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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.
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ObjectiveTo investigate the effect of Zhizi Dahuang decoction （ZZDHT） in the treatment of alcoholic liver disease （ALD） by improving oxidative stress in hepatic neutrophils. MethodsNetwork pharmacology was used to obtain the chemical components of ZZDHT and their corresponding action targets and analyze the potential targets and functional pathways of ZZDHT in the treatment of ALD. The non-target metabolomics technology was used to observe the changes in the metabolites of ZZDHT in mouse serum and liver. The mice were given ZZDHT at a dose twice as much as the middle dose concentration by gavage， and serum and liver samples were collected at six time points after gavage （10 minutes， 30 minutes， 1 hour， 2 hours， 4 hours， and 6 hours） and were then mixed for mass spectrometry （administration group with 18 mice）， while the 18 mice in the control group were given an equal volume of normal saline by gavage. Ultra-performance liquid chromatography was used for rapid isolation and identification of the metabolites of ZZDHT in serum and liver tissue， and the effective constituents of ZZDHT were validated. Male C57BL/6J mice， aged 8 weeks， were randomly and equally divided into control group， model group， and low-， middle-， and high-dose ZZDHT groups， with 10 mice in each group. All mice except those in the control group were used to establish a mouse model of ALD （NIAAA model mice）， and at the same time， the mice in the administration groups were given low-， middle-， and high-dose ZZDHT by gavage， while those in the control group and the model group were given an equal volume of normal saline by gavage. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） were measured； PCR was used to measure the gene expression levels of related inflammation， oxidative stress， and neutrophil indicators in the liver； ELISA was used to measure the levels of related inflammation and oxidative stress indicators in serum； superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured to observe the level of oxidative stress in the liver； HE staining， myeloperoxidase staining， and oil red staining were used to observe liver injury， neutrophil infiltration， and lipid deposition. 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. ResultsA total of 53 active components and 227 target genes were obtained for ZZDHT， and there were 8685 target genes of ALD， resulting in 222 common target genes between these two groups of genes. Core pathways included the interleukin-6 signaling pathway and the TNF signaling pathway. The non-targeted metabolic analysis of ZZDHT obtained 225 metabolites in mouse liver and 227 metabolites in serum， among which there were 126 common metabolites. The core pathways of liver metabolites included glycerolipid metabolism and inflammatory mediator regulation of TRP channels， and the core pathways of serum metabolites included the AMPK signaling pathway and oxidative phosphorylation， all of which were associated with oxidative stress- and inflammation-related pathways. Compared with the model group， the low-， middle-， and high-dose ZZDHT groups had significant reductions in the serum levels of ALT， AST， and TG （all P<0.05）， and the middle-dose ZZDHT group had significant reductions in the levels of Ly6g， Ncf1， Ncf2， IL-6， TNF-α， IL-1β， MDA， 4-HNE， Gp91， and P22 in the liver （all P<0.05）， a significant increase in the level of SOD （P<0.05）， a significant reduction in the serum level of 4-HNE （P<0.05）， and a significant increase in the level of GSH-Px （P<0.05）. There were significant improvements in fat deposition and neutrophil infiltration in the liver of mice in the middle-dose ZZDHT group （both P<0.05）. ConclusionZZDHT significantly reduces oxidative stress and inflammatory response in NIAAA model mice.
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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.
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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=232, 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.
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Nonalcoholic fatty liver disease has become the most important chronic liver disease in China and the leading cause of abnormal liver biochemical parameters in physical examination. Mitophagy can degrade the mitochondria with impaired function and misfolded protein in the liver to regulate cell death and help to maintain stable lipid metabolism in the liver. The binding of adiponectin secreted by adipose tissue to adiponectin receptor 2 can increase the secretion of autophagy agonists in Kupffer cells, induce hepatocyte mitophagy, promote lipid metabolism, and thus reduce liver inflammation, which provides new thoughts for the research and development of drugs with a marked clinical effect and a clear mechanism of action in the treatment of nonalcoholic fatty liver disease.
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Portal hypertension refers to a series of clinical manifestations caused by elevated pressure of the portal vein system, which can cause portal hypertension by causing portal venous obstruction and / or increased blood flow. A typical clinical manifestation in patients with decompensated cirrhosis is portal hypertension. A severe complication of portal hypertension is esophagogastric varices bleeding, refractory ascites, and hepatic encephalopathy. The effective reduction of portal pressure can reduce the incidence of complications, improve the prognosis and reduce the mortality. At present, the commonly used clinical methods for reducing portal hypertension include drug therapy, minimally invasive interventions, surgical treatment, and liver transplantation. This article reviews the current status of integrated traditional Chinese and Western medicine for portal hypertension.
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OBJECTIVE To compare two administration methods of triamcinolone acetonide cream for the treatment of ear mycosis with pevison. METHODS Eighty-six cases diagnosed as the external auditory canal fungal infections with tympanic membrane perforation were randomly divided into observation group and control group, with 43 cases in each group. All the selected patients were positive in the external auditory meatal secretions fungus detection test, fungi and secretions of the external auditory canal are thoroughly cleaned under the endoscope. After ear canal cleaning, the obervation group was treated with Pevisone smeared on gelatin sponge which was evenly placed on the external auditory canal with fungal infection. The control group was treated with Pevisone smearing on external auditory canal by the patients themselves, twice a day. Two groups of patients come to the hospital every 3 days for review. After 2 weeks of treatment, the patients were followed up for 3 months, and the clinical efficacy of each group was compared. RESULTS The observation group was cured in 39 cases(90.7％), effective in 2 cases(4.7％), and ineffective in 2 cases(4.7％), The total efficiency rate is 95.3％.1 case recurred at 3 months of follow-up(2.4％). While in the control group, it was cured in 26 cases(60.5％), effective in 1 cases(2.3％), and ineffective in 16 cases(37.2％), the total efficiency rate is 62.8％.9 cases recurred at 3 months of follow-up(31.0％). The effect of the observation group was significantly higher than that of the control group(x2=14.508, P<0.05). CONCLUSION The ear endoscope can be used to remove the external auditory canal fungus thoroughly and has good visibility. Treating external auditory canal fungi disease with tympanic membrane perforation with gelatin sponge coated with triamcinolone acetonide cream has better clinical efficacy.
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OBJECTIVE To share surgical experience of ossicular chain malformations with CO2 laser.METHODS A retrospective analysis was performed.9 patients with clinical diagnosis of ossicular malformations underwent ossicular reconstruction with CO2 laser-assisted from May 2010 to Mar 2016,the results were evaluated by comparing preoperative and postoperative audiometric outcomes and the rate of postoperative complications.RESULTS 8 cases with complex lesion combining incus and stapes were found intraoperatively,the deformity located on stapes was showed in one case.The mean postoperative air conduction (AC) value was (26.53 ± 12.28) dB,the mean postoperative air-bone gap (ABG) was (9.44 ± 9.62) dB,the postoperative AC and ABG value improved considerably comparing with the preoperative value in all the patients,the difference was statistically significant.CONCLUTION CO2 laser is a suitable and effective adjunct in surgery for ossicular malformations such as otosclerosis.The use of the laser improves hearing results and operation efficiency and is not likely to increase side-effects to patients.
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Abundant experience has been accumulated when it comes to the traditional Chinese medicine (TCM) prevention and treatment of chronic hepatitis B (CHB). However, there still exist some deficiencies such as insufficient randomized controlled trials (RCTs) and lack of attention to objective indices for therapeutic evaluation. Therefore, future clinical prevention and treatment should be tied closely to the research progress in the immune pathogenesis of CHB and give full play to the characteristics and advantages of TCM in modulating the functional status (including immunity) of human body. Moreover, clinical and translational research on the TCM regulation of immune response in CHB should be carried out to further improve clinical therapeutic effect. In addition, biochemistry, virology, and pathology should be applied actively in place of outcomes while paying attention to the symptoms of patients in an effort to improve the objectivity of therapeutic evaluation when summarizing clinical practice experience. Furthermore, RCTs should be employed as much as possible to enhance global recognition of the therapeutic effect of TCM treatment. And there is no doubt that bringing the advantages of integrated traditional Chinese and Western medicine therapy into full play will benefit a huge number of patients.
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Abundant experience has been accumulated when it comes to the traditional Chinese medicine (TCM)prevention and treatment of chronic hepatitis B (CHB).However,there still exist some deficiencies such as insufficient randomized controlled trials (RCTs)and lack of attention to objective indices for therapeutic evaluation.Therefore,future clinical prevention and treatment should be tied closely to the re-search progress in the immune pathogenesis of CHB and give full play to the characteristics and advantages of TCM in modulating the func-tional status (including immunity)of human body.Moreover,clinical and translational research on the TCM regulation of immune response in CHB should be carried out to further improve clinical therapeutic effect.In addition,biochemistry,virology,and pathology should be ap-plied actively in place of outcomes while paying attention to the symptoms of patients in an effort to improve the objectivity of therapeutic e-valuation when summarizing clinical practice experience.Furthermore,RCTs should be employed as much as possible to enhance global rec-ognition of the therapeutic effect of TCM treatment.And there is no doubt that bringing the advantages of integrated traditional Chinese and Western medicine therapy into full play will benefit a huge number of patients.
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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.
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AIM:To investigate the regulatory effects of phosphatylinositol 3-kinase/protein kinase B (PI3K/PKB) signaling pathway on the expression of osteopontin ( OPN) in transforming growth factor-β1 ( TGF-β1 )-induced hu-man hepatic stellate cells .METHODS:Human hepatic stellate cell line LX-2 was cultured in DMEM and stimulated by TGF-β1 at the final concentration of 2.5, 5, 10 and 20 μg/L for 24 h or at final concentration of 10 μg/L for 12 h, 24 h and 48 h.LX-2 cells were pretreated with wortmannin , a specific inhibitor of PI3K/PKB signaling pathway , at final con-centration of 0.1 μmol/L for 1 h, followed by incubation with TGF-β1 at final concentration of 10μg/L for 24 h.The cells were collected.The expression of OPN was detected by real-time PCR and Western blotting .RESULTS: In LX-2 cells, the expression of OPN was apparently elevated when incubated with TGF-β1 .With the increase in TGF-β1 concentration or the extension of incubation hours , the expression of OPN was increased gradually in a dose-and time-dependent manner with certain limits.LX-2 cells pretreated with wortmannin and incubated with TGF-β1 had a significant decrease in the OPN expression as compared with control group (P<0.01).CONCLUSION:The expression of OPN in TGF-β1-induced LX-2 cells is regulated by the PI3K/PKB signaling pathway.
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<p><b>OBJECTIVE</b>To investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai, and to provide a scientific basis for developing prevention and treatment measures.</p><p><b>METHODS</b>From April 2005 to September 2014, 5,146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study. Clinical data of the 4,660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN. The incidence rate of cholestasis was assessed for relation to age, sex, etiology, and type of liver disease, and statistically compared to the general clinical data and specific biochemical indicators with potential sex-related differences. T-test and chi-square test were performed for the statistical analyses.</p><p><b>RESULTS</b>Of the 4,660 study participants, 10.26% had cholestasis; the prevalence of cholestasis increased with increasing age in male patients. The distribution of the cholestasis incidence according to the type of chronic liver disease was: 75.00%, primary sclerosing cholangitis; 42.86%, primary biliary cirrhosis; 35.97%, hepatic tumor; 30.77%, autoimmune hepatitis; 28.31%, drug-induced liver disease; 16.46%, alcoholic hepatitis; 13.98%, cryptogenic cirrhosis; 12.99%, schistosomal cirrhosis; 7.53%, alcoholic cirrhosis; 7.32%, mixed cirrhosis; 5.94%, viral liver cirrhosis; 2.70%, nonalcoholic fatty liver disease. There was no significant difference in the prevalence of cholestasis between the two sexes. In the patients with cholestasis, the levels of GGT and total bilirubin were significantly different between the two sexes.</p><p><b>CONCLUSION</b>The incidence rate of cholestasis in first-hospitalized patients with chronic liver disease was 10.26%, and the rate increased with increased age. Patients with primary sclerosing cholangitis or primary biliary cirrhosis had higher incidence rates of cholestasis. Incidence rates of cholestasis of the various chronic liver diseases were not related to sex.</p>
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Humans , Male , Bilirubin , China , Cholestasis , Chronic Disease , Incidence , Liver Diseases , Prevalence , Retrospective Studies , gamma-GlutamyltransferaseABSTRACT
<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>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Alleles , Asian People , Genetics , Case-Control Studies , Gene Frequency , Genetic Predisposition to Disease , Genotype , Hepatitis B, Chronic , Genetics , Polymorphism, Single Nucleotide , Suppressor of Cytokine Signaling Proteins , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To analyze the chemical compositions and their contents in non-alkaloids fraction from Radix Sophorae Tonkinensis.</p><p><b>METHOD</b>The non-alkaloids from Radix Sophorae Tonkinensis were analyzed by gas chromatography/mass spectrometry after trimethylsilyl derivatization. The chemical compositions were identified by comparison of the authentic sample and NIST database; the contents of 19 identified components were determined by linear regression equation.</p><p><b>RESULT</b>19 compounds constituting 34.72% of the non-alkaloids were identified. The major components were saccharides (5 compounds constituting 22.62%), organic acid (9 compounds constituting 11.81%), and others (5 compounds constituting 0.29%).</p><p><b>CONCLUSION</b>The GC-MS is a simple, rapid and sensitive method to investigate the complex primary metabolites in plants.</p>
Subject(s)
Gas Chromatography-Mass Spectrometry , Methods , Plant Roots , Chemistry , Sophora , ChemistryABSTRACT
Background: Chronic hepatitis C is one of the major causes of end-stage liver disease with a high incidence rate, amounting to a grave and serious problem of public health. Currently, interferon-based (with or without ribavirin) antiviral therapy has limited use due to its stringent indications, possible contraindications and side effects. Traditional Chinese medicine (TCM) may have advantages in the prevention and treatment of chronic hepatitis C and it is of significant value to discover the advantages. Through this research, a safe and effective treatment protocol of TCM or integrated TCM and Western medicine for chronic hepatitis C can be formed. To this end, during China's Eleventh Five-Year Plan, special research projects on acquired immune deficiency syndrome (AIDS), viral hepatitis and the other major infectious diseases were established. Our studies on chronic hepatitis C constitute one of the major special research topics. Methods and design: Clinical information of patients with chronic hepatitis C will be first collected in a large, multicenter epidemiological survey. Positive symptoms will be analyzed by rapid cluster analysis, principal constituent analysis and factor analysis, and syndrome types will be diagnosed based on expert advice. Concurrently, a large, multicenter, randomized, parallel-group prospective study will be launched based on evidence-based medical principles to evaluate the effects and safety of the treatment protocol for chronic hepatitis C. The evaluated indexes will include the normalization rate of liver function, virological improvement and quality of life improvement for the short-term efficacy and the incidence of liver cirrhosis and (or) primary liver cancer and mortality for the long-term efficacy. Discussion: This study will investigate the TCM syndrome differentiation norms and the syndrome distribution rules of chronic hepatitis C and evaluate the efficacy and safety of a treatment protocol for chronic hepatitis C based on TCM theory or combined treatment of TCM and Western medicine. The study results will be helpful to developing a TCM treatment program for chronic hepatitis C. Trial registration: The research program was registered in the Chinese Clinical Trial Registry in English and Chinese in January 2010. Registration number: ChiCTR-TRC-10000770.
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OBJECTIVE: A method based on dubious condition of information entropy was introduced and applied to discuss a complexity problem in the analysis of correlation between traditional Chinese medicine (TCM) syndrome and season. METHODS: Eight hundred and seventy one cases of chronic virus hepatitis B (hepatitis B) with TCM clinical data were analyzed by information entropy method. RESULTS: It was found that hepatitis B with Yin deficiency of liver and kidney happened more often in summer than in other seasons. CONCLUSION: It is inferred that the difference of seasons may influence the variation of TCM syndromes.
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AIM: To explore the treatment of subclinical hepatic encephalopathy(SHE) by traditional Chinese medicine. METHODS: Sixty patients with SHE were randomized into two groups: treatment group with 30 cases treated by Qingkai Granule and control group with another 30 cases treated by lactulose.They were all treated for two weeks.The evoked potentials(Eps) were measured,moreover,number connection test(NCT) and digit symbol test(DST) were conducted. RESULTS: In treatment group,the period for NCT was shorter and the DST also improved apparently;peak latency(PL) and interpeak latency(IPL) of SEP and AEPs were shorter to different degrees,with significant differences among groups. CONCLUSION: Qingkai Granule acts to effectively increase the learning,memory and space cognitive capacities in patients,and improves the nerve electrophysiology in patients.