Distinct common signatures of gut microbiota associated with damp-heat syndrome in patients with different chronic liver diseases.

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are prevalent in China. According to traditional Chinese medicine (TCM) theory, damp-heat (DH) syndrome is common in chronic liver disease. However, the biological characteristics related to quantitative diagnosis remain to be determined. This study aimed to identify the consistent alterations in the gut microbiota associated with DH syndrome in patients with CHB or NAFLD. Methods: A total of 405 individuals were recruited, of which 146 were participants who met the consistent TCM diagnosis by three senior TCM physicians and were typical syndromes. All participants were required to provide fresh stool and serum samples. The gut microbiota was assessed by fecal 16S rRNA gene sequencing, and the serum metabolite profiles of participants were quantified by an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. DH syndrome-related bacteria taxa were identified based on the 146 individuals with typical syndromes and validated in all 405 volunteers. Results: The results showed that CHB and NAFLD patients with typical TCM DH syndrome had consistently elevated serum total bile acid (TBA) levels. Significant alterations in microbial community were observed according to TCM syndromes identification. A total of 870 microbial operational taxonomic units and 21 serum metabolites showed the same variation trends in both the CHB and NAFLD DH syndrome groups. The functional analysis predicts consistent dysregulation of bile acid metabolism. Five genera (Agathobacter, Dorea, Lachnospiraceae_NC2004_group, Subdoligranulum, and unclassified_c__Clostridia) significantly decreased in abundance in patients with DH syndrome. We utilize these five genera combined with TBA to construct a random forest classifier model to predict TCM diagnosis. The diagnostic receiver-operator characteristic (ROC) areas for DH syndrome were 0.818 and 0.791 in internal tenfold cross-validation and the test set based on all 405 individuals, respectively. Conclusion: There are common signatures of gut microbiota associated with DH syndrome in patients with different chronic liver diseases. Serum TBA combined with DH-related genera provides a good diagnostic potential for DH syndrome in chronic liver disease.

Comparison of the clinical features and therapeutics of COVID-19 in cardio-cerebrovascular disease (CCVD) and non-CCVD patients.

Cardio-cerebrovascular disease (CCVD) is a major comorbidity of Coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO2 were lower in the CCVD group. Although no statistical difference was observed in the outcomes between groups, CCVD patients received more intensive comprehensive treatment to improve COVID-19 symptoms compared with non-CCVD patients. Integrated Chinese and Western medicine treatments have certain advantages in controlling the severe conversion rate and mortality of COVID-19. In addition, given that COVID-19 patients are usually related to coagulation disorders and thrombosis risk, the application of Chinese medicine in promoting blood circulation and removing stasis should be strengthened.

[Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients].

OBJECTIVE: To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy. METHODS: Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared. RESULTS: Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both). CONCLUSIONS: Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.

[Study on the correlation between chronic asymptomatic HBV carriers of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles].

OBJECTIVE: To study on the correlation between chronic asymptomatic HBV carriers (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles. METHODS: Totally 105 ASC were assigned to two groups according to their constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined using PCR-SSP. RESULTS: The gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia group than in the non-yin asthenia group (being 27.8% and 39.7%, P < 0.05). The gene frequency of HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele were obviously higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin asthenia group (4.3% and 9.5%), showing statistical difference (P < 0.05, P < 0.01). CONCLUSIONS: HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele might be the molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients with ASC.

[The effect of extract of ginkgo biloba leaf during the formation of HBV-related hepatocellular carcinoma].

OBJECTIVE: To investigate the effect of extract of ginkgo biloba leaf (EGb) during the formation of HBV-related hepatocellular carcinoma (HCC). METHODS: 99 HBV transgenic mice were randomly divided into control group, high-dose group, low-dose group. High-dose group and low-dose group were intraperitoneal injected 35mg/(kg x d) and 17.5 mg/(kg x d) of the shuxuening injection. Control group without special treatment. The serological markers and immunohistochemical markers in liver tissue will be done at the first 12 months and 18 months. RESULTS: (1) HBV transgenic mice can be found HCC at the 18 months. The incidence of HCC was lower in high-dose group and low-dose group, there was statistically different among the three groups. (2) The semi-quantitative scoring of liver HBx expression was highest in the control group at the 12 months. The semi-quantitative scoring of liver HBx, p53 and Bcl-2 expression was highest in the control group at the 18 months. They all appeared statistically different among the three groups. (3) Spearman correlation analysis showed that HCC incidence and liver tissue HBx, p53, Bcl-2 expression was a certain degree of positive correlation, r was 0.536, 0.487 and 0.403, P < 0.05. CONCLUSION: EGb can reduced the incidence of the HCC with HBV transgenic mice. The reason may be that the EGb can reduce liver HBx, p53, Bcl-2 protein expression in the HBV transgenic mice.

[Association of chinese medicine constitution and human leukocyte antigen-DQA1 gene polymorphism with outcomes of hepatitis B virus infection].

OBJECTIVE: To observe the Chinese medicine constitution types and human leukocyte antigen (HLA)-DQA1 gene polymorphism in patients with hepatitis B (HB) virus infection in Chinese Han population of Zhejiang Province, for exploring the roles of constitution factor in pathogenesis of HB. METHODS: A total of 240 subjects, including 120 biopsy-proven chronic HB (CHB), 60 HB asymptomatic carrier (ASC) and 60 resolved from HBV infection spontaneously (RHBS) were studied. Their Chinese medicine constitution type was judged by Wangqi's classification, and their genotype of HLA-DQA1 was detected by polymerase chain reaction sequence specific primer for comparing the difference between groups in distribution frequency (DF) of constitution types and genes. RESULTS: (1) As compared with the RHBS group, DF of yin-deficiency constitution and phlegm-dampness constitution in the CHB group was significant higher (20.0% vs. 6.7% and 12.5% vs. 1.7%), and that of placid constitution was significant lower (11.7% vs. 31.7%), showing statistical significance between groups (OR = 3.5, 95% CI: 1.16-10.60; OR = 8.4, 95% CI: 1.09-65.42; OR = 0.161, 95% CI: 0.076-0.34; all P < 0.05). (2) As compared with the ASC group, DF of damp-heat constitution was significant higher (24.2% vs. 6.7%, P < 0.05, OR = 4.462, 95% CI: 1.49-13.36), and that of placid constitution was significant lower (11.7% vs. 45.0%, P < 0.01, OR = 0.285, 95% CI: 0.13-0.62) in the CHB group. (3) As compared with RHBS group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 5.8%, P < 0.01, OR = 10.04, 95% CI: 4.48-22.48); and that of HLA-DQA1 * 0102 allele was significant lower (9.6% vs. 36.7%, P < 0.01, OR = 0.183, 95% CI: 0.10-0.32). (4) As compared with ASC group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 7.5%, P < 0.01, OR = 7.667, 95% CI: 3.7-15.87), and that of HLA-DQA1 * 0102 allele was significant lower (20.0% vs. 9.6%, P < 0.01, OR = 0.424, 95% CI: 0.23-0.79). CONCLUSION: Both Chinese medicine constitution and HLA-DQA1 gene polymorphism show connection with the outcomes of HB virus infection in Chinese Han population, but the real association between them is required for further study.