Traditional Chinese Medicine Granules Research Articles

Research on comprehensive quality consistency evaluation strategy for TCM granules: A case study with sugar-free Yangwei Granules produced by fluid-bed granulation

ObjectiveTo develop a quality consistency evaluation strategy for traditional Chinese medicine (TCM) granules using sugar free Yangwei Granules as a model drug, and demonstrate the effectiveness of the developed method. MethodsThe strategy integrates several methods including, HPLC fingerprint and physical fingerprint methods analyze the similarity in chemical and physical properties of the TCM granule samples. Near-infrared (NIR) spectroscopy with principal components cluster analysis method is used to monitor normal operating conditions (NOC) samples accurately and to identify different types of abnormal operating conditions (AOC) samples, particularly those that deviate from the normal range. ResultsThe combined use of HPLC fingerprint and physical fingerprint provides insights into the chemical and physical properties of the samples. NIR spectroscopy, combined with principal components cluster analysis, achieves high accuracy in monitoring NOC samples and identifying AOC samples without misjudgment. The approach proves useful as a complementary method in cases where HPLC fingerprint and physical fingerprint alone lack sufficient resolution. ConclusionThis study establishes the feasibility and utility of the integrated approach for assessing the quality consistency of TCM granules. The strategy shows a high degree of generalization and holds significant importance for enhancing the quality control processes of TCM granules.

Effects of co-application of tiotropium bromide and traditional Chinese medicine on patients with stable chronic obstructive pulmonary disease: a muilticenter, randomized, controlled trial study.

Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable disease. Traditional Chinese Medicine (TCM) has shown promising potential in COPD treatment. and we conducted a multi-center RCT to evaluate the effectiveness of TCM-based therapy in stable COPD patients. In this multicenter, double-blind RCT, a total of 200 patients were supposed to be assigned to either trial or control group randomly. Both groups received Tiotropium (18 μg) from month 0 to month 12. Trial group received additional TCM granules, while control group received a placebo from month 0 to month 6. Symptom assessment, total effective rate, lung function measurements, hospitalization rates, and quality of life were evaluated at month 0, month 6, and month 12. Adverse events were assessed at month 12. Of the initial 105 patients (aged 40-80) who completed the study, 51 were in trial group and 54 were in control group. At month 6, significant differences were observed between two groups in total effective rate (p = 0.020), sputum score (p = 0.047), changes in FVC% (p = 0.047) and FEV1 (p = 0.046). At month 12, significant differences were observed in sputum score (p = 0.020), FVC (p = 0.042), and change in FEV1 (p = 0.013). Compared to baseline, they both demonstrated improvements in symptoms, acute exacerbation, lung function, quality of life, and exercise tolerance. TCM treatment effectively improved total effective rate, sputum symptom, FVC%, FEV1, and exhibited prolonged efficacy in improving sputum symptoms and FEV1 in stable COPD patients.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=6029 identifier ChiCTR-TRC-13003531.

Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅰ): classification of processing routes

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Induction of Nrf2-EpRE-mediated gene expression by hydroxyanthraquinones present in extracts from traditional Chinese medicine and herbs.

Hydroxyanthraquinones that can be present in traditional Chinese medicine (TCM) and herbal extracts have claimed beneficial intestinal effects. We examined the ability of a panel hydroxyanthraquinones, and methanolic extracts from selected TCM and herbal granules to activate Nrf2-EpRE mediated gene expression using a reporter-gene assay. The results indicate that purpurin, aloe-emodin, 2-hydroxy-3-methylanthraquinone and rhein induced Nrf2 mediated gene expressions with a high induction factor (IFs>10), with BMCL10 values (the lower confidence limit of the concentration giving 10% added response above background) of 16 μM, 1.1 μM, 23 μM and 2.3 μM, respectively, while aurantio-obtusin, obtusifolin, rubiadin 1-methyl ether and emodin were less potent (IFs<5), with BMCL10 values for added response above background level of 4.6 μM, 15 μM, 9.8 μM and 3.8 μM, respectively. All TCM extracts and the herbal extracts of Aloe Vera, Polygonum multiflorum, Rubia (cordifolia) and Rheum officinale activated the Nrf2-EpRE pathway. Of the TCM extracts, Chuan-Xin-Lian-Kang-Yan-Pian was the most potent Nrf2-inducer. LC-MS/MS analysis indicated the presence of selected hydroxyanthraquinones in the extracts and herbs, in part explaining their Nrf2-EpRE mediated activity. In conclusion, different hydroxyanthraquinones have different potencies of Nrf2 activation. The Nrf2 activation by extracts from TCM and herbs can be partially explained by the presence of selected hydroxyanthraquinones.

Role of Alternative Medical Systems in Adult Chronic Kidney Disease Patients: A Systematic Review of Literature.

There is a growing interest in the use of alternative medical systems (AMS), such as traditional Chinese medicine (TCM), ayurveda, homeopathy, and naturopathy, among chronic kidney disease patients. This review summarizes the efficacy and safety of AMS interventions in chronic kidney disease (CKD) patients. A systematic review was conducted in MEDLINE, Embase, Scopus, CINAHL, CENTRAL, and PsycINFO in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Synthesis without meta-analysis (SWiM) guidelines. Randomized controlled trials (RCTs) which evaluated the use of AMS among adult CKD patients were included. The efficacy of each AMS was assessed based on improvement in biochemical markers or reduction in symptom severity scores. All adverse reactions were recorded. Of the 14,583 articles retrieved, 33 RCTs were included. TCM (n=20) and ayurveda (n=6) were the most well-studied. Majority of studies (66.7%) had a sample size <100. Common indications evaluated included improvement in renal function (n=12), proteinuria (n=5), and uremic pruritus (n=5). Among TCM, acupuncture and syndromes-based TCM granules formulation were shown to improve estimated glomerular filtration rate (eGFR) by 5.1-15.5% and 7.07-8.12% respectively. Acupuncture reduced uremic pruritus symptoms by 54.7-60.2% while Huangkui, Shenqi granules, and Tripterygium wilfordii Hook F reduced proteinuria by 18.6-50.7%, 61.8%, and 32.1% respectively. For Ayurveda, camel milk and Nigella sativa oil improved eGFR by 16.9% and 86.8%, respectively, while capsaicin reduced pruritus scores by 84.3%. Homeopathic verum medication reduced pruritus scores by 29.2-41.5%. Nausea was the most common adverse effect reported with alpha-keto amino acids (0.07%), Nigella sativa oil (7.04%), and silymarin (10%). TCM and ayurveda were more well-studied AMS therapies that demonstrated efficacy in CKD patients. RCTs with larger sample sizes are needed to ascertain the efficacy and safety of promising AMS.

Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial

BackgroundNon-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone.MethodThis multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD–HRQL, and TCM syndromes scales.DiscussionPrevious research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients’ physical and psychological burdens, and achieve good social benefits.Trial registrationClinicaltrials.gov NCT04340297. Registered on April 9, 2020

Traditional Chinese medicine for promoting mental health of patients with COVID-19: a scoping review.

A scoping review was conducted by searching PubMed, Web of Science, CNKI, Wanfang database, VIP database, and SinoMed, with the retrieval time being from the establishment of the database to April 18, 2022. The basic information of the included studies, objective, design, types of patients, interventions, outcomes, etc., was reviewed and summarized narratively. Methodological quality was assessed using the Cochrane Risk of Bias assessment tool, the methodological index for non-randomized studies or the Newcastle-Ottawa scale. We identified 30 traditional Chinese medicine (TCM) studies from six databases. Among them, finished randomized controlled trials (n = 16) accounted for most of the studies, followed by single-arm studies (n = 9). In terms of study theme, 20 studies defined the mental health of patients with COVID-19 as the research theme. Psychological assessment was included in the inclusion criteria (performed before participation) of nine studies, whereas the other studies only mentioned the mental outcomes. TCM interventions included TCM exercises (Yijinjing, Baduanjin, Liuzijue, Taichi), acupoint stimulation (auricular and body points), moxibustion, decoction, or granules based on TCM syndrome differentiation, decoction, or granules with fixed formulae (Baidu Jieduan granules, Xuanfei Baidu decoction, and Qingfei Paidu decoction), Chinese patent medicine (Jinhua Qinggan granules), TCM psychological therapy (TCM ideological therapy, TCM five-tone therapy, and TCM psychological sand table), and TCM nursing (dialectical care, dialectical diet, and psychological counseling). Anxiety and depression were the main outcomes evaluated in regard to mental health in patients with COVID-19. The limitations of methodological quality were predominantly from follow-up, blinding, and registration. Positive results were reported by 27 studies (90%, n = 30). We summarized the existing literature about the impact of TCM on mental health in patients with COVID-19. The number of studies evaluating the impact of TCM on mental health is encouraging, but overall methodological quality was low. Several TCM interventions warrant further evaluation, particularly among populations outside of China, for the purpose of establishing supporting evidence. More importantly, research with stronger methodological quality needs to be developed. http://links.lww.com/AHM/A36.

Efficacy and safety of Fuzheng Huayu tablet on persistent advanced liver fibrosis following 2 years entecavir treatment: A single arm clinical objective performance criteria trial

Ethnopharmacological relevanceAntiviral therapy can alleviate liver fibrosis in chronic hepatitis B, but it has a limited effect on advanced liver fibrosis/cirrhosis. Traditional Chinese medicine (TCM), particularly FuZheng HuaYu (FZHY) tablet, appears to have an antifibrotic effect, but its improving resolution of hepatitis b virus (HBV) -associated advanced fibrosis and experienced anti-viral treatment has not been investigated. Aim of the studyTo observe the safety and efficacy of adjunctive FZHY on the HBV-associated cirrhosis patients who received 2 years of entecavir but still with advanced fibrosis. MethodsAn open-label, multicentre, single arm trial. 251 patients were included and treated with TCM consisted of FZHY tablets 1.6 g and granules, three times a day in addition to entecavir 0.5 mg daily for an additional 48 weeks. Primary outcome was regression of fibrosis (the proportion of patients with a 1-point decrease in the Ishak liver fibrosis score from baseline to week 48). ResultsFibrosis regression occurred in 94 of 184 patients with paired liver biopsy (51.09%, 95% CI: 43.9～58.0). In 132 compensated cirrhosis patients (Ishak score ≥5), 56.06% (74/132, 95% CI: 47.5～64.2) showed fibrosis regression and reached the goal of 54% (15% more than entecavir mono-therapy). 10 patients occurred adverse reaction, most of them were mild, and all recovered or achieved remission. ConclusionsThe combination therapy of FZHY, TCM granules and ETV could regress the liver fibrosis in the patients with HBV cirrhosis, who experienced 2 years of ETV treatment, and it is safe and well tolerated.

COVID-19 Knowledge/Practices, Mental Status, and Return-To-Work Concerns Among Healthcare Workers in Huangzhou District, Huanggang City, China.

Objective:This study investigated the COVID-19-prevention knowledge and practices of healthcare workers (HCWs), their psychological states concerning the return to work, and their trust and requirements in using traditional Chinese medicine (TCM) to prevent and treat COVID-19. It is hoped that the study can serve as a reference for policy making during the resumption of work in other countries or regions experiencing similar situations.Methods:This study comprised a quantitative cross-sectional online survey design. Purposive sampling and Cluster sampling were used to recruit all HCWs working in public hospitals in Huangzhou District, Huanggang City, Hubei Province, China. From April 23 to May 14, 2020, surveys were sent electronically to all 13 public hospitals in this area.Results:In total, 2,079 responses were received and 2,050 completed forms were included. After analysis, 47.9 and 46.6% of HCWs indicated that they possessed very good knowledge or good knowledge of preventative measures, respectively. Multivariable log-binomial regression indicated that male, tertiary hospital, medical staff, and undergraduate/postgraduate qualification were associated with good knowledge. Good knowledge was also well-correlated with good practice (OR: 3.277; 95% CI: 2.734–3.928; P < 0.01). 59.8% of HCWs reported worries about resuming work; especially asymptomatic infections. The Self-Rating Anxiety Scale (SAS) indicated that 10.8% of participants had mild anxiety, 1.5% moderate anxiety, and 0.1% severe anxiety. Female, divorced/widowed, and working in a high risk hospital (the Huangzhou District People's Hospital was used for throat swab examinations of returning workers) were risk factors for concerns about resuming work and anxiety symptoms. However, good preventive knowledge was a protective factor for anxiety. HCWs' trust in using TCM to treat COVID-19 was significantly higher than their trust in using TCM for prevention (P < 0.001). Regarding preferences for preventative TCM products, oral TCM granules were the most preferred (62.4%). HCWs also indicated they wanted to know more about the clinical efficacy, applicable population, and adverse reactions of preventative TCM products (89.3, 81.1, and 81.4%, respectively).Conclusion:While HCWs had good knowledge of COVID-19 preventative measures, this did not eliminate the psychological impact of resumption of work. Promotion of COVID-19 prevention knowledge reduces the risk of infection, and alleviates the worries and anxiety symptoms of HCWs about resuming work (especially in administrative staff, those with low education, and those working in primary hospitals). Additional psychological support is required for female HCWs, divorced/widowed HCWs, and those working in high-risk hospitals. Finally, systematic trials of preventative TCM products are recommended.

Characteristics and development assumptions of personalized traditional Chinese medicine granules

Personalized traditional Chinese medicine(TCM) granules are positioned as a solid dosage form of TCM decoctions, boasting strong applicability and wide application range. The market prospect of personalized TCM granules is promising in that their preparation by mixed decoction makes up for the shortcoming of formula granules like the Chinese patent medicine granules and classical TCM prescription granules whose components cannot be changed flexibly. However, such factors as insufficient basic research, equipment mismatch, and low process commonality have limited their clinical application. After analyzing the characteristics of perso-nalized TCM granules, their production status, and the bottlenecks restricting their development, this paper pointed out the meaning and key points of developing a generalized preparation process for personalized TCM granules and affirmed the vital roles of the preparation and process prediction system and the on-line detection technology in improving the productivity of granulation. Finally, some assumptions on technology development for solving the specific problems of personalized TCM granules were shared to provide some ideas for the application and development of personalized TCM granules in clinical practice.

Effects of traditional Chinese medicine combined with chemotherapy for extensive-stage small-cell lung cancer patients on improving oncologic survival: study protocol of a multicenter, randomized, single-blind, placebo-controlled trial

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) is characterized by extensive metastases, aggressive progression, and poor prognosis. Chemotherapy is applied as a preferred first-line regimen for ES-SCLC, but inadequate for improving its overall survival. Traditional Chinese medicine (TCM) is widely used in the clinical practice of ES-SCLC for its synergy with chemotherapy. However, there is still no substantial evidence to prove that TCM can effectively improve the long-term efficacy of ES-SCLC patients. The study intends to determine whether the TCM with chemotherapy can improve the overall survival (OS) in treating with ES-SCLC when compared with chemotherapy alone.Method/designA multicenter, randomized, single-blind, placebo-controlled clinical trial will be conducted to determine whether the TCM granules combined with chemotherapy can improve the OS of ES-SCLC. Two hundred seventy participants will randomly receive 4–6 cycles (21 days per cycle) of chemotherapy plus TCM granules or placebo. The primary outcome measure is OS. The secondary outcome measures includes progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and tumor markers. Visits will be performed at the end of each cycle during the treatment period and then every 3 months in the follow-up period until the patients’ death or study completion.DiscussionThe study’s result will provide a high-level evidence for TCM granules using with chemotherapy on the first-line treatment of ES-SCLC.Trial registrationChinese Clinical Trial Registry ChiCTR1900022991. Registered on 6 May 2019 (prospective registration).

Exploratory study on preparation of high drug loading granules with traditional Chinese medicine raw powder as carriers

With Sangtang Yin granule as model drug,and based on the strategy of &quot; unification of medicines and excipients&quot;,the feasibility of preparing high drug loading granules with traditional Chinese medicine( TCM) raw powder as carrier was explored. The powder yield,particle size and particle size distribution,fillibility,flowability,hygroscopicity,reconstituability and other key physical properties relating to preparations of 8 herbs( Dioscoreae Rhizoma,Euryales Semen,Atractylodis Macrocephalae Rhizoma,Coicis semen,Poria,Puerariae Lobatae Radix,Puerariae Thomsonii Radix and Coicis Semen by stir-frying with bran) were studied after being smashed,and the feasibility of taking them as excipients of TCM granules was evaluated by co-spray drying,dry granulation and other preparation techniques. According to the results of the physical properties of raw powders,raw powders of Dioscoreae Rhizoma,Euryales Semen and Puerariae Thomsonii Radix had a high powder yield,uniform particle size distribution,good fillibility,poor hygroscopicity and good reconstitutability,with the feature of assisting granule forming. Compared with the prescription of spray dry powder Sangtang Yin without any excipient,the co-sprayed powder had a high yield,good fillibility and compressibility. The yield of dry granules prepared by co-spraying dry powder was increased by more than 10%,and the particles had a uniform color,good fluidity and dissolubility with the drug-loading rate up to 100%. Based on the physical characteristics of TCM raw powder combined with the analysis of the preparation process,Dioscoreae Rhizoma and Puerariae Thomsonii Radix raw powder were selected as the carriers of granule preparations,and Sangtang Yin granule without any excipient was successfully prepared. The findings provide a feasible idea for the preparation of TCM granules with a high drug loading capacity.

Similarity Evaluation on the Compound TCM Formulation "Huoling Shengji Granule" and Its Placebo by Intelligent Sensory Evaluation Technologies and the Human Sensory Evaluation Method Based on Critical Quality Attributes.

To evaluate the similarity of Huoling Shengji granule (HLG) and its placebo at both granules and solution status, the innovative methods that consist of intelligent sensory evaluation technologies and human sensory evaluation methods were developed based on critical quality attributes (CQAs) of granule. The CQAs for traditional Chinese medicine (TCM) placebo granule were mainly divided into three categories: formulation attributes, visual attributes, and attributes of taste and smell. In this investigation, the novel intelligent sensory evaluation technologies including the physical property testing apparatus, computer vision system, color card, and electronic tongue (E-tongue) were employed for characterization of CQAs of HLG and its placebo. Meanwhile, human sensory evaluation by test panels was used to description the HLG and its placebo in terms of appearance, color, taste, and smell. On that basis, the similarity of placebo to CQAs of HLG was assessed by calculating the angle cosine values. The intelligent and human sensory evaluation results showed that the similarity values of HLG and its placebo about the CQAs at granule and solution status were all close to 1, which means that the two preparations have high similarities. In this study, the established similarity evaluation methods based on the CQAs were convenient and reliable, which can be utilized to evaluate the similarity of TCM granule and their placebo at granule and solution status, and demonstrated to be well applied in placebo-controlled trials.

Chinese herbal medicine combined with entecavir to reduce the off-therapy recurrence risk in HBeAg-positive chronic hepatitis B patients: a multi-center, double-blind, randomized controlled trial in China

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

Safety and therapeutic effects of anti-fibrotic Traditional Chinese Medicine Fuzheng Huayu on persistent advanced stage fibrosis following 2 years entecavir treatment: Study protocol for a single arm clinical objective performance criteria trial

BackgroundHepatitis B virus (HBV) infection is an important etiology for chronic hepatitis globally, and especially so in China. HBV infection can lead to the development of cirrhosis through the pathological process of liver fibrosis. The effective suppression of HBV replication with NAs or interferon-alpha can histologically regress the fibrotic pathological process, but there remain patients who have achieved anti-viral responses and normalization of serum liver tests, but not liver fibrosis regression. This subset of patients typically presents with advanced liver fibrosis at baseline. Therefore, it is reasonable to administer the anti-fibrotic agents, coupled with antivirals for patients with advanced liver fibrosis due to HBV, in order to improve the fibrotic regression of the patients. Fuzheng Huayu (FZHY) tablet is a botanical product with evidence demonstrating its efficacy against mild to moderate liver fibrosis. The current clinical trial evaluates the efficacy and safety of the combination therapy of traditional Chinese medicine (TCM) (FZHY and herbal granule) and entecavir for HBV compensated cirrhosis. We will enroll HBV patients who presented with a good viral response after 2 years of entecavir treatment but had advanced liver fibrosis (≥Ishak F5). MethodsThis is a single-arm clinical trial, conducted in 20 centers in mainland China over a period of 60 weeks, including 48 weeks of treatment observation and 12 weeks of follow-up. The main inclusion criteria include HBsAg positive more than 6 months, 2 years administration of entecavir, HBV DNA less than 20 IU/ml, liver fibrotic stage ≥ F5, and Child-Pugh scoring <7 (Stage A). The sample size is estimated to be about 190, considering a 20% drop-out and 60% of patient's compliance for the second liver biopsy so a total of 350 participants will be enrolled. All eligible participants are divided into 3 subgroups according to the TCM clinic pattern. And all patients will take 1 Entecavir tablet (0.5 mg) per day, 4 FZHY tablets (1.6 g) three times a day, and specific TCM granule three times a day, which is decided by TCM clinical patterns (CPs) differentiation. The patients were treated for 48 weeks, and follow-up visits at 12, 24, 36, 48 weeks and 60 weeks. The patients will receive the second liver biopsy at the end of 48 weeks, with a 12 weeks follow-up after that.The primary endpoint is the proportion of subjects with a 1-point improvement of liver fibrosis stage using the Ishak score from baseline to week 48 in the study, according to consensus readings evaluated by a panel of hepato-pathologists. The secondary endpoints are the brightness-mode ultrasonic, fibrotic biomarkers. The adverse events (AEs) will be recorded for 60 weeks, and the safety of the combination therapy will be evaluated. Meanwhile, the efficacy in the 3 sub-groups will be stratified and analyzed. DiscussionThe study has been designed to test the therapeutic effects and safety of the combination therapy of FZHY and herbal granule with entecavir on persistent advanced stage fibrosis/cirrhosis following 2 years entecavir treatment, and to explore an effective integrative therapy on HBV cirrhosis. Trial registrationClinicalTrials.gov. NCT02241616. Registered on September 16, 2014.

Traditional Chinese medicine in the treatment of idiopathic pulmonary fibrosis based on syndrome differentiation: Study protocol of an exploratory trial

BackgroundIdiopathic pulmonary fibrosis (IPF) has a poor prognosis and is often a kind of heavy financial burden to patients. Currently, few treatments are available for IPF. Clinical practice of traditional Chinese medicine (TCM), using a syndrome differentiation approach, offers some treatment success in IPF. However, there is no sufficient evidence-based study of the role of TCM in IPF management to make strong conclusions. This study evaluates the efficacy and safety of TCM in the treatment of IPF. Methods and designA multicenter, exploratory, randomized, double-blind and placebo-controlled trial is planned. A total of 80 patients will be enrolled in the study, which will include 26 weeks of treatment. Participants will be randomly assigned into TCM group or control group in a 1:1 ratio. The TCM group will be given TCM granules based on syndrome differentiation. Formulae include Bao-fei Hua-xian granule for lung qi deficiency, Jin-shui Huan-xian granule for lung-kidney qi deficiency and Yang-qing Kang-xian granule for yin deficiency and inner heat. The control group will be given a corresponding TCM granule placebo. The efficacy and safety of interventions will be evaluated by the outcome variables, including frequencies of acute exacerbations, pulmonary function, clinical symptoms, dyspnea, health-related quality of life (HRQoL), 6-minute walk distance and safety indicators. DiscussionIt is hypothesized that TCM will decrease the frequency of adverse events, improve pulmonary function and HRQoL, based on our clinical experience. This trial is the first study of TCM treatment in IPF that is based on syndrome differentiation and will evaluate the efficacy and safety of TCM in IPF. Trial registrationThis study was registered on www.Chictr.org.cn: ChiCTR-IIR-17013532. Register date: November 24, 2017.

RETRACTED:Effects of Yin-nourishing and blood-cooling decoction on proteinuria and Renal Tubular damage in IgA Nephropathy

Abstract Observe the effects of Yin-nourishing and blood-cooling decoction on proteinuria, Hematuria, urine PDGF-DD, urinary MBL, urinary Dendrin, urinary AGT, glomerular and Renal Tubular damage in IgA Nephropathy to explore its treatment effects on IgAN proteinuria, hematuria, Urine PDGF-DDD, Urine MBL, Urine Dendrin and Urine AGT as well as its protective effect on kidney. Methods: Thirty SD (Sprague Dawley) rats aged 6 to 8 weeks were divided into blank group, model group, traditional Chinese medicine group, western medicine group and combination group. Model group and three treatment groups using bovine serum albumin+ lipopolysaccharide+ carbon tetrachloride to model 1IgAN.one week after the completion of the model, The normal group and the model group were intragastric with saline once a day. The Chinese medicine group was fed with aqueous solution of traditional Chinese medicine granules once a day (4 ml each time, containing 9.2 gs of raw medicine). The western medicine group was given benapril solution once a day and the dosage is 15 times that of an adult with weight of 60kg. The combination of Chinese and western medicine was treated with the above half dose of water solution of Yin-nourishing and blood-cooling decoction and benazepril solution. After four weeks of intragastric administration according to the above scheme, urine and venous blood of rats were collected and their erythrocytes, 24-hour urinary protein quantification, urine PDGF-DD, urine MBL, Dendrin, urine AGT and blood biochemical indexes were detected. Direct immunofluorescence is adopted to detect its glomerular IgA deposition intensity and observe Changes of glomerulus and tubule through HE staining and PAS staining. Results:1. Compared with the model group, the urine erythrocyte, proteinuria, urinary MBL and urine Dendrin in the traditional Chinese medicine group decreased significantly and the difference was statistically significant (P

Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injuryIssued by China Food and Drug Administration

Drug-induced liver injury (DILI), defined as liver injury caused by a drug and/or its metabolites, is a common clinical adverse drug reaction1, 2, 3, 4. This type of injury can cause acute liver failure and even death in severe cases5. DILI accounts for many drug warnings and is an important cause of failure in the clinical development of new drugs and new forms of traditional Chinese medicine (TCM). Thus, liver injury from drugs has attracted close attention from medical professionals, the pharmaceutical industry, and the general public6, 7, 8. For thousands of years, TCM has contributed to the prevention and treatment of disease, to the development of the Chinese nation, and to the quality of life of Chinese people. For many individuals, TCM remains an essential component of modern life. However, continuous improvements in monitoring adverse drug reactions/events (ADRs/ADEs), along with increased TCM use worldwide has frequently identified TCM-associated safety issues such as DILI9, 10. This situation imposes serious obstacles to the research and development of new, safe TCM drugs and the viability of TCM industries. Due to the lack of specific diagnostic indicators, an exclusion diagnosis of DILI has been commonly adopted, but this approach has shown a high rate of misdiagnosis. TCM DILI is often overlooked because of the pharmaceutical complexity of TCM, the limited basic information on the quantities of TCM components, as well as the increasingly common use of drug combinations. The causal relationship between liver injury and TCM is also difficult to clarify. In addition, potential TCM toxicity is often overlooked by the public since TCM preparations are commonly regarded as “natural, without toxic and side effects”. For these reasons and because developers and enterprises have paid insufficient attention to ADRs, the prevention and control of TCM safety risks is extremely difficult11. Therefore, the establishment of an objective and scientific technical system for assessing and identifying TCM DILI is needed. To this end, with strengthening the risk management of the entire drug life cycle as the main goal, the China Food and Drug Administration (CFDA)of China organized experts in related fields to develop the Guidance for Clinical Evaluation of Traditional Chinese Medicine-Induced Liver Injury. This task was accomplished by integrating the consensus of Chinese and international experts with research progress in the fields of medicine and pharmacy as well as in clinical and scientific research. This document aims to provide advice and assistance to relevant institutions and personnel in identifying the risk signals of TCM DILI; scientifically assess the causal relationship between patients׳ liver injury and TCM; effectively reduce misdiagnosis; fully evaluate the safety, risks and benefits of relevant TCM; and purposefully develop prevention and control measures for TCM DILI. These activities are needed to reduce the failure rate of new TCM drug research and development (R&D) and the risk of clinical use as well as to promote a viable TCM industry in China. This guide is designed for the evaluation of DILI and for risk control throughout the entire life cycle of TCM products, including the research and development stages of new drugs and post-marketing stage. It should also be used for TCM R&D, as well as by medical and regulatory agencies. Each drug marketing authority must carry the main responsibility for the product and not only strengthen the management of the entire lifecycle of the product but also take realistic and effective risk control measures to ensure the safety of public drug use. The TCMs (including ethnomedicines) in this guide consist of the TCM preparations that are being studied and those already on the market. This guide can be used as a reference for clinically used TCM decoctions and tablets, formulated TCM granules, TCM extract, homemade herbal medicines, TCM-containing health products and TCM health foods as well as relevant excipients. Many problems that urgently require in-depth study and solutions still exist in the field of TCM DILI. This guidance will be continuously revised and improved in accordance with research progress on TCM DILI and regulatory requirements.

Antioxidation and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy.

BackgroundTang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN).MethodsDPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS.ResultsThe administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α.ConclusionThe results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.