1.How far is the functional cure of chronic hepatitis B from complete cure?
Journal of Clinical Hepatology 2025;41(1):15-23
Functional cure is currently the ideal treatment endpoint for chronic hepatitis B (CHB) in China and globally. HBsAg seroclearance and HBV DNA that cannot be detected in peripheral blood for more than 24 weeks marks the regression of hepatitis B virus (HBV) infection. However, there is still a lack of systematic description of the characteristics of intrahepatic HBV markers after HBsAg seroclearance. This article elaborates on the issues including the latest definition of functional cure, the characteristics of intrahepatic virological markers after HBsAg seroclearance, the significance of ultrasensitive serum HBsAg detection, and antiviral therapy for CHB patients with a low level of HBsAg, so as to improve the understanding of functional cure among clinicians.
2.Quality Evaluation of Zhuye Shigao Granules and Its Therapeutic Effect on Mice with Cold-dampness Pestilence Attacking Lung Syndrome
Haihong LI ; Jiaqi SHEN ; Liwen LIANG ; Ziqi YANG ; Yuting YANG ; Shuyun LIANG ; Zhiliang SUN ; Jiannan LI ; Guangzhi CAI ; Jiyu GONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):182-190
ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules(Zhuye Shigaotang) based on fingerprint and determination of index components, and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography(HPLC), and the methods for determination of total calcium, orientin, isoorientin, ginsenosides Rg1, Re and Rb1 and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group, model group, Zhuye Shigao granules low, medium and high dose groups(9.3, 18.6, 37.2 g·kg-1·d-1), with 10 mice in each group. In addition to the blank group, the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose, while the blank group and model group were given the same volume of normal saline by gavage. Then, the body temperature and organ index of mice in each group were measured, hematoxylin-eosin(HE) staining was used to investigate the lung tissue injury of mice in each group, and enzyme-linked immunosorbent assay(ELISA) was used to detect the changes of tumor necrosis factor-α(TNF-α), interleukin(IL)-lβ, IL-6, IL-10 levels in serum and lung tissue, as well as immunoglobulin(Ig)A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950, and 20 common peaks were calibrated. Seven of them were identified, including peak 11(isoorientin), peak 12(orientin), peak 14(apioside liquiritin), peak 15(liquiritin), peak 17(apioside isoliquiritin), peak 19(isoliquiritin) and peak 20(liquiritigenin). The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows:Total calcium of 9.978-11.294 mg·g-1, isoorientin of 0.033-0.041 mg·g-1, orientin of 0.046-0.055 mg·g-1, ginsenoside Rg1+ginsenoside Re of 0.748-0.762 mg·g-1, ginsenoside Rb1 of 0.151-0.197 mg·g-1, liquiritin of 1.106-1.366 mg·g-1, glycyrrhizic acid of 0.904-1.182 mg·g-1. Compared with the blank group, the body temperature of mice in the model group was significantly increased, the organ indexes of liver, lung and spleen were significantly decreased, the organ index of thymus was significantly increased, HE staining of lung tissue showed infiltration of inflammatory cells, a small amount of serous exudation was observed in the alveoli, and lung tissue was damaged. After the intervention of Zhuye Shigao granules, the pathological changes were improved compared with the model group. The expression levels of IL-1β, IL-6 and TNF-α were significantly increased, the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased(P<0.01). Compared with the model group, the body temperature, the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced(P<0.05, P<0.01). ConclusionIn this study, the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components, and the fingerprint of four herbs(Lophatheri Herba, Ophiopogonis Radix, Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma) in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.
3.Study on mechanism of compound Banlangen Granules for epidemic encephalitis B, hepatitis and parotitis based on UPLC-MS/MS and network pharmacology
Yuwei XIE ; Zhiliang SUN ; Youtian DENG ; Yidong YANG ; Yuan LI ; Baoyi HONG ; Guocheng FU ; Yun WEI ; Haigang CHEN ; Pengfei YANG ; Suyun LU
International Journal of Traditional Chinese Medicine 2024;46(9):1178-1186
Objective:To clarify the transitional components in the blood of compound Banlangen Granules; To explore the mechanism of drugs in the treatment of epidemic encephalitis B, hepatitis and parotitis.Methods:The transitional components in blood of compound Banlangen Granules were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The regulatory targets and pathways of compound Banlangen Granules in the treatment of epidemic encephalitis B, hepatitis and parotitis were analyzed based on UPLC-MS/MS and network pharmacology.Results:A total of 9 blood components were identified, of which 8 were prototype components, including sucrose, o-aminobenzoic acid, uridine, adenosine, guanosine, indole-3-acetonitrile-2 murine-S-β-D-glucopyranoside and salicylic acid. Through network pharmacological analysis, it was concluded that compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.Conclusion:The 9 blood components of compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.
4.Clinical and immunoserological features of 20 cases of epidermolysis bullosa acquisita
Yuan WANG ; Suo LI ; Zhiliang LI ; Ke JING ; Chao SUN ; Guirong LIANG ; Hanmei ZHANG ; Suying FENG
Chinese Journal of Dermatology 2024;57(10):904-909
Objective:To analyze clinical and immunoserological features of patients with epidermolysis bullosa acquisita (EBA) .Methods:Clinical data were collected from patients with confirmed EBA at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to January 2022, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:A total of 20 patients were collected, including 7 males and 13 females, and they were aged 41.85 ± 18.43 years. Ten patients presented with the classical phenotype of EBA, 8 with the inflammatory phenotype of EBA, and 2 with the mixed phenotype of EBA. Mucosal involvement occurred in 19 cases, nail involvement occurred in 4, scarring was observed in 9, and milia in 13. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side in 19 cases. Enzyme-linked immunosorbent assay for type Ⅶ collagen revealed positive results in 19 cases, with a diagnostic sensitivity of 95%. Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 290 000 in 16 cases, with a diagnostic sensitivity of 80%, and multiple autoantibodies against different basement membrane zone antigens were identified in 3 cases. Fifteen patients received systemic glucocorticoids, including 2 receiving combined immunosuppressive agents and 13 receiving combined anti-inflammatory agents with dapsone and colchicine as the first and second commonly used anti-inflammatory agents respectively; among 5 patients receiving non-glucocorticoid therapy, 2 with inflammatory EBA were sensitive to dapsone and colchicine, while the other 3 patients were lost to follow-up. Totally, 17 patients were followed up for an average duration of 26.21 months. Among the 17 patients, 1 achieved complete remission off therapy, 2 achieved complete remission on minimal therapy, and the remaining 14 patients achieved partial remission.Conclusions:The treatment of EBA is challenging, and anti-inflammatory agents such as dapsone and colchicine are often used. Immunoserological tests are of great value in the diagnosis of EBA.
6.Research advances in interferon-stimulated genes in treatment of hepatitis B virus infection
Yunwen LIAN ; Xingrong ZHENG ; Hewei WU ; Zhiliang GAO ; Xiyao CHEN ; Chan XIE
Journal of Clinical Hepatology 2022;38(1):180-186
Hepatitis B virus (HBV) infection is closely associated with the adverse events such as liver cirrhosis, liver cancer, and liver failure and remains a serious threat to human health. Pegylated interferon is an indispensable drug for the treatment of chronic hepatitis B (CHB), and interferon-stimulated genes are associated with a variety of viruses, but few studies have mentioned their association with hepatitis B and their predictive effect after the treatment of hepatitis B with interferon. This article introduces the predictive factors for interferon treatment of CHB and summarizes the association of interferon-stimulated genes with hepatitis B and their predictive effect, so as to provide a reference for clinical work and basic research.
7.Anti-HBV therapy timing and drug selection in various populations
Yeqiong ZHANG ; Qiumin LUO ; Lu WANG ; Liang PENG ; Zhiliang GAO
Journal of Clinical Hepatology 2022;38(11):2444-2447
Hepatitis B virus (HBV) infection is still a serious disease threatening human health. Anti-HBV treatment is an extremely important means to reduce the threat of hepatitis B. In recent years, there has been no consensus on the timing and drug selection of anti-HBV therapy. The timing and drug selection of anti-HBV therapy in various populations are discussed in this article.
8.Clinical and immunoserological features of 7 cases of anti-p200 pemphigoid
Yuan WANG ; Zhiliang LI ; Suo LI ; Ke JING ; Chao SUN ; Guirong LIANG ; Hanmei ZHANG ; Suying FENG
Chinese Journal of Dermatology 2022;55(7):557-561
Objective:To analyze clinical and immunoserological features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid in Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to October 2021, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:Seven patients with anti-p200 pemphigoid were included. Indirect immunofluorescence on salt-split skin (IIF-SSS) showed that serum IgG antibodies of the 7 patients were located in the dermis of the salt-split skin, and Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 200 000. Four patients presented with classic bullous pemphigoid-like skin lesions, 2 initially presented with eczematous lesions, and 1 presented with linear IgA bullous dermatosis-like skin lesions. Circulating IgG antibodies could recognize the recombinant laminin γ1 C-terminal region in 6 cases. Four patients received different doses of systemic glucocorticoids, 1 of whom was resistant to high-dose systemic glucocorticoids (equivalent to 1.4 mg·kg -1·d -1 prednisone) ; 2 responded well to minocycline and dapsone; 1 was lost to follow-up. Four patients achieved complete remission and discontinued the treatment at a mean follow-up of 22.5 months; 2 received complete remissiona on minimal therapy at a mean follow-up of 8 months. Conclusion:Patients with anti-p200 pemphigoid presented with heterogeneous clinical manifestations, and the recombinant C-terminal fragment of laminin γ1 can serve as a reliable antigen substrate for the detection of autoantibodies in patients with anti-p200 pemphigoid; some patients can eventually achieve complete remission off treatment.
9.Whole-genome sequencing and analysis of the Chinese herbal plant .
Yisong LIU ; Qi TANG ; Pi CHENG ; Mingfei ZHU ; Hui ZHANG ; Jiazhe LIU ; Mengting ZUO ; Chongyin HUANG ; Changqiao WU ; Zhiliang SUN ; Zhaoying LIU
Acta Pharmaceutica Sinica B 2020;10(2):374-382
Background:
() (2n = 2x = 16) is genus of flowering plants belonging to the Gelsemicaeae family.
Method:
Here, a high-quality genome assembly using the Oxford Nanopore Technologies (ONT) platform and high-throughput chromosome conformation capture techniques (Hi-C) were used.
Results:
A total of 56.11 Gb of raw GridION X5 platform ONT reads (6.23 Gb per cell) were generated. After filtering, 53.45 Gb of clean reads were obtained, giving 160 × coverage depth. The genome assemblies 335.13 Mb, close to the 338 Mb estimated by k-mer analysis, was generated with contig N50 of 10.23 Mb. The vast majority (99.2%) of the assembled sequence was anchored onto 8 pseudo-chromosomes. The genome completeness was then evaluated and 1338 of the 1440 conserved genes (92.9%) could be found in the assembly. Genome annotation revealed that 43.16% of the genome is composed of repetitive elements and 23.9% is composed of long terminal repeat elements. We predicted 26,768 protein-coding genes, of which 84.56% were functionally annotated.
Conclusion
The genomic sequences of could be a valuable source for comparative genomic analysis in the Gelsemicaeae family and will be useful for understanding the phylogenetic relationships of the indole alkaloid metabolism.
10.The value of ENO1 autoantibodies and CEA combination in the diagnosis of lung adenocarcinoma
Nan SUN ; Shouguo SUN ; Ruochuan ZANG ; Zhiliang LU ; Jie HE
Chinese Journal of Laboratory Medicine 2018;41(6):446-449
Objective To study the differential diagnostic efficacy of α-enolase ( ENO1 ) autoantibodies in lung adenocarcinoma , benign pulmonary disease , and normal individuals , and to evaluate the improvement of the diagnostic efficiency of existing markers by establishing a binary logistic regression model.Methods This was a case-control study.Participants were from the public health welfare program led by the National Cancer Center/Chinese Academy of Medical Sciences Peking Union Medical College Cancer Hospital.Serum samples were collected June 2014 to June 2017 including 60 patients with lung adenocarcinoma , 50 patients with benign lung diseases , and 90 healthy controls.Luminex MAGPIX platform was applied to detect serum ENO1 autoantibodies, CEA and Cyfra21-1 proteins.The receiver operating characteristic curve (ROC)analysis and binary logistic regression were used to evaluate the performance and build diagnostic model.Results The median level of serum ENO1 autoantibody in patients with lung adenocarcinoma was 918.5 ( 665.5-2 043.3 ), which was significantly higher than that in the normal individuals (722.5, 585.5-921.8, Z=-3.113, P=0.002) and benign lung disease patients (693.0, 501.4-973.3, Z=-3.395, P=0.001).And no significant differences between benign disease groups and normal individuals (Z=-1.155, P=0.248).ROC was plotted, and the area under the curve (AUC) of ENO1 autoantibodies was 0.664 (95% confidence interval : 0.576-0.752), while the AUCs of existing diagnostic marker CEA and Cyfra21-1 were 0.680 (95% confidence interval : 0.594-0.767) and 0.617 (95% confidence interval: 0.532-0.703).A joint diagnostic model including ENO1 and CEA was built with an AUC of 0.757 (95%confidence interval : 0.675-0.838).The diagnostic efficacy of the model was significantly different from ENO1 autoantibodies (Z=2.648, P=0.008).When the specificity was 90%, the sensitivity of ENO1 autoantibodies was 38.3%, while the sensitivity of the combination with CEA was raised to 50%.Conclusion ENO1 autoantibodies could be a marker for the auxiliary diagnosis of lung adenocarcinoma, and can improve the efficacy of the existing diagnostic markers such as CEA .ENO1 has the potential use for the diagnosis and screening.

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