Cost-effectiveness analysis of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma.

BACKGROUND: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system. METHODS: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results. RESULTS: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage. CONCLUSION: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.

Proteomic investigation and biomarker identification of lung and spleen deficiency syndrome in HIV/AIDS immunological nonresponders.

Background: Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) immunological nonresponders (HIV/AIDS-INRs) whose CD4+ cell counts do not rebound after highly active antiretroviral therapy (HAART) treatment usually experience severely impaired immune function and high mortality. Traditional Chinese medicine (TCM) has many advantages in the field of AIDS, especially its promotion of patients' immune reconstitution. Accurate differentiation of TCM syndromes is a prerequisite for guiding an effective TCM prescription. However, the objective and biological evidence for identification of the TCM syndromes in HIV/AIDS-INRs remains lacking. Lung and spleen deficiency (LSD) syndrome, a typical HIV/AIDS-INR syndrome, was examined on in this study. Methods: We first performed a proteomic study of LSD syndrome in INRs (INRs-LSD) using tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS) and screened them against the healthy and undocumented identifiable groups. The TCM syndrome-specific proteins were subsequently validated based on bioinformatics analysis and enzyme-linked immunosorbent assay (ELISA). Results: A total of 22 differentially expressed proteins (DEPs) were screened in INRs-LSD compared to the healthy group. Based on bioinformatic analysis, these DEPs were found to be mainly associated with the immunoglobin A (IgA)-generated intestinal immune network. In addition, we examined the TCM syndrome-specific proteins alpha-2-macroglobulin (A2M) and human selectin L (SELL) with ELISA and found that they were both upregulated, which was consistent with the proteomic screening results. Conclusions: A2M and SELL were finally identified as potential biomarkers for INRs-LSD, providing a scientific and biological basis for identifying typical TCM syndromes in HIV/AIDS-INRs and an opportunity to build a more effective TCM treatment system for HIV/AIDS-INRs.

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.

Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation.

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid-activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate-induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.

Comparative serum microRNA array analysis of the spleen-stomach dampness-heat syndrome in different diseases: Chronic hepatitis B and chronic gastritis.

Spleen-stomach dampness-heat syndrome (SSDHS) is the common Traditional Chinese Medicine (TCM) syndrome observed in both chronic hepatitis B (CHB) and chronic gastritis (CG). The specialized TCM prescription for CHB and CG patients with SSDHS is same, but there is limited information about the biological characteristics of this TCM syndrome. This study aimed to identify the serum miRNAs profile for the SSDHS in two different diseases in order to evaluate the miRNA-mediated biological characteristics of this TCM syndrome. We performed comparative microarray analysis of serum miRNA expression profiles in 10 CHB patients with SSDHS (SSDHS-CHB), 10 CG patients with SSDHS (SSDHS-CG), and 10 healthy controls (HC). The selected miRNAs were further validated by qRT-PCR in 13 SSDHS-CHB patients, 13 SSDHS-CG patients, and 13 HC. Moreover, bioinformatics analysis (GO and KEGG pathway enrichment analyses) was applied to identify the involved target genes and pathways for these selected miRNAs. Nine significantly differentially expressed (SDE)-miRNAs in the SSDHS-CHB group and 24 SDE-miRNAs in the SSDHS-CG group were identified, compared with the HC group (fold change >2.0 and p < .05). Among these, upregulated hsa-miR-483-3p and downregulated hsa-miR-223-3p were identified as the common SDE-miRNAs for both SSDHS-CHB and SSDHS-CG groups. Bioinformatics analysis of the common SDE-miRNA's target genes showed their involvement in the regulation of inflammation, immune response, and tumorigenesis. SSDHS-specific hsa-miR-483-3p and hsa-miR-223-3p identified in this study indicated a relevance to the underlying biological basis of SSDHS, and may provide scientific basis for the application of same TCM prescription in CHB and CG.

Study on the Expression Differences and the Correlation with H2BE Gene of Th Related Cytokines in SSDHS and LDSDS TCM-Syndromes of CHB Patients.

Although our previous studies revealed that H2BE exhibited significantly differential expression between two CHB TCM-syndromes: Spleen-stomach dampness-heat syndrome, SSDHS and liver-depression spleen-deficiency syndrome, LDSDS, the underlying mechanisms remain largely unknown. Recent studies showed that dynamic expression fluctuation of Th related cytokines in CHB TCM-syndromes, and furthermore, their expression levels were largely regulated by H2BE. This study aims to detect the expression level differences of Th related cytokines between these two TCM-syndromes and further investigate the underlying regulatory mechanisms. The expression levels of the four Th related cytokines and H2BE were analyzed and the protein-protein interaction networks between H2BE and the four cytokines were constructed. Our results suggested that almost all the cytokines were significantly upregulated compared with the healthy group (P < 0.05). Interestingly, among the four cytokines, only IL-4 and INF-γ showed statistical significance between these two syndromes. The protein-protein interaction networks demonstrated that H2BE was indirectly associated with IL-4 and IL-10, and H2BE may regulate the expression levels of cytokines through GATA3. Taken together, our results indicated that IL-4 and INF-γ are two representative cytokines that may serve as two potential biochemical indicators of SSDHS and LDSDS in CHB patients; except what has been reported, our study found that one possible way for H2BE to regulate the expression of cytokines is to interact with GATA3 directly or indirectly.

Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study.

BACKGROUND: Hyperandrogenism (HA), inflammation, and oxidative damage play key roles in the pathophysiology of polycystic ovary syndrome (PCOS). Whether vitamin D adjuvant therapy improves hormonal, inflammation, and oxidative damage in PCOS patients has aroused widespread interest, but the results are controversial. To evaluate the effect of vitamin D supplementation on hormonal, oxidative stress, and inflammatory parameters in patients with PCOS. METHODS: A literature search was conducted in Medline, the Cochrane Library, EMBASE, and Web of Science for studies related to PCOS and vitamin D supplementation. All reports of randomized controlled trials (RCTs) published before December 2019 were identified. The fixed-effects model or random-effects model was used to calculate pooled estimates of standardized differences in means (SMD) with 95% confidence intervals (CI). RESULTS: A total of 956 identified studies were retrieved, and eighteen RCTs involving 1,060 participants were ultimately included in the current meta-analysis. The pooled results demonstrated that vitamin D supplementation in patients with PCOS resulted in a significant improvement in serum total testosterone (TT), high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and malondialdehyde (MDA). No significant effect on free testosterone (FT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), free androgen index (FAI), nitric oxide (NO), and total glutathione (GSH) levels was found. Subgroup analysis showed that vitamin D supplementation reduced hs-CRP and MDA irrespective of the treatment course, type of vitamin D intervention, supplementation frequency, and dosage. Twelve weeks of vitamin D supplementation improved TT and TAC while low-dose vitamin D supplementation (≤1,000 IU/day) improved TT and DHEA-S. Vitamin D co-supplementation reduced TT, FT, and DHEA-S, while a daily supplementation regime improved TT, DHEA-S, and TAC in patients with PCOS. CONCLUSIONS: The current meta-analysis demonstrates that vitamin D supplementation in patients with PCOS resulted in an improvement in the levels of TT, hs-CRP, TAC, and MDA, but did not affect FT, DHEA-S, SHBG, FAI, NO, and GSH levels. Vitamin D co-supplementation, low-dose vitamin D supplementation (≤1,000 IU/day), and daily supplementation frequency appeared to be more conducive to improving hormones, inflammation, and oxidative stress in PCOS patients.

Biological differentiation of traditional Chinese medicine from excessive to deficient syndromes in AIDS: Comparative microRNA microarray profiling and syndrome-specific biomarker identification.

Traditional Chinese medicine (TCM) has been widely applied as a supplementary therapy of human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) in China. TCM has a positive effect on improving the quality of life, prolonging life, and ameliorating the symptoms of HIV/AIDS patients. Yang deficiency of spleen and kidney (YDSK) syndrome is a typical deficient TCM syndrome in AIDS patients, and accumulation of heat-toxicity (AHT) syndrome is a common excessive syndrome in the earlier stage of AIDS. Thus, accurate diagnosis of these two syndromes can improve the targeted treatment effect, and predict the prognosis of the disease. However, the scientific basis of TCM syndromes remains lacking, greatly hindering the accuracy of diagnosis and effectiveness of treatment. In this research, microRNA (miRNA) microarray and quantitative real-time polymerase chain reaction combined with bioinformatics were used for comparative analysis between YDSK and AHT patients. Significantly differential expressed miRNAs (SDE-miRNAs) of each TCM syndrome were identified, including hsa-miR-766-3p and hsa-miR-1260a and so on, as well hsa-miR-6124, hsa-let-7g-5p and so on, for YDSK and AHT, respectively. Biological differences were found between their SDE-miRNAs based on bioinformatics analyses, for example, ErbB signaling pathway mainly linked to AHT, while focal adhesion dominated in YDSK. Syndrome-specific SDE-miRNAs were further identified as potential biomarkers, including hsa-miR-30e-5p, hsa-miR-144-5p for YDSK and hsa-let-7g-5p, hsa-miR-126-3p for AHT, respectively. All of them have laid biological and clinical bases for TCM diagnosis and treatment of AIDS syndrome at the miRNA level, offering potential diagnostic indicators of immune reconstitution.

Clinical efficacy and safety of Ganshuang granules as an adjuvant treatment for chronic hepatitis B liver fibrosis: A protocol for systematic review and meta analysis.

BACKGROUND: Chronic hepatitis B liver fibrosis is significant public concern. Ganshuang granules (GSG) are used to treat liver fibrosis for a long time. The aim of this study is to synthesize related data to explore efficacy and safety of GSG as an adjuvant treatment for chronic hepatitis B liver fibrosis. METHODS: Electronic database were used to identify related studies. We chose PubMed, China Knowledge Network Infrastructure, China Biomedical Database, Wan Fang Data, VIP Database, EMBASE, and Cochrane Library as retrieval tool. Two independent individuals conducted the publication selection, data extraction, data assessment. Any problems between 2 researchers will be resolved by a third reviewer through negotiation. RevMan 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) software will be used for data analysis. RESULTS: This study will systematically detect the efficacy and safety of GSG for treating chronic hepatitis B liver fibrosis. CONCLUSION: This study will provide scientific evidence to explorer whether GSG are efficacy and safety in treating chronic hepatitis B liver fibrosis. PROSPERO REGISTRATION NUMBER: INPLASY202090027.

Biological Differentiation of Dampness-Heat Syndromes in Chronic Hepatitis B: From Comparative MicroRNA Microarray Profiling to Biomarker Identification.

Increasing interest is aroused by traditional Chinese medicine (TCM) treatment of chronic hepatitis B (CHB) based on specific TCM syndrome. As the most common CHB syndromes, spleen-stomach dampness-heat (SSDH) syndrome and liver-gallbladder dampness-heat (LGDH) syndrome are still apt to be confused in TCM diagnosis, greatly hindering the stable exertion of TCM effectiveness. It is urgently needed to provide objective and biological evidences for differentiation and identification of the two significant syndromes. In this study, microRNA (miRNA) microarray analyses coupled with bioinformatics were employed for comparative miRNA profiling of SSDH and LGDH patients. It was found that the two syndromes had both the same and different significantly differentially expressed miRNAs (SDE-miRNAs). Commonness and specificity were also both found between their SDE-miRNA-based bioinformatics analyses, including Hierarchical Clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and miRNA-GO/pathway networks. Furthermore, syndrome-specific SDE-miRNAs were identified as the potential biomarkers, including hsa-miR-1273g-3p and hsa-miR-4419b for SSDH as well as hsa-miR-129-1-3p and hsa-miR-129-2-3p for LGDH. All these laid biological and clinical bases for classification and diagnosis of the two significant CHB dampness-heat syndromes including SSDH and LGDH, providing more opportunities for better application of TCM efficacy and superiority in CHB treatment.

HLA-DQB1/DRB1 Alleles Associate with Traditional Chinese Medicine Syndrome of Chronic Hepatitis B: A Potential Predictor of Progression.

BACKGROUND AND AIMS: Traditional Chinese medicine (TCM) has been widely applied in chronic hepatitis B (CHB) supplementary treatment in China. Kidney yang deficiency syndrome (KYDS), one of the most common TCM syndromes of CHB, is more likely to progress to liver cirrhosis or hepatocellular carcinoma than other syndromes. Polymorphisms in the human leucocyte antigen- (HLA-) DQB1 and -DRB1 genes were reported to be associated with hepatitis B virus infection outcomes. Here, we investigated whether HLA-DQB1 and HLA-DRB1 are associated with the classification of CHB TCM syndromes. METHODS: We genotyped HLA-DQB1 and HLA-DRB1 alleles in a total of 105 subjects, including 74 CHB patients (28 KYDS and 46 non-KYDS) and 31 healthy individuals from Sichuan Province of Southwest China, by polymerase chain reaction sequence-based typing (PCR-SBT). Moreover, a meta-analysis was carried out for further verification. RESULTS: The proportion of patients with high HBV DNA load (≥2000 IU/ml) in the KYDS group is higher than that in the non-KYDS group (60.70% [17/28] vs. 28.30% [13/46]); P=0.01). The frequencies of HLA-DQB1∗02:01 (P=0.04) and HLA-DRB1∗03:01 (P=0.04) in the KYDS group were significantly increased compared to the non-KYDS group. The gene test and meta-analysis showed that HLA-DRB1∗08:03 confers susceptibility to CHB (odds ratio = 1.57). CONCLUSION: We found an association between HLA-DRB1/DQB1 polymorphisms and KYDS of CHB. Moreover, KYDS patients of CHB are characteristic with high HBV DNA loads. These findings help to reveal the biological mechanism of KYDS in high risk of CHB progression and suggest a potential prognostic value for disease outcome evaluation.

Preventive effect on endothelial surface layer damage of Fusu agent in LPS-induced acute lung injury in rats.

Acute lung injury (ALI) is one of major causes of morbidity and mortality in intensive care. In pathophysiological events of ALI, endothelial surface layer (ESL) injury can result in capillary leakage as the initial event. The "Fusu agent", a traditional Chinese medicine, can inhibit inflammatory factors, attenuate lung capillary leak as seen in our previous study. This study was aimed to explore the molecular mechanism of Fusu agent treatment with ALI. Consistent with previous studies, we found that Fusu agent has the protective effect on LPS-induced ALI model rats. Further investigation demonstrated that heparanase activation is necessary for the LPS-induced ALI model to aggravate ESL loss. Fusu agent can inhibit heparanase activation and heparan sulfate proteoglycans' (HSPGs) degradation to mitigate the ESL injury. Furthermore, TNF-α and intercellular adhesion molecule-1 (ICAM-1) were significantly reduced upon Fusu agent pre-treatment to inhibit inflammatory cell influx and neutrophil adhesion in ALI. These findings shed light on the pharmacologic basis for the clinical application of traditional Chinese medicine in treating ALI.

The therapeutic effects of traditional Chinese medicine Fusu agent in LPS-induced acute lung injury model rats.

PURPOSE: Acute lung injury (ALI) is a common and fatal oxidative stress in the lung, mainly induced by endothelial injury and capillary leakage. In our previous study, "Fusu agent", a traditional Chinese medicine, was found to exert preventive effect on endothelial damage in lipopoly-saccharide (LPS)-induced ALI model rats partially via inhibiting heparanase1 (HPA1) activation and inhibiting the inflammatory factors. However, it is still unknown whether Fusu agent exerts its therapeutic effect in LPS-induced ALI model rats and its potential mechanism. MATERIALS AND METHODS: Rats were injected with LPS (3 mg/kg, intraperitoneally) to induced ALI, and the prepared Fusu agent was given (2, 4 or 6 g/kg) 2 hours after LPS challenge. Twenty-four or 48 hours after Fusu agent administration, the biochemical changes in the plasma and lung tissues and the morphological/histological changes in the lung associated with inflammation and injury were evaluated. Human umbilical vein endothelial cells (HUVECs) were employed to confirm the therapeutic effects of Fusu agent and investigate its mechanisms, that is, affecting ROS accumulation, mitochondrial transmembrane potential (MTP) maintenance and decreasing the expression levels of HPA1. RESULTS: Administration of Fusu agent obviously improved the lung injury and recovered vascular endothelium loss and injury. CD31 signal, which is a specific marker for endothelial vascular lesions, was decreased after Fusu agent treatment in LPS-induced ALI model rats, indicating its therapeutic effect against endothelial surface layer injury. Meanwhile, Fusu agent also decreased HPA1 expression and inflammatory responses. In vitro, Fusu agent-medicated serum decreased injury and cell death induced by LPS in HUVECs by stabilizing MTP and decreasing the leakage of lactate dehydrogenase. Consistently, Fusu agent-medicated serum downregulated HPA1 induced by LPS stimulation. CONCLUSION: These findings suggest that Fusu agent exerts its therapeutic effect in both LPS-induced ALI model rats and HUVECs potentially via suppressing HPA1 expression, and thus exerts prosurvival effect via maintaining MTP and attenuating cell injury.

Comparative Proteomic Profiling and Biomarker Identification of Traditional Chinese Medicine-Based HIV/AIDS Syndromes.

Given the challenges in exploring lifelong therapy with little side effect for human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) cases, there is increasing interest in developing traditional Chinese medicine (TCM) treatments based on specific TCM syndrome. However, there are few objective and biological evidences for classification and diagnosis of HIV/AIDS TCM syndromes to date. In this study, iTRAQ-2DLC-MS/MS coupled with bioinformatics were firstly employed for comparative proteomic profiling of top popular TCM syndromes of HIV/AIDS: accumulation of heat-toxicity (AHT) and Yang deficiency of spleen and kidney (YDSK). It was found that for the two TCM syndromes, the identified differential expressed proteins (DEPs) as well as their biological function distributions and participation in signaling pathways were significantly different, providing biological evidence for the classification of HIV/AIDS TCM syndromes. Furthermore, the TCM syndrome-specific DEPs were confirmed as biomarkers based on western blot analyses, including FN1, GPX3, KRT10 for AHT and RBP4, ApoE, KNG1 for YDSK. These biomarkers also biologically linked with the specific TCM syndrome closely. Thus the clinical and biological basis for differentiation and diagnosis of HIV/AIDs TCM syndromes were provided for the first time, providing more opportunities for stable exertion and better application of TCM efficacy and superiority in HIV/AIDS treatment.

iTRAQ-Based Proteomics Identification of Serum Biomarkers of Two Chronic Hepatitis B Subtypes Diagnosed by Traditional Chinese Medicine.

Background. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM) pattern classification, damp heat stasis in the middle-jiao (DHSM) and liver Qi stagnation and spleen deficiency (LSSD) are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively. LSSD-CHB and DHSM-CHB shared 142 upregulated and 84 downregulated proteins, of which several proteins have been reported to be candidate biomarkers, including immunoglobulin (Ig) related proteins, complement components, apolipoproteins, heat shock proteins, insulin-like growth factor binding protein, and alpha-2-macroglobulin. In addition, we identified that proteins might be potential biomarkers to distinguish LSSD-CHB from DHSM-CHB, such as A0A0A0MS51_HUMAN (gelsolin), PON3_HUMAN, Q96K68_HUMAN, and TRPM8_HUMAN that were differentially expressed exclusively in LSSD-CHB patients and A0A087WT59_HUMAN (transthyretin), ITIH1_HUMAN, TSP1_HUMAN, CO5_HUMAN, and ALBU_HUMAN that were differentially expressed specifically in DHSM-CHB patients. Conclusion. This is the first time to report serum proteins in CHB subtype patients. Our findings provide potential biomarkers can be used for LSSD-CHB and DHSM-CHB.

Antioxidant and antibacterial activity of two compounds (forsythiaside and forsythin) isolated from Forsythia suspensa.

Forsythia suspensa (Thunb.) Vahl. has been widely used in traditional medicines in Asia to treat gonorrhoea, erysipelas, inflammation, pyrexia, ulcer and other diseases. Recently the investigation has been focused on the antioxidant and antibacterial activity of this plant. However, limited scientifically proven information is available. We isolated two compounds (forsythiaside and forsythin) from this plant. The aims of this investigation, therefore, were to assay antioxidant activity and antibacterial properties of the two main and distinctive compounds isolated and to exploit antioxidants and antibacterial agents from natural compounds. The antioxidant activity was estimated using the 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity method and the in-vitro antimicrobial activity was evaluated by microtitre plate method. Forsythiaside was found to possess strong antioxidant and antibacterial activity but forsythin was much weaker. Owing to these properties, the study can be further extended to exploit the possible application of forsythiaside as an alternative antioxidant and antibacterial agent of natural origin.