,age 39.00 (35.00,45.50) years], reactivation group [RE, 23 cases, male 15 cases,female 8 cases, age 43.00 (36.00, 48.00) years]. DNA sequencing was used to detection HBV S protein gene mutation. Difference between categorical variables were analyzed using Chi-square test, Non-parametric test (kruskal-wallis H and Mann-Whitney U) was used for non-normal distribution data. Results Naturally occurring MHR (major hydrophilic region) variants was 16.67％ (6/36 cases) in IT group, preferentially within"a"determinant in the first loop, compared with IC (21.43％,6/28 cases), LR (20.00％,5/25 cases) and RE (34.78％,8/23 cases), there was no statistics Significance (χ2=2.814, P=0.421), while variant frequencies outside the MHR were 11.11％ (4/36 cases) and 14.29％ (4/28 cases) in IT and IC group, viral diversity gradually increased during LR phase with 24.00％(6/25 cases) of mutation frequency, and peak at RE phase (52.17％, 12/23 cases) with a statistics significance (χ2=15.041, P=0.002). Conclusion Amino acid substitutions is not only the consequence of the pressure of host immunity, it may be a probably cause of disease reactivation.

Analysis of the Related Risk Factors for Elevated ALT Level in Patients with Non-Alcoholic Fatty Liver Diseases / 现代检验医学杂志

Objective To analysis the risk factors for elevated ALT level in patients with Non-alcoholic fatty liver diseases (NAFLD).Method Fifty-six (male 25,female 31) NAFLD patients with elevated ALT and 153 NAFLD patients (male 64,female 89) with normal ALT and 160 (male 80,female 80) health subjects were selected.ALT was detected by rate assay,total cholesterol (TC),triglycerides (TG),low-density lipoprotein cholesterols (LDL-C),high-density cholesterol (HDL-C) and uric acid (UA) were detected by enzymatic method.Free fatty acid (FFA) was detected by immunoturbidimetry assay.Spearman correlation was used to analysis the relation between ALT and TC,TG,LDL-C,HDL-C,UA and FFA.Logistic regression was used to analyses the risk factor for elevated ALT level.Results TC,TG,LDL-C,UA and FFA levels were significantly higher in NAFLD group (including normal ALT group and elevated ALT group) than those in health group no matter male and female,HDL-C was significantly lower in these two groups when compared to control group,but binary logistic regression and spearman analysis showed that only UA and FFA were the risk factors for elevated ALT level and significantly positively correlated with ALT level,abnormal UA and FFA for male were associated with 3.96-fold(95CI％ =1.40～ 11.22,P=0.010) and 3.27-fold (95 ％ CI =1.14 ～ 9.40,P =0.028) of increased risk of elevated ALT level respectinely,correlation coefficient were 0.40(P=0.000),0.29(P=0.006),Meanwhile Exp(B) of elevated ALT level for female with abnormal UA,FFA were 4.49 (95CI％=1.79～11.28,P=0.001) and 3.17 (95CI％ =1.25～8.04,P=0.015),correlation coefficient were 0.34 (P =0.000),0.27 (P =0.003).Conclusion Elevated ALT level was not associated with dyslipidemias,but related to UA and FFA.They can be used as candidate markers for predicting severity of liver damage.

The study of peripheral blood miR-29a/101 in the diagnosis of Alzheimer's disease / 中华行为医学与脑科学杂志

Objective To detect the expressions of circulating microRNAs (miRNAs) of peripheral whole blood in Alzheimer's disease (AD) and investigate the potential roles of the miRNAs as diagnostic bi omarkers for Alzheimer's disease.Methods Peripheral blood samples were obtained from 110 AD patients and 150 age-and gender-matched normal controls.The concentrations of seven candidate miRNAs,including miR-9,miR-29a,miR-29b,miR-101,miR-181c,miR-137and miR-126,were measured with a real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method.The data of two groups were collected and analyzed by SPSS 19.0 software.Results It was found that miR-29a (P=1.12×10-5) and miR-101 (P=6.24× 10-7) were markedly down-regulated in peripheral blood of AD patients compared with normal controls.In addition,logistic regression analysis revealed peripheral whole blood miR-29a/101 combination could be a potential biomarker of AD with better specificity (82％) and sensitivity (75％).Conclusions miR-29a/101 combination in peripheral whole blood may serve as a useful noninvasive diagnostic biomarker for AD.

Role of follicular helper T cells in development and progression of liver diseases / 临床肝胆病杂志

Follicular helper T cell (TFH) is a new CD4+ T lymphocyte subset which helps B lymphocytes to produce antibodies and is closely related to the development and progression of liver diseases. This article reviews the detection and differentiation of TFH and related functional molecules, the mechanism of action of TFH in helping B lymphocytes to produce antibodies through producing interleukin-21, as well as the role of TFH in liver diseases such as chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis, primary biliary cirrhosis, hepatic failure, and liver transplantation, and points out that TFH may become the new target cell in the treatment of liver diseases.

Influence of interaction between endogenous miRNAs and hepatitis B virus in hepatocytes on hepatitis B virus transcription and related mechanisms / 临床肝胆病杂志

MicroRNAs (miRNAs) may be involved in the regulation of gene expression after transcription and play important roles in regulating hepatitis B virus (HBV) transcription and replication. This article summarizes the miRNAs with an anti-HBV effect in hepatocytes and 4 regulatory mechanisms, as well as the mechanisms through which HBV affects the expression of endogenous miRNAs in hepatocytes via HBx and self-coding miRNAs and promotes replication. The analyses show that the interaction between endogenous miRNAs and HBV in hepatocytes forms a complex regulatory network, competes for the results of regulation, and determines the activity of HBV transcription and the trend of disease progression. In-depth studies on the mechanisms of the influence of interaction between endogenous miRNA and HBV in hepatocytes on HBV transcription have great significance in exploring new anti-HBV methods.

Protein content of neuroglobin in rat brain with septic shock / 临床麻醉学杂志

Objective To observe the expression of neuroglobin in brain of rat with septic shock,and study the protective effect of neuroglobin.Methods Sixty male SD rats were randomly di-vided into two groups,30 rats in each.The rats in group M were injected LPS 10 mg/kg through tail vein to establish septic shock model,the success standard of septic shock was systolic blood pressure dropping to 60% of the basic values;the control group were given equal volume of NS.The levels of rat TNF-α,IL-6 and NGB in serum at the time points of before LPS injection (T0 ),1 h (T1 ),2 h (T2 ),4 h (T3 )and 6 h(T4 )after LPS injection were measured using ELISA kits.NGB and caspase-3 protein expression in brain were determined using Western blotting.Results Compared with group C and T0 ,the TNF-α,IL-6 concentrations in serum and caspase-3 in brain were increased significantly at T1-T4 (P <0.05),NGB protein content in serum and brain at T3 and T4 were increased significantly (P <0.05).Conclusion Cell apoptosis and inflammatory response are discovered in the brain during septic shock.NGB is over-expressed in brain of rats with septic shock,which may play a role of pro-tective function.

A randomized controlled clinical trial of the effectiveness and safety between aspherical and NUV soft hydrophilic contact lenses for myopia patients / 中华实验眼科杂志

Background The clinical effectiveness of soft corneal contact lens for correction of myopia has been confirmed.Theoretically,aspherical soft hydrophilic corneal contact lens has better visual qualify for myopic eyes,and the lenses have been applied widely.But abnormal tear film,even many cornea and conjuctiva diseases caused by soft contact lens have been reported,so the effectiveness and safety of aspherical soft hydrophilic corneal contact lens are worth concerning.Objective This clinical trail was to compare the effectiveness and safety between aspherical and NUV soft hydrophilic contact lens for myopic eyes.Methods A randomized,double-blind and controlled clinical study was performed under the approval of Ethic Committee of Qingdao Municipal Hospital and informed consent of each patient.One hundred and forty eyes of 70 myopic patients were enrolled in QingdaoMunicipal Hospital from July to October,2012.The subjects were randomized into the trial group and control group using random number table.Aspherical soft hydrophilic contact lenses were worn in the trial group and NUV soft hydrophilic contact lenses were worn in the control group.The characteristics of the lens surface,outcomes and the eye number in different scores of ocular signs and symptoms were assessed before and 15 minutes,1 week,2 weeks and 1 month after wearing lenses.Results The sores of humidity of anterior surface,the sediment in anterior and posterior surface are 0 in both lenses in various time points after wearing.The corrected visual acuity of all the subjects were ≥ 1.0.The eye number of 2-3 scores in various ocular signs was 0 in both groups,but the eye number of 1 score in palpebral conjunctival congestion and limbus congestion were more in the trail group than those in the control group in different time points (all at P＜0.05).There were significant differences in corneal fluorescine staining between the groups in different time points (all at P＞0.05).There was no eye for 2-3 scores of eye symptoms in both groups.The eye number for 1 score in foreign body sensation increased in the target-trail group compared to the control group at various time points (P =0.002,0.006,0.005,0.005).However,there was no statistically significant differences in the eye number for 1 score in visual clearness and stability between the two groups at the follow-up duration (all at P＞ 0.05).Conclusions Aspherical soft hydrophilic corneal contact lens has good outcomes in corrected visual acuity for myopia like NUV soft hydrophilic contact lens,but the wearing of aspherical soft hydrophilic corneal contact lens induces more ocular discomfortableness.

Therapeutic Observation of Auricular Point Sticking with Magnetic Bead for Insomnia in Hepatocirrhosis / 上海针灸杂志

Objective To observe the clinical efficacy of auricular point sticking with magnetic bead in treating insomnia in hepatocirrhosis patients. Method Ninety patients with hepatocirrhosis complicated with insomnia were randomized into a treatment group and a control group, 45 in each group. The treatment group was intervened by auricular point sticking with magnetic bead, while the control group was by auricular point sticking with medical adhesive tape. After successive 2-week treatments, the Insomnia Severity Index (ISI) and the Evaluation Criteria of Therapeutic Efficacy for Mental Disorders were observed for evaluating the treatment result. Result The ISI was significantly improved in the treatment group after intervention (P<0.05), and the improvement was significantly different from that in the control group (P<0.05). The total effective rate was 86.7% in the treatment group versus 60.0% in the control group, and the difference was statistically significant (P<0.01). Conclusion Auricular point sticking with magnetic bead is easy-to-operate and can produce a satisfactory efficacy in treating insomnia of hepatocirrhosis patients.

Association between CISH polymorphisms and susceptibility to chronic hepatitis B in Chinese Han population / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association between rs414171 single nucleotide polymorphisms (SNP) of cytokine- inducible src homology 2 domain protein (CISH) and the susceptibility to chronic hepatitis B.</p><p><b>METHODS</b>A total of 233 Chinese Han patients with chronic hepatitis B and 148 age- and sex-matched healthy controls were enrolled in this case-control study. The SNP rs414171 was genotyped by Sequenom MassArray-IPLEX to analyze the relationship between rs414171 and chronic hepatitis B.</p><p><b>RESULTS</b>The distribution of SNP rs414171 allele and genotype frequencies showed no significant difference between the patients and healthy controls (P>0.05).</p><p><b>CONCLUSION</b>CISH rs414171 is not significantly associated with the susceptibility to chronic hepatitis B in Chinese Han population.</p>

Trabeculectomy with adjustable sutures on the ocular function score in patients with angle-closure glaucoma / 中国基层医药

Objective To study trabeculectomy with adjustable sutures on the ocular function score in pa-tients with angle-closure glaucoma .Methods 98 cases ( 134 eyes ) were randomly divided into the two groups , the control group(n=49 cases,66 eyes) and the observation group (n=49 cases,68 eyes).The patients in the control group were operated through trabeculectomy ,while the patients in the observation group were operated through trabe-culectomy with adjustable sutures .The occurrence of the two groups of patients intraocular pressure changes , and recovery of sight,shallow anterior chamber before and after surgery three months were observed .Postoperative 1d,3d, 1m and 3m ocular function score were compared .Results Postoperative 3 months IOP were significantly lower ( t=3.921,5.746,all P<0.01),and compared with the control group ,the observation group significantly decreased (t=2.680,P<0.05).Postoperative 3 months visual acuity significantly improved in patients (t=2.460,2.976,all P<0.05),and compared with the control group,the observation group improved more significantly (t =2.062,P <0.05).The incidence of postoperative shallow anterior chamber were 12.1% in the control group and 2.9% in the observation group Shallow anterior chamber in observation group was significantly less than that in the control group (χ2 =7.98,P<0.01).The two groups of patients after ocular surface scores were decreased in the observation group after 1d,3d,1m and 3m and ocular scores were lower than that of the control group ( t =2.1901,2.680,3.172, 3.013,all P<0.05).Conclusion Trabeculectomy with adjustable sutures can promote the recovery of angle-closure glaucoma,ocular function.

Observation on Manifestations of Tongue .and Gastric Musosa in Rats with Experimental Precancerous Lesion of Gastric Mucosa / 中医杂志

Healthy male Wistar rats were prepared as model of precancerous lesion of gastric mucosa. The tongue, pH of tongue surface, dropped cells from tongue fur, histology of tongue. and corresponding gastric mucosa, pH of gastric juice, mucosal histological changes in both groups were observed. Results revealed that, in the rats with precancerous lesion, the tongues were bare or only with little fur, dark purplish tongue with petechia. pH of both tongue and gastric juice were high, which were both coincided with the syndrome type of asthenic gastric - qi and blockage of collaterals by stagnant blood.