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The Chinese herbal formula TiaoGanYiPi (TGYP) showed effective against chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection. Hence, we aimed to clarify the mechanisms and potential targets between TGYP and CHB. The active compounds and related putative targets of TGYP, and disease targets of CHB were obtained from the public databases. The key targets between TGYP and CHB were identified through the network construction and module analysis. The expression of the key targets was detected in Gene Expression Omnibus (GEO) dataset and normal hepatocyte cell line LO2. We first obtained 11 key targets which were predominantly enriched in the Cancer, Cell cycle and HBV-related pathways. And the expression of the key targets was related to HBV infection and liver inflammation verified in GSE83148 database. Furthermore, the results of real-time quantitative PCR and CCK-8 assay indicated that TGYP could regulate the expression of key targets including CCNA2, ABL1, CDK4, CDKN1A, IGFR and MAP2K1, and promote proliferation of LO2 cells. In coclusion, we identified the active compounds and key targets btween TGYP and CHB, and found that the TGYP might exhibite curative effect on CHB via promoting hepatocyte proliferation and inhibiting the liver inflammatory processes.

BACKGROUND: Hepatocellular carcinoma is the world’s leading cause of cancer-related death. Chronic hepatitis B virus and hepatitis C virus infection cause liver cancer. The aim of this study was to investigate the relationship between statins and the risk of hepatocellular carcinoma in patients with hepatitis B or C. METHODS: We systematically searched Web of Science, Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database from their inception to January 2019. We included studies that reported the hepatocellular carcinoma incidence among hepatitis B virus- or hepatitis C virus-infected patients or hepatitis B virus- or hepatitis C virus-related cirrhotic patients, evaluated and clearly defined exposure to statins, provided effective comparison groups, and reported risk estimates. Inclusion was not otherwise restricted. Summary relative risk estimates with 95% CIs were calculated using a random-effects model. RESULTS: Meta-analysis of 10 studies showed that statin users had a significantly lower risk of hepatocellular carcinoma (relative risk = 0.47, 95% CI = 0.38-0.56) with significant heterogeneity. In 7 hepatitis studies, using statin was associated with a 53% reduction in the incidence of hepatocellular carcinoma (relative risk = 0.47, 95% CI = 0.43-0.50) with substantial heterogeneity. In 3 cirrhosis studies, the incidence of hepatocellular carcinoma in statin users was significantly reduced by 55% (relative risk = 0.45, 95% CI = 0.30-0.61) with no heterogeneity. CONCLUSION: Statins reduce the hepatocellular carcinoma risk among patients infected with hepatitis B virus or hepatitis C virus. This chemoprotective association is more pronounced in hepatitis B virus or hepatitis C virus-associated cirrhotic patients.

To explore the mechanism through which liver cirrhosis (LC) causes erectile dysfunction (ED). Bioinformatic analysis was used to predict the potential signalling pathways in LC-induced ED, and N-nitrosodiethylamine was used to establish a rat model of LC. HE staining, Western blotting and RT-qPCR were used to detect pathological tissue damage and changes in mRNA and protein expression levels. In addition, the expression levels of sex hormones such as estradiol (E2), prolactin (PRL) and testosterone (T) were measured. The hypoxia-inducible factor (HIF) pathway was an important pathway in our bioinformatics prediction. Pathological damages were detected in the liver and penile tissues of the model rats. Compared with the normal group's serum hormone levels, E2 and PRL were increased in LC rats, while T was decreased (p 0.01). The mRNA and protein expression results from penis tissues showed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were both downregulated, and HIF-1α was upregulated in the model group compared to the normal group (p 0.01). These data suggest that LC hinders erectile function and causes histopathological changes in the penis by affecting the expression of HIF-1α, eNOS, iNOS, E2, PRL and T.

Background The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. Purpose We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. Study design Living evidence-based guideline. Methods This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. Results The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. Conclusion This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

The purpose of this study was to clarify the expression pattern of Nek2B in hepatocellular carcinoma (HCC) and its influence on malignant phenotypes of HCC through regulating SFRP1 and the Wnt/β-catenin pathway.Nek2B levels in 64 paired HCC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between Nek2B level and clinical parameters of HCC patients was analyzed. Regulatory effects of Nek2B and SFRP1 on clonality, proliferation and apoptosis of MHCC97H and Hep3B cells were determined through functional experiments. Western blot was conducted to detect protein levels of SFRP1, β-catenin, c-myc, cyclinD1 and MMP7 in HCC cells with overexpression or knockdown of Nek2B. At last, rescue experiments were performed to clarify the role of Nek2B/SFRP1 regulatory loop in aggravating the progression of HCC.Nek2B was upregulated in HCC tissues and cells. HCC patients expressing a high level of Nek2B were in more advanced tumor stage and had worse prognosis. Overexpression of Nek2B in MHCC97H cells enhanced clonality, 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio and suppressed apoptosis. Besides, knockdown of Nek2B in Hep3B cells yielded the opposite results. SFRP1 was downregulated in HCC, and low level of SFRP1 predicted worse prognosis of HCC. Overexpression of Nek2B downregulated SFRP1, but upregulated β-catenin, c-myc, cyclinD1 and MMP7 in HCC cells. Importantly, Nek2B/SFRP1 regulatory loop was identified to aggravate the progression of HCC.Nek2B is upregulated in HCC, and closely linked to tumor stage and poor prognosis in HCC patients. Through interaction with SFRP1, Nek2B aggravates the progression of HCC by activating the Wnt/β-catenin pathway.

Background The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. There have been reports that long-term SARS-CoV-2 RNA shedding and re-infection of COVID-19 patients existed. However, the specific mechanism, diagnosis, and treatment of COVID-19 are still unclarified. Case presentation In this case, we reported a 64-year-old patient who had a long-term course of COVID-19 for 174 days with two retests of SARS-CoV-2 RNA positive after discharging from the hospital. The patient’s serum immunoglobulin G (IgG) of SARS-CoV-2 tested positive after the initial infection. And during treatment, the CD4 + T cell count and ratio to peripheral blood mononuclear cell (PBMC) were in dynamic change. Conclusions Our results suggested that the host immune system responded with IgG production after SARS-CoV-2 infection, but was not protective enough for the patient. The reemergence of SARS-CoV-2 could be related to the cell count and proportion of CD4 + T cells in PBMC. And the increase of CD4 + T cells after treatment may help to clear the virus.

The Chinese herbal formula Tiao-Gan-Yi-Pi (TGYP) showed effective against Chronic Hepatitis B (CHB). In this study, we aimed to clarify the mechanisms and potential targets between TGYP and CHB through network pharmacology and molecular docking verification. The compounds of TGYP were identified in the TCMSP and CNKI databases, and their putative targets were predicted through SwissTargetPrediction and STITCH databases. The targets of CHB were obtained from the GeneCards, NCBI Gene, and DisGeNET databases. The above mentioned data were visualized using Cytoscape, and molecular docking showed the relationship between them. The expression of key targets was verified in GEO databases. Hence, we screened out 11 TGYP-related key targets for CHB included ABL1, CASP8, CCNA2, CCNB1, CDK4, CDKN1A, EP300, HIF1A, IGF1R, MAP2K1 and PGR. The key targets were predominantly enriched in the cancer, cell cycle and hepatitis B pathways and involved in the positive regulation of fibroblast proliferation, signal transduction, and negative regulation of gene expression biological processes, and expression of key target genes was related to HBV infection and liver inflammation. Through this newly constructed interaction network between TGYP and CHB, we identified active compounds and targets which could be further used for providing clinical guidance.

Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9–43.2%) in the experiment group and 27.21% (95% CI 22.0–32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4–12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

BackgroundNucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal.Methods/designThe study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120 weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5 mg per day for consolidation therapy for 96 weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5 mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24 weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial.ConclusionThis study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population.Trial registrationChinese Clinical Trial Registry No.ChiCTR1900021232. Registered on February 2, 2019

It is the great priority to detect colorectal cancer (CRC) as early as possible, finally to reduce the incidence and mortality of CRC. However, although colonoscopy is recommended in many consensuses, yet no one systematic review is conducted to figure out how colonoscopy could change the incidence and mortality. In our study, we conducted a comprehensive meta-analysis to evaluate the association between colonoscopy screening and the incidence or mortality of CRC. PubMed, EMBASE, and PMC database were systematically searched from their inception to June 2020. A total of 13 cohort and 16 case-control studies comprising 4,713,778 individuals were obtained in this review. Our results showed that colonoscopy was associated with a 52% RR reduction in incidence of CRC (RR: 0.48, 95% CI: 0.46-0.49) and 62% RR reduction in mortality of CRC (RR: 0.38, 95% CI: 0.36-0.40). Subgroup analysis of different interventions, study design, country, sample size, age or sex showed that the incidence and mortality reduction remained consistent, and colonoscopy screening had the same effect on people below and above 50. Our study indicated that colonoscopy could significantly reduce the incidence and mortality of CRC.

Objective Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold. Methods Medline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20-100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC). Results We retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31-0.34) and 0.99 (95%CI 0.98-0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47-0.50) and 0.98 (95%CI 0.97-0.99), respectively. Forty-six studies with AFP threshold of 20-100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60-0.62) and 0.86 (95%CI 0.86-0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20-100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound. Conclusion AFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.

To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue (调肝健脾和血) and Tiaogan Jiedu Huashi (调肝解毒化湿) fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P

Early and accurate diagnosis of liver fibrosis is necessary for HBeAg-positive chronic hepatitis B (CHB) patients with normal or slightly increased alanine aminotransferase (ALT), Liver biopsy and many non-invasive predicting markers have several application restrictions in grass-roots hospitals. We aimed to construct a non-invasive model based on routinely serum markers to predict liver fibrosis for this population. A total of 363 CHB patients with HBeAg-positive, ALT ≤2-fold the upper limit of normal and liver biopsy data were randomly divided into training (n = 266) and validation groups (n = 97). Two non-invasive models were established based on multivariable logistic regression analysis in the training group. Model 2 with a lower Akaike information criterion (AIC) was selected as a better predictive model. Receiver operating characteristic (ROC) was used to evaluate the model and was then independently validated in the validation group. The formula of Model 2 was logit (Model value) = 5.67+0.08 × Age −2.44 × log10 [the quantification of serum HBsAg (qHBsAg)] −0.60 × log10 [the quantification of serum HBeAg (qHBeAg)]+0.02 × ALT+0.03 × aspartate aminotransferase (AST). The area under the ROC curve (AUC) was 0.89 for the training group and 0.86 for the validation group. Using 2 cut-off points of −2.61 and 0.25, 59% of patients could be identified with liver fibrosis and antiviral treatment decisions were made without liver biopsies, and 149 patients were recommended to undergo liver biopsy for accurate diagnosis. In this study, the non-invasive model could predict liver fibrosis and may reduce the need for liver biopsy in HBeAg-positive CHB patients with normal or slightly increased ALT.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Chronic hepatitis B (HBV) and C virus (HCV) infection causes liver cancer. This protocol is to provide the methods used to assess the relationship between statins and HCC risk in hepatitis B or C patients. Methods: We will search comprehensively the PubMed (medline), Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure, Wanfang Database from their inception to November 2017. We will include studies that evaluated and clearly defined exposure to statins, reported the HCC incidence in hepatitis B/C patients or HBV/HCV-related cirrhosis patients, provided effective comparison groups, and reported risk estimates, such as hazard ratios, relative risks, or odds ratios with corresponding 95% confidence intervals or sufficient data for their estimation. We will use Stata (version 15.0) to compute the data synthesis carefully when a meta-analysis is allowed. Results: This study will provide a high-quality synthesis of current evidence of statins on HCC risk in hepatitis B or C patients. Conclusion: The conclusion of our systematic review will provide evidence to judge whether statin is an effective intervention for hepatitis B or C patients.

Background: Minimal hepatic encephalopathy (MHE) is a subclinical state of hepatic encephalopathy with the possibility of developing into overt hepatic encephalopathy (OHE) and having adverse outcomes. However, no preventative medicine for MHE has been recommended so far. The aim is to evaluate the therapeutic effect of the JianPi HuaZhuo XingNao formula (JPHZXN) on MHE, specifically whether JPHZXN decreases OHE occurrence, through a randomized controlled trial. Method: Seventy-two patients with MHE are enrolled and allocated in a 1:1 ratio in an experimental group and a control group. JPHZXN granules and placebos are dispatched to the experimental group and control group, respectively, for 24 weeks. The primary outcome is the incidence of developing OHE. The secondary outcomes are the patients’ performances in number connection test A and the digital sign test as well as results from the health survey and chronic liver disease questionnaire. Results: This study will provide proof regarding the therapeutic effect of JPHZXN among patients with MHE. Conclusion: The outcomes could grant clinicians an alternative choice when treating potentially progressive patients with MHE.

Tubeimoside I (Tub) is a triterpenoid saponin isolated from Bolbostemma paniculatum[Maxim]Franquet. A sensitive and validated method was developed to determine Tub in rat plasma. This method combined the qualitative and quantitative advantages from liquid chromatography coupled with hybrid ion trap-time of flight mass spectrometer (HPLC-DAD-IT-TOF-MS) and a triple quadrupole-linear ion trap mass spectrometer 5500 (Qtrap 5500), owing to the narrow molecular range of Qtrap 5500 relative to the molecular weight of Tub. Initially, ion detection was achieved using negative ionization mode along with full scan on IT-TOF-MS. The detected precursor and product ions of Tub with the optimal mass parameters were determined on Qtrap 5500 by an online stepped optimization strategy and operated in negative multiple reaction monitoring mode. A simple methanol precipitation was employed with saikosaponin A as internal standard. The method was validated over the range from 20 to 2000 ng/mL with a lower limit of quantification of 20 ng/mL for Tub in plasma. The developed method was successfully applied to the pharmacokinetic study of Tub in rats following oral administration. Moreover, this method has some directive significance for the determination of other drugs whose parent ions exceeding the upper detection limit in Qtrap 5500.

Objective. This aim is to evaluate the effect of Sijunzi decoction (SJZD) treating chronic atrophic gastritis (CAG). Methods. We performed searches in seven databases. The randomized controlled trials (RCTs) comparing SJZD with standard medical care or inactive intervention for CAG were enrolled. Combined therapy of SJZD plus conventional therapies compared with conventional therapies alone was also retrieved. The primary outcome included the incidence of gastric cancer and the improvement of atrophy, intestinal metaplasia, and dysplasia based on the gastroscopy and pathology. The secondary outcomes were Helicobacter pylori clearance rate, quality of life, and adverse event/adverse drug reaction. Results. Six RCTs met the inclusion criteria. The research quality was low in the trials. For the overall effect rate, pooled analysis from 4 trials showed that modified SJZD plus conventional medications exhibited a significant improvement (OR = 4.86; 95% CI: 2.80 to 8.44; P < 0.00001) and without significant heterogeneity compared with the conventional medications alone. None reported the adverse effect. Conclusions. Modified SJZD combined with conventional western medicines appears to have benefits for CAG. Due to the limited number and methodological flaw, the beneficial and harmful effects of SJZD for CAG could not be identified. More high-quality clinical trials are needed to confirm the results.

ChiCTR-TRC-11001263 study was the first large-scale double-blind randomized placebo-controlled traditional Chinese medicines (TCMs) and adefovir (ADV) antihepatitis B virus (HBV) infection trial in the world. A total of 560 hepatitis B e antigen- (HBeAg-) positive Chinese patients with chronical HBV were randomly classified, in 1 : 1 ratio, into two groups: experimental group (EXG) receiving TCMs + ADV and controlled group (CTG) receiving ADV + TCM-placebo treatment for 48 weeks. This paper introduces two models to model and simulate the evolutions of dynamics for the complete-response patients and the poor-response patients in EXG and CTG, respectively. The stimulated mean HBV DNA and alanine aminotransferase (ALT) levels were close to the patients’ experimental data. Analysis and simulations suggest that the activated patients’ immune functions by TCMs + ADV may not only clear infected hepatocytes, but also clear HBV, which made the complete-response patients’ mean serum HBV DNA levels in EXG reduce rapidly 12 weeks’ earlier than the ones in CTG. One can assume that both the TCMs and ADV have the function of preventing complete-response patients’ infected hepatocytes from being injured by cytotoxic T lymphocytes (CTLs); the patients’ activated immune cells may also block HBV replications.

Objective To observe the clinical efficacy and safety of Shuanghu Qinggan Granule (双虎清肝颗 粒, SQG) plus Yigan Yiqi Jieyu Granule (乙肝益气解郁颗粒, YYJG) combined with lamivudine (LAM) on chronic hepatitis B (CHB) patients.

The basic models of within-host viral infection, proposed by Nowak and May2 and Perelson and Nelson,5 have been widely used in the studies of HBV and HIV infections. The basic reproduction numbers of the two models are proportional to the number of total cells of the host's organ prior to the infection. In this paper, we formulate an amended Perelson and Nelson's model with standard incidence. The basic reproduction number of the amended model is independent of total cells of the host's organ. If the basic reproduction number R0 < 1, then the infection-free equilibrium is globally asymptotically stable and the virus is cleared; if R0 > 1, then the virus persists in the host, and solutions approach either an endemic equilibrium or a periodic orbit. Numerical simulations of this model agree well with the clinical HBV infection data. This can provide a possible interpretation for the viral oscillation behaviors, which were observed in chronic HBV infection patients.

Background. In recent years, with the popularity of CHM, its hepatotoxicity has also been increasingly noticed. However, there are still veils on causative herbs and clinical characteristics.Aim. To systematically review data on CHM induced liver injury with particular focus on causative herbs and clinical characteristics.Methods. Using terms related to CHM and liver injury, PubMed and three Chinese electronic databases were searched, which was limited to the past 5 years. Publications meeting our eligibility criteria were included and further analyzed.Results. In total, 4 single herbs, 21 patent drugs, and 4 decoctions were reported to be of hepatotoxicity, with He-Shou-Wu being the most common one (65/114). Dang-Gui and other 5 herbs were the most common ingredients of patent drugs and decoctions. All patients were assessed using the RUCAM scale, with 26 being highly probable and 28 being probable. For these 54 cases, the latent period was 30 (47) days, and 81.48% were labeled as hepatocellular injuries. Most patients (96.3%) recovered, apart from the fact that one died and one is receiving liver transplantation.Conclusions. CHM should be used carefully for hepatotoxicity. Liver injury from CHM is similar to that from conventional medicines in clinical characteristics. Details about causative herbs should be illustrated, and more RUCAM should be used in future.

Based on our previous researches, this paper introduces a new differential equation model to describe the dynamics of traditional Chinese medicines (TCM) + nucleoside analogues (NA) anti-HBV infection treatment for the chronic hepatitis B (CHB) patients. This model has five state variables. A treatment-activated specific term in this model is in charge of directly clearing patients’ HBV rather than damaging patients’ hepatocytes. As an application, we use this model to simulate the dynamics of TCM + NA anti-HBV infection personalized combination treatments. The numerical simulations and analysis show that the TCM + NA combination treatments are able to activate patients’ abilities of cytokine-midiated noncytolytic HBV clearance.

Effective treatment of chronic Hepatitis B virus (HBV) patients aims to prevent progression of chronic hepatitis B to cirrhosis, hepatocellular carcinoma, and eventually death. The use of mathematical modelling to explain the anti-HBV infection therapy has made a significant contribution for understanding the dynamics of host cells, viruses, the immune system. Chinese herbs are playing important roles for anti-HBV infec- tion treatment. Recently a new type of Chinese herbs (NTCH) has been proved to be effective for anti-HBV infection therapy. Based on a patient's anti-hepatitis B virus (HBV) infection therapy clinical data with the NTCH and our previous modified basic virus infection model (1), a new differential equation model with an immune variable is set up. The numerical simulations of the model show that the evolution of the HBV DNA of the model is agreement with in the patient's clinic plasma HBV DNA levels. The model predicts that it needs to prolong the treatment time to 4.3 years to eliminate NTCH the HBV virus in the patient's infected hepatocytes. Otherwise earlier cessation of the therapy will make the patient's HBV DNA levels return rapidly.

Based on a patient's anti-hepatitis B virus (HBV) infection therapy clinical data of a new type of Chinese herbs (NTCH, consisting of 13 ingredients) plus adefovir dipivoxil, and our previous modified basic virus infection model [1], a new differential equation model with an immune variable is set up, and aims to describe and understand the dynamics of host cells, viruses, the immune system, as well as predict the long term curative effects. The results of numerical simulations of the model indicate that the dynamics of the model is agreement with in the patient's plasma HBV DNA levels. The model predicts that it need to eliminate all HBV virus in infected hepatocytes. Otherwise earlier cessation of the therapy will make the patients' plasma HBV DNA levels return.