Identification of circulating miRNA as early diagnostic molecular markers in malignant glioblastoma base on decision tree joint scoring algorithm.

PURPOSE: The lack of clinical markers prevents early diagnosis of glioblastoma (GBM). Many studies have found that circulating microRNAs (miRNAs) can be used as early diagnostic markers of malignant tumours. Therefore, the identification of novel circulating miRNA biomolecular markers could be beneficial to clinicians in the early diagnosis of GBM. METHODS: We developed a decision tree joint scoring algorithm (DTSA), systematically integrating significance analysis of microarray (SAM), Pearson hierarchical clustering, T test, Decision tree and Entropy weight score algorithm, to screen out circulating miRNA molecular markers with high sensitivity and accuracy for early diagnosis of GBM. RESULTS: DTSA was developed and applied for GBM datasets and three circulating miRNA molecular markers were identified, namely, hsa-miR-2278, hsa-miR-555 and hsa-miR-892b. We have found that hsa-miR-2278 and hsa-miR-892b regulate the GBM pathway through target genes, promoting the development of GBM and affecting the survival of patients. DTSA has better classification effect in all data sets than other classification algorithms, and identified miRNAs are better than existing markers of GBM. CONCLUSION: These results suggest that DTSA can effectively identify circulating miRNA, thus contributing to the early diagnosis and personalised treatment of GBM.

Integrated Tissue and Blood miRNA Expression Profiles Identify Novel Biomarkers for Accurate Non-Invasive Diagnosis of Breast Cancer: Preliminary Results and Future Clinical Implications.

We aimed to identify miRNAs that were closely related to breast cancer (BRCA). By integrating several methods including significance analysis of microarrays, fold change, Pearson's correlation analysis, t test, and receiver operating characteristic analysis, we developed a decision-tree-based scoring algorithm, called Optimized Scoring Mechanism for Primary Synergy MicroRNAs (O-PSM). Five synergy miRNAs (hsa-miR-139-5p, hsa-miR-331-3p, hsa-miR-342-5p, hsa-miR-486-5p, and hsa-miR-654-3p) were identified using O-PSM, which were used to distinguish normal samples from pathological ones, and showed good results in blood data and in multiple sets of tissue data. These five miRNAs showed accurate categorization efficiency in BRCA typing and staging and had better categorization efficiency than experimentally verified miRNAs. In the Protein-Protein Interaction (PPI) network, the target genes of hsa-miR-342-5p have the most regulatory relationships, which regulate carcinogenesis proliferation and metastasis by regulating Glycosaminoglycan biosynthesis and the Rap1 signaling pathway. Moreover, hsa-miR-342-5p showed potential clinical application in survival analysis. We also used O-PSM to generate an R package uploaded on github (SuFei-lab/OPSM accessed on 22 October 2021). We believe that miRNAs included in O-PSM could have clinical implications for diagnosis, prognostic stratification and treatment of BRCA, proposing potential significant biomarkers that could be utilized to design personalized treatment plans in BRCA patients in the future.

Prioritizing key synergistic circulating microRNAs for the early diagnosis of biliary tract cancer.

Biliary tract cancer (BTC) is a highly aggressive malignant tumor. Serum microRNAs (ser-miRNAs) serve as noninvasive biomarkers to identify high risk individuals, thereby facilitating the design of precision therapies. The study is to prioritize key synergistic ser-miRNAs for the diagnosis of early BTC. Sampling technology, significant analysis of microarrays, Pearson Correlation Coefficients, t-test, decision tree, and entropy weight were integrated to develop a global optimization algorithm of decision forest. The source code is available at https://github.com/SuFei-lab/GOADF.git. Four key synergistic ser-miRNAs were prioritized and the synergistic classification performance was better than the single miRNA' s. In the internal feature evaluation dataset, the area under the receiver operating characteristic curve (AUC) for each single miRNA was 0.8413 (hsa-let-7c-5p), 0.7143 (hsa-miR-16-5p), 0.8571 (hsa-miR-17-5p), and 0.9365 (hsa-miR-26a-5p), respectively, whereas the synergistic AUC value increased to 1.0000. In the internal test dataset, the single AUC was 0.6500, 0.5125, 0.6750, and 0.7500, whereas the synergistic AUC increased to 0.8375. In the independent test dataset, the single AUC was 0.7280, 0.8313, 0.8957, and 0.8303, and the synergistic AUC was 0.9110 for discriminating between BTC patients and healthy controls. The AUC for discriminating BTC from pancreatic cancer was 0.9000. Hsa-miR-26a-5p was a predictor of prognosis, patients with high expression had shorter survival than those with low expression. In conclusion, hsa-let-7c-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-26a-5p may act as key synergistic biomarkers and provide important molecular mechanisms that contribute to pathogenesis of BTC.

Serum soluble DR5 predicts mortality risk in patients with HBV-related hepatocellular carcinoma.

Introduction: Death receptor 5 (DR5) is significantly upregulated in various human tumor tissues; however, the relationship between serum levels of soluble DR5 (sDR5) and the mortality risk of hepatocellular carcinoma (HCC) is not understood. Our aim is to investigate the prognostic value of serum sDR5 in HCC patients. Methods: A total of 170 patients with HBV-HCC were recruited, with 82 and 88 patients as derivation and validation cohorts, respectively. sDR5 levels were analyzed using ELISA. The predictive factors for mortality were selected using LASSO regression analysis. Cox regression analysis was used to analyze the independent factors affecting mortality in 2 years. A nomogram based on the interquartile range of the sDR5 values predicted mortality rates. Results: Serum sDR5 level was identified as an independent risk factor for mortality in patients with HBV-HCC. The 2-year cumulative mortality rates of HBV-HCC were 10, 28.57, 38.10, and 95% across the sDR5 quartiles, respectively (p < 0.001). The sDR5 had an AUROC of 0.851 (95% CI: 0.755-0.920) in the derivation cohort. When the cut-off value was 30.06pg/mL, the AUROC of sDR5 was 0.778 (95% CI 0.677-0.860) in the validation cohort. The calibration curves fit well, and the decision curves showed that sDR5 had a high standardized net benefit. sDR5 predicted the prognosis of HBV-HCC patients most accurately. Further, serum sDR5 level was significantly positively associated with BCLC stage and the presence or absence of ascites. Conclusion: sDR5 showed high predictive accuracy in patients with HBV-HCC; thus, it is considered a new serological biomarker.

Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. PURPOSE: To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. METHODS: We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. RESULTS: After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1ß, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. CONCLUSION: YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.

Effectiveness and safety of electroacupuncture in treating Parkinson disease: A protocol for systematic review and meta-analyses.

BACKGROUND: Parkinson disease (PD) is an Extrapyramidal Disease mainly characterized by static tremor, myotonia, bradykinesia and postural gait disorder. As China's population ages, the number of people suffering from PD is increasing. Since there are many side effects of western medicine for Parkinson's patients, and the high price of the drugs make it difficult for many patients to adhere to treat. At present, many clinical studies have shown that electroacupuncture is effective in treating PD. Therefore, this systematic review aims to explore the effectiveness and safety of electroacupuncture in the treatment of PD. METHODS: Comprehensive search of PubMed, Embase, Medline, Cochrane Database of Systematic Reviews, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wang Fang Database from inception to February 2021, the literature selected is not restricted by language. In addition, we will search for unpublished studies and the references that were originally included in the literature manually. There were two reviewers screened the data and cross-checked the information individually, the quality of the literature was assessed by reviewers independently. The outcomes of interest include:the scale of Unifified PD Rating Scales, the Webster scale, the Quality of Life Questionnaire, total effective rate, recurrence rate, adverse events. The laboratory inspection indicators include:the content of lipid peroxidase, Superoxide dismutase activity in plasma and erythrocyte. The relevant randomized controlled trials will be included in this study. And we will evaluate the quality of the selected literature according to the Cochrane Handbook. Meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test will be implemented in the included literature, the tests' thresholds will be P < .1 and I2 > 50%. We will use either fixed effects model or random effects model according to the size of heterogeneity. RESULTS: The results of this systematic review will provide a comprehensive evidence for the clinical treatment of PD, and we will report this result soon. CONCLUSION: This paper will explore whether or not electroacupuncture can be used as a non-drug therapy for PD. ETHICS AND DISSEMINATION: Ethical approval is not required for this paper, our plan will be published in the journal. TRIAL REGISTRATION NUMBER: INPLASY202120031.

Chlorogenic Acid Decreases Malignant Characteristics of Hepatocellular Carcinoma Cells by Inhibiting DNMT1 Expression.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the adult liver, exhibiting rapid progression and poor prognosis. Chlorogenic acid (CGA), a polyphenol, has several biological activities, including the suppression of liver cancer cell invasion and metastasis. Increased levels or alterations in the function of DNMT1 are associated with the inactivation of tumor suppressor genes. However, the CGA-affected DNMT1 expression mediated mechanism is still unclear. METHODS: The human hepatocellular carcinoma (HCC) HepG2 cells were treated with a positive control drug (5-AZA) or varying doses of CGA. DNA methyltransferase 1 (DNMT1) protein levels and other relevant proteins were evaluated using Western blotting and immunocytochemistry. Cell-cycle analysis was performed by flow cytometry-based PI staining, and cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transwell invasion and wound healing assays were used to evaluate cell migration and invasion. In vivo proliferation of the HCC cells was detected. We investigated the expression of DNMT1, p53, p21, p-ERK, MMP-2, and MMP-9 in tumors using immunohistochemical analysis. RESULTS: Our results showed that CGA inhibited the proliferation, colony formation, invasion, and metastasis of HepG2 cells both in vitro and in vivo by down-regulating DNMT1 protein expression, which enhanced p53 and p21 activity, and resulting in a significant reduction in cell proliferation and metastasis. Moreover, CGA inactivated ERK1/2 and reduced MMP-2 and MMP-9 expression in HepG2 cells. CONCLUSIONS: CGA can suppress liver cancer cell proliferation, invasion, and metastasis through several pathways. CGA could serve as a candidate chemopreventive agent for HCC.

Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage.

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.

Lamivudine improves short-term outcome in hepatitis B virus-related acute-on-chronic liver failure patients with a high model for end-stage liver disease score.

AIM: Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) has significant morbidity and mortality. There is no standard approach for the management of HBV-related ACLF with nucleos(t)ide analogs. Our objective was to compare the short-term mortality between entecavir (ETV) and lamivudine (LAM) in patients with HBV-related ACLF. METHODS: We recruited 311 inpatients with HBV-related ACLF from December 2002 to January 2015. The patients were treated with ETV (n=143) or LAM (n=168). The primary endpoint was mortality rate at week 8. Virological and biochemical responses were also studied. RESULTS: By week 8, 53 (37.06%) patients in the ETV group and 57 (33.93%) patients in the LAM group died, and the two groups had similar mortality (P=0.414). Multivariate analysis showed that age, total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD) score were independent factors for mortality at week 8. The best cut-off value of the MELD score was 24.5 for 8-week mortality. Twenty-nine of the 170 (17.06%) patients with MELD score less than 24.5 died at week 8, and the ETV and LAM groups had similar mortality (P=0.743). Eighty-one of the 141 (57.45%) patients with MELD score of at least 24.5 died at week 8 and the LAM group had lower mortality than the ETV group (P=0.018 at week 4; P=0.039 at week 8). Both groups showed similar virological and biochemical responses at 4 weeks. CONCLUSION: LAM reduces the 8-week mortality rate significantly in patients with HBV-related ACLF who had MELD score of at least 24.5.

Noninvasive predictive models of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: The aim of the present study was to establish noninvasive diagnostic models for liver fibrosis and assess their predictive accuracy (AC). METHODS: A total of 349 patients with chronic hepatitis B virus infection were evaluated, who underwent liver biopsy and pathologic examination at Beijing Ditan Hospital affiliated to Capital Medical University. Patients were subdivided in disease-immune tolerant (n = 125) and immune reactive HBeAg positive (n = 224) groups. Diagnostic models were based on independent markers of liver fibrosis. Receiver operating characteristic (ROC) curves were used to set cutoff values and determine the diagnostic value of the models. RESULTS: Wang I and Wang II models were constructed using independent disease markers. Wang I model cutoff values ≤ 1.75 and > 5.84 were used to identify patients in the immune tolerant phase with or without significant fibrosis. The area under the ROC curve (AUC) for this model was 0.866 (95% CI, 0.790, 0.942) and an AC of 92.0% was obtained. Wang II model cutoff values ≤ 3.79 and > 7.06 were used to identify immune reactive HBeAg-positive patients with or without significant fibrosis. AUC was 0.872 (95% CI, 0.824, 0.920), with an AC of 88.0%. CONCLUSIONS: Both Wang models enabled noninvasive liver fibrosis assessment with reliable predictive power and reproducibility for diagnosis of fibrosis in immune tolerant and immune reactive HBeAg-positive patients. With further development, these models may provide a clinical alternative to liver biopsy.

Impact of obesity upon prostate cancer-associated mortality: A meta-analysis of 17 cohort studies.

A number of epidemiological studies have suggested that obesity is associated, albeit inconsistently, with the incidence of prostate cancer (PCa). In order to provide a quantitative assessment of this association, the present study examined the correlation between obesity and the incidence and associated mortalities of PCa in an updated meta-analysis of cohort studies. The cohort studies were identified by searching the EMBASE and MEDLINE databases on January 1, 2014. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. In total, 17 studies, which included 3,569,926 individuals overall, were selected according to predefined inclusion criteria. Based upon the results of the random-effects models, obesity was not significantly correlated with the incidence of PCa (RR, 1.00; 95% CI, 0.95-1.06). However, further analysis revealed that obesity was significantly correlated with an increased risk of aggressive PCa (RR, 1.14; 95% CI, 1.04-1.25). Furthermore, an increased risk of PCa-associated mortality was significantly associated with obesity (RR, 1.24; 95% CI, 1.15-2.33), without any heterogeneity between the studies (I2=0.0%; P=0.847). The present study provides preliminary evidence to demonstrate that obesity is a significant risk factor for aggressive PCa and PCa-specific mortality. The low survival rates observed among obese males with PCa may be a likely explanation for this association.

[Clinical analysis of 298 cases of liver cirrhosis and renal dysfunction].

OBJECTIVE: To evaluate the renal function of 298 liver cirrhosis cases among the patient population of Beijing Ditan Hospital. METHODS: The medical database of Beijing Ditan Hospital was retrospectively searched for patients with liver cirrhosis (compensated and decompensated). Patients were excluded from the study according to the presence of concomitant serious diseases, such as hypertension, diabetes, and malignancies.The consistency of renal insufficiency was evaluated by the glomerular filtration rate (eGFR) or serum creatinine (SCr) level, which were applied to the simplified modification of diet in renal disease (MDRD) equation.The renal function was compared between groups stratified according to compensated/decompensated status, sex, and age.The factors affecting renal insufficiency were screened.Measurement data were compared using the t-test and count data were compared using the chi-square test.Multiple sets of data were compared using analysis of variance.Correlations were assessed using multivariate logistic regression analysis, and the confounding variables were controlled with the Mantel-Haenszel method. RESULTS: A total of 298 hospitalized patients with liver cirrhosis were included in the study, among which 41 had compensated cirrhosis and 257 had decompensated cirrhosis.Twenty patients (6.7%) with renal insufficiency were identified by SCr measurement and 62 patients (20.8%) were identified by eGFR, and the number identified was significantly different between the two groups (x2=42.00, P less than 0.05).Fifty-six (21.8%) patients had decompensated cirrhosis and 6 (14.6%) patients had decompensated cirrhosis with renal dysfunction; the eGFR levels for these two groups were (117.75 +/- 32.60) ml/min/(1.73 m2)-1 and (112.72 +/- 24.01) ml/min/(1.73 m2) respectively and the difference was not statistically significant (P more than 0.05).The incidence of renal dysfunction among female patients was 22.7% (17/75), and the incidence among male patients was 20.2% (45/223); the eGFR levels for these two groups were (110.07 +/- 26.60) ml/min/(1.73 m2)1 and (112.49 +/- 33.05) ml/min/(l.73 m2) respectively, and the difference was not statistically significant (P more than 0.05).The rate of renal dysfunction among patients aged 20 to 40 years-old, more than 40 to 60 years-old, and more than 60 years years-old was 5.7% (4/70), 22.5% (40/178), and 36.0%(18/50) respectively; the eGFR values for these two groups were (123.43 +/- 24.42) ml min/(l.73 m2), (111.18+/- 33.57) ml/min/(1.73 m2), and (98.20 +/- 27.04) ml/min/(1.73 m2), and the differences were not statistically significant (P less than 0.05).After stratification of the study population by age, the patient sex and the cirrhosis stage were not significantly different (P more than 0.05).Multivariate logistic regression analysis identified age as a risk factor of hepatitis B-related cirrhosis and renal dysfunction (P less than 0.05). CONCLUSION: The simplified MDRD equation can help clinicians determine whether patients have kidney injury.Development of renal dysfunction in patients with liver cirrhosis is not associated with patient sex and cirrhosis stage, but is precisely correlated with patient age.

Association of TNF-α, TNFRSF1A and TNFRSF1B gene polymorphisms with the risk of sporadic breast cancer in northeast Chinese Han women.

BACKGROUND: The interaction of tumor necrosis factor-α (TNF-α) with its receptors: TNFRSF1A and TNFRSF1B is critical for the promotion of tumor growth, invasion and metastasis. To better understand the roles of single nucleotide polymorphisms (SNPs) in the TNF-α, TNFRSF1A and TNFRSF1B genes in the development of breast cancer, we explored the associations between SNPs in these three genes and breast cancer susceptibility in northeast Chinese Han women. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study was conducted among 1016 breast cancer patients and 806 age-matched healthy controls. Seven SNPs in the TNF-α (rs1800629, rs361525), TNFRSF1A (rs767455, rs4149577 and rs1800693) and TNFRSF1B (rs1061622 and rs1061624) genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In TNFRSF1B, the rs1061622 GT genotype and the G allele conferred a reduced susceptibility to breast cancer (P = 0.000662, OR = 0.706, 95% CI: 0.578-0.863; P = 0.002, OR = 0.769, 95% CI; 0.654-0.905, respectively). Moreover, the AG genotype, the AA genotype and the A allele in rs1061624 conferred an increased risk of breast cancer (P = 0.007, OR = 1.470, 95% CI:1.112-1.943; P = 0.00109, OR = 1.405 95% CI:1.145-1.724; P = 0.001, OR = 1.248 95% CI:1.092-1.426, respectively). These two SNPs also had associations with breast cancer risk under the dominant model. In haplotype analysis, the CTA (rs767455 C-rs4149577 T-rs1800693 A) haplotype in TNFRSF1A and the TA (rs1061622 T-rs1061624 A) haplotype in TNFRSF1B had higher frequencies in breast cancer patients (P = 0.00324; P = 0.000370, respectively), but the frequency of GG (rs1061622 G-rs1061624 G) haplotype in TNFRSF1B was lower in breast cancer patients (P = 0.000251). The associations of the three haplotypes remained significant after correcting for multiple testing. In addition, significant associations were also observed between TNFRSF1A polymorphisms and lymph node metastasis, P53, estrogen receptor (ER) and progesterone receptor (PR) statuses. CONCLUSIONS: Our results suggest that rs1061622 and rs1061624 in TNFRSF1B may affect breast cancer risk, and SNPs in TNFRSF1A are associated with the clinical features of breast cancer.

[Efficacy and safety of integrative medical program based on blood cooling and detoxification recipe in treating patients with hepatitis B virus related acute-on-chronic liver failure: a randomized controlled clinical study].

OBJECTIVE: To evaluate the clinical efficacy and safety of integrative medical program based on blood cooling and detoxification recipe (BCDR) in treating patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) of heat-toxicity accumulation syndrome (HTAS). METHODS: Adopting randomized controlled clinical design, a total of 105 HBV-ACLF patients of HTAS were randomly assigned to the trial group (64 cases) and the control group (41 cases). Patients in the control group were treated with comprehensive Western therapy, while those in the trial group were treated with comprehensive Western therapy plus BCDR. All were treated for 8 weeks and followed up for 40 weeks. Effect and safety of the treatment were assessed, including fatality, liver functions [total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and aspartate transaminase (AST)], and prothrombin activity (PTA) after treatment and at week 48 of follow-ups. RESULTS: After 8-week treatment, there was statistical difference in the overall fatality rate (15.63% vs 34.15%), the fatality rate in the mid-term (25.0% vs 64.7%), TBIL at week 8 (64.54 +/- 79.75), AST [at week 2: (178.97 +/- 44.24) U/L vs (288.48 +/- 58.49) U/L; at week 4: (61.65 +/- 27.36) U/L vs (171.12 +/- 89.11) U/L] and PTA [at week 4: (58.30 +/- 15.29) vs (42.56 +/- 15.27); at week 6: (60.77 +/- 20.40) vs (43.08 +/- 12.79)] (all P < 0.05). At week 48 of the followup, the fatality rate of the trial group (21.88%) decreased by 17. 14% when compared with that of the control group (39.02%; P < 0.05). No obvious adverse event occurred in the two groups during the 8-week treatment period. CONCLUSION: BCDR could significantly reduce the mortality of HBV-ACLF patients.

[Randomized controlled study of integrated treatment of traditional Chinese medicine and western medicine on AIDS with pulmonary inflammation patients].

OBJECTIVE: To compare effects of integrated treatment traditional Chinese medicine and Western medicine (TCM-WM) and simple western medicine on TCM clincal symptoms in the patient of AIDS with pulmonary inflammation. METHOD: A multicenter randomized controlled trials of 164 subjects evaluated the effects of clinical symptoms of AIDS with pulmonary inflammation of TWO regimens: the TCM-WM group (n = 111) and western medicine treatment group (n = 53), while incidence of TCM symptoms in different time points in two groups were analyzed. RESULT: Twenty eight days after treatment, the cured and markedly effective rate of TCM symptoms in the TCM-WM group significantly exceeding that in the western medicine treatment group (cured and markedly effective rate significant efficiency 44.55% vs 20.00%), while the incidence rate for the TCM symptoms of fever and headache in the TCM-WM group was significantly lower than that in western medicine group. CONCLUSION: The integrated treatment of traditional Chinese medicine and Western medicine helps to alleviate the TCM clinical symptoms of AIDS with pulmonary inflammation.

WITHDRAWN: Noninvasive predictive models of liver fibrosis in patients with chronic hepatitis B.

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[Preliminary study on features of syndrome distribution and cluster analysis for AIDS patients with pulmonary infection].

OBJECTIVE: To investigate Chinese medical features of acquired immunodeficiency syndrome (AIDS) patients with pulmonary infection. METHODS: Using cluster analysis method, Chinese medical syndromes of 196 AIDS patients with pulmonary infection were analyzed. The distribution features of each syndrome type were analyzed according to the severity and CD4+ numerical analysis. RESULTS: Basic Chinese medical syndrome types could be summed up as three kinds: exterior invasion of wind heat and phlegm heat obstructing Fei syndrome (61 cases, 31.1%), Fei-Pi deficiency and Fei stagnation of phlegm syndrome (64 cases, 32.7%), Fei-Shen deficiency and yin deficiency induced inner heat syndrome (71 cases, 36.2%). There was statistical difference in the severity degree and the distribution of CD4 among the three syndrome types (P < 0.05). CONCLUSIONS: AIDS patients with pulmonary infection involve Fei, Shen, and Pi. The pathogenic factors were related to "wind", "heat", "phlegm", and "xu". The Chinese medical syndrome distribution was closely correlated with patients' immunity.

[Effect of Ganoderma lucidum polysaccharides on intestinal mucosal immune system in H22 liver cancer bearing mice].

OBJECTIVE: To observe the mucosal immune mechanism of anti-tumor action of Ganoderma lucidum polysaccharides (GLP). METHODS: The concentration of H22 cells in suspension were adjusted to 1 x 10(9)/ L, and 0.2 mL of the cell suspension was injected subcutaneously in the right oxter of Kunming mice. Then the H22 bearing mice were randomly divided into 4 groups: the GLP group, the Cytoxan (CTX) group, the CTX + GLP group and the untreated model group, 8 mice in each group. Besides, a blank control group was set up. Starting from the 2nd day of modeling, GLP, at the dose of 1.02 g/kg was given to GLP group and GLP + CTX group by gastrogavage once a day for 12 successive days; CTX at the dose of 100 mg/kg was administered via peritoneal injection to the CTX group and the GLP + CTX group on the 1st day and the 6th day of the experimental course; but to the model group and the blank group, only equal volume of distilled water was given. All mice were sacrificed on the 14th day, the ileum at 1 cm upper to cecum was taken, through 4% paraform fixation and paraffin section, it was used for immunohistochemical detecting expressions of immunoglobulin A (IgA), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-10 (IL-10) in ileum. Besides, the lymphocyte subsets in the intraepithelial lymphocyte (IEL), lamina propria lymphocytes (LPL), and Peyer's patch lymphocytes (PPL) were analyzed by immune fluorescence technique and flow cytometry. RESULTS: Compared with the blank control group, the phenotype of lymphocytes and the expression of cytokines in ileum in the model group changed significantly; and the phenotype was variant in different regions. Compared with the model group, both indexes were adjusted in the GLP, CTX and GLP + CTX group to different degrees. CONCLUSION: The adjustment of GLP on intestinal mucosal immune is probably another path for its anti-tumor action.

[Exploration on relationship between TCM syndrome type and expression of human leucocyte antigen locus-DRB1 in patients with chronic hepatitis B].

OBJECTIVE: To study the relationship between TCM syndrome type and expression of human leucocyte antigen-DRB1 (HLA-DRB1) in patients with chronic hepatitis B. METHODS: Using PCR method to amplify the related segments of DNA extracted from peripheral leucocytes by the routine methods, and gene array analysis was performed to detect the expression of HLA-DRB1. RESULTS: HLA-DRB1 * 13 was expressed in healthy person in the control group, but was not expressed in chronic hepatitis B patients, showing significant difference between the two groups. In the patients with five different syndrome types, i.e. the dampness blocking middle-jiao type (A), the Gan-stagnancy with Pi-deficiency type (B), the blood stasis blocking collaterals type (C), the Gan-Shen yin-deficiency type (D) and the Pi-Shen yang-deficiency type (E), the former three belonged to the excessive syndrome and the latter two were deficient syndrome. Most of the CHB patients were differentiated as excessive syndrome. CONCLUSION: Difference of HLA-DR expression exists between chronic hepatitis B patients and healthy persons, the action of the difference is remained for further confirmation. HLA-DR expression in patients with different syndrome types, excessive or deficient, might be different, too.

[An analysis of the relationship between HBV DNA and HBeAg expression and mortality in 799 severe hepatitis patients].

OBJECTIVE: To evaluate the relationship between mortality and HBVDNA and HBeAg expression of severe hepatitis B patients. METHODS: The mortality rates of different types of severe hepatitis patients in our hospital during the last five years were analysed. HBV DNA was detected using the fluorescence quantitative PCR method and the HBeAg expression of severe hepatitis B was studied using a microparticle method. RESULTS: (1) Hepatitis B morbidity was 83.5% in each type of severe hepatitis, and severe chronic hepatitis B morbidity was 96.77% in each type of severe chronic hepatitis. (2) The mortality rate of those with HBV DNA more than 1 x 10(5) copies/ml was 53.25% and the mortality of those with HBV DNA less than 1 x 10(5) copies/ml was 34.50% (P less than 0.01). The HBeAg expression had no influence on the death rate. (3) The death rate descended to 30.38% from 54.64% (HBV DNA more than 1 x 10(5) copies/ml) when treated with Lamivudine (P less than 0.01). CONCLUSION: In severe hepatitis the quantity of virus carried in the patient is one of the key factors of mortality; antivirus treatment can lower mortality.