HBx Mediated Increase of DDX17 Contributes to HBV-Related Hepatocellular Carcinoma Tumorigenesis.

HBV is strongly associated with HCC development and DEAD-box RNA helicase 17 (DDX17) is a very important member of the DEAD box family that plays key roles in HCC development by promoting cancer metastasis. However, the important role of DDX17 in the pathogenesis of HBV-related HCC remains unclear. In this study, we investigated the role of DDX17 in the replication of HBV and the development of HBV-associated HCC. Based on data from the GEO database and HBV-infected cells, we found that DDX17 was upregulated by the HBV viral protein X (HBx). Mechanistically, increased DDX17 expression promoted HBV replication and transcription by upregulating ZWINT. Further study showed that DDX17 could promote HBx-mediated HCC metastasis. Finally, the promotive effect of DDX17 on HBV and HBV-related HCC was confirmed in vivo. In summary, the results revealed the novel role of DDX17 in the replication of HBV and the metastasis of HBV-associated HCC.

SIRT2 Promotes HBV Transcription and Replication by Targeting Transcription Factor p53 to Increase the Activities of HBV Enhancers and Promoters.

Chronic hepatitis B (CHB) virus infection is one of the leading causes of cirrhosis and liver cancer. Although the major drugs against CHB including nucleos(t)ide analogs and PEG-interferon can effectively control human hepatitis B virus (HBV) infection, complete cure of HBV infection is quite rare. Targeting host factors involved in the viral life cycle contributes to developing innovative therapeutic strategies to improve HBV clearance. In this study, we found that the mRNA and protein levels of SIRT2, a class III histone deacetylase, were significantly upregulated in CHB patients, and that SIRT2 protein level was positively correlated with HBV viral load, HBsAg/HBeAg levels, HBcrAg, and ALT/AST levels. Functional analysis confirmed that ectopic SIRT2 overexpression markedly increased total HBV RNAs, 3.5-kb RNA and HBV core DNA in HBV-infected HepG2-Na+/taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, SIRT2 silencing inhibited HBV transcription and replication. In addition, we found a positive correlation between SIRT2 expression and HBV RNAs synthesis as well as HBV covalently closed circular DNA transcriptional activity. A mechanistic study suggested that SIRT2 enhances the activities of HBV enhancer I/HBx promoter (EnI/Xp) and enhancer II/HBc promoter (EnII/Cp) by targeting the transcription factor p53. The levels of HBV EnI/Xp and EnII/Cp-bound p53 were modulated by SIRT2. Both the mutation of p53 binding sites in EnI/Xp and EnII/Cp as well as overexpression of p53 abolished the effect of SIRT2 on HBV transcription and replication. In conclusion, our study reveals that, in terms of host factors, a SIRT2-targeted program might be a more effective therapeutic strategy for HBV infection.

KAT2A Promotes Hepatitis B Virus Transcription and Replication Through Epigenetic Regulation of cccDNA Minichromosome.

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Sufficient maintenance of the HBV covalently closed circular DNA (cccDNA), which serves as a template for HBV transcription, is responsible for the failure of antiviral therapies. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation and methylation of cccDNA-bound histone 3 (H3) and histone 4 (H4), the potential contributions of histone succinylation and related host factors remain obscured. Here, by screening a series of succinyltransferases and desuccinylases, we identified KAT2A as an important host factor of HBV transcription and replication. By using HBV-infected cells and mouse models with HBV infection, KAT2A was found to affect the transcriptional activity of cccDNA but did not affect cccDNA production. Mechanism studies showed that KAT2A is mainly located in the nucleus and could bind to cccDNA through interaction with HBV core protein (HBc). Moreover, we confirmed histone H3K79 succinylation (H3K79succ) as a histone modification on cccDNA minichromosome by using the cccDNA ChIP-Seq approach. Importantly, KAT2A silencing specifically reduced the level of cccDNA-bound succinylated H3K79. In conclusion, KAT2A promotes HBV transcription and replication through epigenetic machinery, and our findings may provide new insight into the treatment of HBV infection.

[Association of Glucose Variability and ICU Delirium of Patients after Liver Transplantation].

OBJECTIVE: To study the association of glucose variability and ICU delirium of patients after liver transplantation. METHODS: This was a retrospective, single-center cohort study. Patients who admitted to ICU after liver transplantation during Aug. 2016 to Dec. 2018 were enrolled. They were divided into two groups accoding to whether they had delirium in ICU. Multivariate logistic regression analysis model was used to analyze the relationship between glucose variability and ICU delirium, and Cochran-Armitage trend test was used to analyze the linear relationship between blood glucose variability levels and the incidence of delirium. RESULTS: A total of 242 patients were enrolled, among them, 36 patients had delirium. The occurrence rate of delirium was 14.9% (36/242). Results indicated that glucose variability was an independently risk factor of ICU delirium for liver transplant patients ( P=0.045), and delirium was more common in patients with higher glucose variability (fourth quartile vs. first quartile, odds ratio =5.283, 95% confidence interval: 1.092～25.550, P=0.038). Results of Cochran-Armitage trend test indicated that there was a linear relationship between blood glucose variability level and ICU delirium rate, with the increase of glucose variability level, the risk of ICU delirium was increased too ( P<0.001). CONCLUSION: Glucose variability was an independently risk factor of ICU delirium in liver transplantation patients.

[Clinical efficacy of Bushen Huoxue Anshen therapy in treating perimenopausal sleep disorder with kidney deficiency and blood stasis].

The efficacy and safety of traditional Chinese medicine and acupuncture in the treatment of kidney-deficiency and bloodstasis perimenopausal sleep disorders were evaluated. A total of 67 subjects who completed the study were randomly divided into two groups. The traditional Chinese medicine group was orally given Bushen Huoxue Anshen Fang,and the acupuncture group was given acupuncture treatment. Both groups were treated for three consecutive courses of treatment,with a course of treatment of 30 days. The changes of PSQI score,improved Kupperman score,TCM syndromes,serum sex hormone,coagulation,routine blood and urine,liver and kidney function and electrocardiogram were observed before and after treatment. After treatment,the total effective rates of Chinese medicine group and acupuncture group were similar or respectively 91. 43% and 87. 50%. The scores of PSQI,improved Kupperman and TCM syndromes in both groups decreased significantly( P<0. 05). The effect of improving Kupperman score in TCM group was better than that in acupuncture group( P< 0. 01). The effect of improving PSQI and TCM syndromes was similar to that in acupuncture group. The levels of serum FSH and LH were decreased in both groups( P<0. 05),but with no significant difference between the two groups; the level of serum E2 was increased in both groups,but with no significant difference. Compared with before treatment,PT was increased in traditional Chinese medicine group( P<0. 05),but with no significant difference in APTT,TT and FIB before and after treatment; PT and TT were prolonged in acupuncture group( P<0. 05),but with no significant difference in APTT and FIB before and after treatment. The effect of improving PT and TT in the acupuncture group was better than that in the traditional Chinese medicine group( P<0. 05). The results showed that TCM and acupuncture had similar therapeutic effects on perimenopausal sleep disorder of kidney deficiency and blood stasis type,and were safe and reliable. The mechanism was related to the improvement of serum FSH and E2 levels.

[Application of kidney deficiency and blood stasis and disharmony between heart and kidney theories in patients with sleep disorders in perimenopause].

Perimenopausal syndrome refers to a series of physical and mental symptoms, caused by the fluctuation of the sex hormones in the menopause, which is one of the common diseases in gynecology. The incidence of sleep disorders in perimenopausal women is increasing significantly. Both Chinese medicine and Western medicine are trying to exploring its pathologic mechanism to find the safe and effective methods of treatment. Menopausal sleeping disorder is the same as the perimenopause syndrome and insomnia category in traditional Chinese medicine. Kidney deficiency is the basic characteristic of perimenopause, whether kidney essence, kidney Qi, kidney Yin or kidney Yang can lead to blood stasis. It is believed that this disease results from kidney deficiency in the root and blood stasis in the tip, and on this basis women affected by many factors will result in disharmony between heart and kidney. In clinical practice, The method of tonifying kidney and activating blood applied to treat perimenopause syndrome with insomnia was testified to be effective. Therefore the author thought that kidney deficiency and blood stasis and disharmony between heart and kidney were the key factors of patients with insomnia in perimenopause.

[Features of Professor Ma Kun's medication in treating ovulatory infertility].

In order to analyze Professor Ma Kun's medication in treating anovulatory infertility, her prescriptions for treating anovulatory infertility in 2012-2015 were collected. The medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system, association rules, complex system entropy clustering and other mining methods. Finally, a total of 684 prescriptions and 300 kinds of herbs were screened out, with a total frequency of 11 156 times; And 68 core combinations and 8 new prescriptions were mined. The top three frequently used herbs by effect were respectively tonic herb, blood circulation promoting herb, and Qi-circulation promoting herb. The top three tastes were sweetness, bitterness and pungent flavor. The results showed 28 herbs with a high frequency of ≥100.The top 10 frequently used herbs were respectively Angelica Sinensis Radix, Cyperi Rhizoma, Chuanxiong Rhizome, Paeoniae Radix Rubra, Cyathulae Radix, Taxilli Herba, Cuscutae Semen, Codonopsis Radix, Ligustri Lucidi Fructus, Paeoniae Albaand Paeoniae Radix Alba. The association rules analysis showed commonly used herbal pairs, including Rehmanniae Radix Preparata-Chuanxiong Rhizome, Rehmanniae Radix Preparata-Angelica Sinensis Radix, Cuscutae Semen-Dipsaci Radix. In conclusion, Professor Ma has treated anovulatory infertility by nourishing the kidney and activating blood throughout the treatment course, and attached the importance to the relationship between Qi and blood and there gulation of liver, spleen and kidney in treating anovulatory infertility.

Piperidine alkaloids from Chinese mangrove Sonneratia hainanensis.

A new diphenacyl-piperidine alkaloid, sonneratine A (2), identified as a piperidine ring bearing two phenacyl substitutes at C-2 and C-6, and a known related derivative, (+/-)1-(2-piperidyl)-4-( P-methoxyphenyl)-butanone-2 (3), were isolated from the leaves and stems of the Hainan mangrove Sonneratia hainanensis. The structure of the new compound was determined by extensive analysis of its spectroscopic data and by comparison of its NMR data with those reported in the literature.

Diastereoisomeric macrocyclic polydisulfides from the mangrove Bruguiera gymnorrhiza.

The uncommon macrocyclic polydisulfides, trans-3,3'-dihydroxy-1,5,1',5'-tetrathiacyclodecane (1), cis-3,3'-dihydroxy-1,5,1',5'-tetrathiacyclodecane (2), along with five known related cyclic disulfides, gymnorrhizol (3), neogymnorrhizol (4), bruguiesulfurol (5), brugierol (6), and isobrugierol (7), were isolated from the mangrove Bruguiera gymnorrhiza collected from Guangdong Province, China. Structures of compounds 1 and 2 were determined by extensive analysis of their spectroscopic data, by comparison of their NMR spectroscopic data with those of the co-occurring known compounds, as well as by single-crystal X-ray diffraction analysis. A possible biogenetic origin was also proposed.

[Tiaohe Ganpi Hexin Decoction in treatment of irritable bowel syndrome with diarrhea: a randomized controlled trial].

BACKGROUND: The quality of life has been greatly influenced and the cost of medical expenses is very high in patients with irritable bowel syndrome (IBS). The etiology and pathogenesis of IBS are still unclear, and the prevention and treatment of this disease still lack of effective methods. OBJECTIVE: To explore and analyze the effects of Tiaohe Ganpi Hexin Decoction (TGHD), a compound traditional Chinese herbal medicine for regulating the liver and spleen, on IBS patients with diarrhea. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: All 40 IBS patients came from the First Hospital of Jinan University, Guangzhou Red Cross Hospital, and the First Affiliated Hospital of Guangzhou University of Chinese Medicine, and were randomly divided into two groups. Patients in the treatment group (n=20) were given TGHD, while those in the control group (n=20) were prescribed oral pinaverium with a four-week treatment period. MAIN OUTCOME MEASURES: Traditional Chinese medicine (TCM) syndrome score, total obviously effective rate, disappearance rate of symptoms, and clinical symptom score in the two groups were evaluated before and after four-week treatment. RESULTS: After the treatment, TCM syndrome scores in both groups were decreased (P<0.01), and the TCM syndrome score in the treatment group was significantly lower than that in the control group (P<0.01). There was a significant difference in the total obviously effective rate between the two groups (P<0.01), and the total obviously effective rates in the treatment and control groups were 85%(17/20) and 45%(9/20) respectively. The disappearance rates of abdominal pain, abdominal distention, poor stool output, stool frequency, stool character and mucous stool in the treatment group were higher than those in the control group (P<0.05). The symptom scores of abdominal pain, abdominal distention, poor stool output, stool frequency, stool character and mucous stool in the treatment group were lower than those in the control group (P<0.05). CONCLUSION: TGHD can significantly improve the clinical symptoms in IBS patients with diarrhea.

Flavonoid constituents from Spiranthes australis LINDL.

Chemical investigation of the whole plant of Spiranthes australis (R. BROWN) LINDL. resulted in the isolation and characterization of three new flavonoid constituents, 5-hydroxy-4'-[(2-isopentenyl)oxy]-3,7,3'-trimethoxyflavone (1), 3-O-[[O-beta-D-xylopyranosyl]-(1-->2)-beta-D-glucopyranosyl]-8-(p-hydroxy-benzyl)-kaempferol (2) and 3-O-[O-[2-O-(E)-p-coumaroyl-beta-D-xylopyranosyl]-(1-->2)-beta-D-glucopyranosyl]-8-(p-hydroxy-benzyl)-kaempferol (3), together with six known flavonoid compounds. The structures of new compounds were determined on the basis of spectroscopic analysis, including HR-ESI-MS, 1D- and 2D-NMR techniques and chemical methods.

A new flavanoid from the whole plant of Spiranthes australis (R. Brown) Lindl.

A new flavonoid was isolated from the whole plant of Spiranthes australis (R. Brown) Lindl (Orchidacea). Its structure was characterized as 3,7-dimethoxy-5-hydroxy-2-([4-(3-methyl-2-butenyl)oxy]phenyl)-4H-1-benzopyran-4-one on the basis of chemical and spectral evidence including 2D NMR analysis.