Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method / 中国中药杂志

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study / 中西医结合学报

OBJECTIVE@#Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC), and Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) Granule, a compound of traditional Chinese herbal medicine, side-by-side with sorafenib for the treatment of advance HCC.@*METHODS@#Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process.@*RESULTS@#Of the 325 patients included, 161 received JD Granule and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83-9.47) in the group receiving JD Granule and 8 months (95% CI: 6.67-9.80) in the group receiving sorafenib, with half-, 1- and 2-year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD Granule group (9.03 months; 95% CI: 6.37-14.2) and the sorafenib group (7.93 months; 95% CI: 6.5-9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD Granule group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.@*CONCLUSION@#Compared to sorafenib, JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine / 中西医结合学报

Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.

The application status of Chinese herbal medicine in military health service in China / 中国结合医学杂志

Military medicine has had a long history in China since the emergence of the war. Chinese medicine, especially Chinese herbs, was widely used in China as well as other Asian countries for the prevention and treatment of diseases in the military for hundreds of years. However, the use of Chinese medicine in military health service has never been well studied. In this article, we briefly summarize the application status of Chinese herbal medicine in military health service in China, putting particular emphasis on special military environment, in an attempt to build a bridge between Chinese medicine and military health service and promote the quality of health service for the military and maintain world peace.

Prevalence of neutralizing antibodies against liver-tropic adeno-associated virus serotype vectors in 100 healthy Chinese and its potential relation to body constitutions / 中西医结合学报

Recombinant adeno-associated virus (rAAV) serotype 2, 3 and 8 vectors are the most promising liver-tropic AAV serotype vectors. Liver diseases are significant problems in China. However, to date, few studies on AAV neutralizing antibodies (Nabs) were working with the Chinese population or with the rAAV3 vectors. The present study aimed to determine the prevalence of Nabs in Chinese population against wild-type AAV2, AAV3 and AAV8 capsids as well as additional two AAV3 variants. In addition, we performed a preliminary analysis to investigate the potential influence of traditional Chinese medicine body constitutions on AAV Nabs. Our work demonstrated that the majority of healthy Chinese subjects were positive for AAV Nabs, with the order of AAV2>AAV3=AAVLK03>AAV8. There was no difference between: 1) AAV3 and its variants; 2) male and female subjects; and 3) different age cohorts (≤35, 36-50, and ≥51 years old). People in the Qi-deficiency constitution had significantly increased AAV8 Nabs than people in the Gentleness constitution. Our studies may have impact on the future clinical design of AAV-based gene therapy in the Chinese population.

Quality assessment of clinical research on liver cancer treated by intra-arterial infusion of Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the methodological quality of clinical research on Chinese medicine (CM) applied by intra-arterial infusion in treating primary liver cancer (PLC).</p><p><b>METHODS</b>Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and three Chinese databases, including Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI) and China Academic Journal (VIP) were searched. Chinese articles were also searched manually in 16 journals. Two reviewers independently selected studies, the quality of literatures were assessed according to the Cochrane Collaboration method of quality assessment.</p><p><b>RESULTS</b>A total of 14 articles met the inclusion criteria for this review. Only three of these articles described the randomization method used. None of the studies was blinded. All of the articles didn't report the calculation of the sample size. Only six studies mentioned adverse reactions. All of the studies were of grade C according to the Cochrane Collaboration method. Six studies reported results of survival, and only two of these reported better efficacy in the treatment groups.</p><p><b>CONCLUSIONS</b>The quality of studies concerned intra-arterial infusion of CM in treating with PLC was poor and the exact effect of these medicines still need evaluation. Well designed RCTs with large sample sizes, adequate follow-up data and reliable methods of assessment are needed to better appraise the real effect of CMs in the treatment of PLC patients.</p>

Interpretation of illness in patients with chronic diseases from Shanghai and their associations with life satisfaction, escape from illness, and ability to reflect the implications of illness / 中西医结合学报

<p><b>OBJECTIVE</b>The aim of this study is to analyze how patients with chronic diseases from Shanghai interpret their disease, and how these interpretations influence patients' life satisfaction, intention to escape from their illness and their ability to reflect on the implications of their illness.</p><p><b>METHODS</b>A cross-sectional study enrolling 142 patients (mean age (50 ± 16) years; 63% men, 37% women) with chronic diseases (60% cancer) was recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China and surveyed using standardized questionnaires.</p><p><b>RESULTS</b>Patients with chronic diseases from Shanghai interpreted their illness mostly as an Adverse Interruption of Life (55%), as a Threat/Enemy (50%), but also as a Challenge (49%), and only rarely as a Call for Help (18%) or as a Punishment (13%). Particularly fatalistic negative (i.e., Threat/Enemy, Adverse Interruption of Life) and strategy-associated disease interpretations (i.e., Relieving Break, Call for Help) were moderately associated with patients' intention to escape from illness. In contrast, positive interpretations (i.e., something of Value, Challenge) and also the guilt-associated negative interpretation Failure were moderately related with patients' ability to reflect on their illness. However, life satisfaction was weakly associated only with the view that illness might be a Challenge. Interestingly, 58% of those who would see their illness as an Adverse Interruption (AI+) could see it also as a Challenge (Ch+). Detailed analyses showed that AI+Ch+ patients differ from their AI+Ch- counterparts significantly with respect to their ability to reflect life and implications of illness (F=9.1; P=0.004).</p><p><b>CONCLUSION</b>The observed interpretations of illness, particularly the negative perceptions, could be used as indicators that patients require further psychological assistance to cope with their burden. Helping AI+ patients see their illness also as a Challenge, and thus develop a higher Reflection on Life Concerns, would be greatly beneficial, and encourages further research.</p>

Psychosocial and spiritual needs of patients with chronic diseases: validation of the Chinese version of the Spiritual Needs Questionnaire / 中西医结合学报

<p><b>OBJECTIVE</b>Even in secular societies, a small portion of patients find their spirituality to help cope with illness. But for the majority of patients, psychosocial and spiritual needs are neither addressed nor even considered a relevant factor by health care professionals. To measure such specific needs, the Spiritual Needs Questionnaire (SpNQ) was developed. The aim of this study was to validate the Chinese version of the SpNQ (SpNQ-Ch) and thus to measure psychosocial and spiritual needs of Chinese patients.</p><p><b>METHODS</b>This was a cross-sectional study among 168 patients with chronic diseases who were recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China using standardized questionnaires. We performed reliability and factor analyses, as well as analyses of variance, first order correlations and regression analyses.</p><p><b>RESULTS</b>The 17-item SpNQ-Ch had a similar factorial structure as the original version with two main and three minor factors which accounted for 64% of variance, and internal consistency estimates (Cronbach's α) ranging from 0.51 to 0.81. Included were the 4-item scale Inner Peace Needs, the 5-item scale Giving/Generativity Needs, the 5-item scale Religious Needs (with 2 sub-constructs, Praying and Sources), and a 3-item scale Reflection/Release Needs. In Chinese patients with cancer (63%), pain affections (10%), or other chronic conditions (23%), the needs for Giving/Generativity (which refer to categories of Connectedness and Meaning) and Inner Peace Needs scored highest, while Religious Needs and the Reflection/Release Needs scored lower.</p><p><b>CONCLUSION</b>The SpNQ-Ch is congruent with its primary version, and can be used in future studies with the mostly nonreligious patients from China. First findings indicate specific psychosocial and spiritual needs which should be addressed by health care professionals to support patients in their struggle with chronic illness in terms of psycho-emotional stabilization, finding hope and meaning, and thus achieving peaceful states of mind despite chronic illness.</p>

Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial / 中西医结合学报

<p><b>BACKGROUND</b>Disease recurrence is a main challenge in treatment of hepatocellular carcinoma (HCC). There is no generally accepted method for preventing recurrence of HCC after resection.</p><p><b>OBJECTIVE</b>To compare the efficacy of a traditional herbal medicine (THM) regimen and transarterial chemoembolization (TACE) in preventing recurrence in post-resection patients with small HCC.</p><p><b>DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS</b>This is a multicenter, open-label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE.</p><p><b>MAIN OUTCOME MEASURES</b>Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure.</p><p><b>RESULTS</b>Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 (P = 0.048). Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively (P = 0.026). Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar.</p><p><b>CONCLUSION</b>In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.</p>

Preventive effects of jiedu granules combined with cinobufacini injection versus transcatheter arterial chemoembolization in post-surgical patients with hepatocellular carcinoma: a case-control trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of Jiedu granules, a Chinese medicine (CM) compound, plus cinobufacini injection, which was extracted from skin of Bufo bufo gargarizans Cantor, to prevent the recurrence of hepatocellular carcinoma (HCC) after surgical resection.</p><p><b>METHODS</b>In this case-control trial, a total of 120 patients who stayed in Changhai Hospital were enrolled from December 2001 to December 2006. Sixty patients were treated with Jiedu granules plus cinobufacini injection to prevent tumor recurrence after operation (CM group) and 60 patients were treated with transcatheter arterial chemoembolization (TACE) after operation (TACE group). Progression-free survival (PFS) and overall survival (OS) rates were determined to evaluate the therapeutic effects of post-operative management of patients with HCC.</p><p><b>RESULTS</b>PFS in the CM group was 18.07 months [95% confidence interval (CI): 12.49-23.65] and the 1-, 2-, 3-, 4- and 5-year PFS rates were 61%, 39%, 26%, 22% and 12%, respectively. PFS in the TACE group was 8.03 months (95% CI: 6.63-9.44) and the 1-, 2-, 3-, 4- and 5-year PFS rates were 34%, 11%, 7%, 2% and 0%, respectively. There was significant difference in survival rate between the two groups (P<0.01). The mean survival time (MST) of patients in the CM group was 49.53 months versus 39.90 months of the TACE group. The 1-, 2-, 3-, 4- and 5-year survival rates were 90%, 82%, 80%, 70% and 63%, respectively, in the CM group, and 79%, 70%, 60%, 60% and 36%, respectively, in the TACE group. There was significant difference in survival time between the two groups (P=0.045).</p><p><b>CONCLUSIONS</b>Jiedu granules plus cinobufacini injection, a combination that is commonly used for post-operation management of HCC, can postpone tumor recurrence and metastasis, prolong the survival time and increase the survival rate of post-surgical patients with HCC. However, these findings need to be confirmed in a prospective, randomized controlled trial.</p>

Diagnosis and treatment of malignant tumors using integrated traditional and western medicine: progress, challenges and reflections / 中国结合医学杂志

Malignant tumors are one of the leading causes of death in the world. Considerable progresses have been made on the treatment of tumors in recent decades, especially in the prevention, early diagnosis and the model changing of therapeutics. But we are still facing tough challenges, including the increasing treatment burden and limited improvement of efficacy. In China, Chinese medicine (CM) provides a powerful arsenal to fight against tumors. CM can be well applied to the onset and progression of tumors in China, bearing the characteristics of multi-target, multi-phase and multi-effect. But there are also many problems demanding urgent attention in the use of CM. Some most debated problems in this field were summarized. We should upgrade our concepts in using CM, find its position scientifically, and establish evidence of its effect by high quality clinical research.

Effect of cinobufacini injection on the tumor growth of tumor bearing rats of different constitutions / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe effects of cold- and hot-property herbs and effects of hot and cold constitutions on the tumor growth of tumor bearing rats, and to observe the effect of Cinobufacini Injection (CI) on the tumor growth of tumor bearing rats of different constitutions.</p><p><b>METHODS</b>Eighty healthy male Wistar rats were randomly divided into eight groups, i.e., the tumor bearing control group, the tumor bearing heat syndrome group, the tumor bearing cold syndrome group, the heat syndrome tumor bearing group, the cold syndrome tumor bearing group, the tumor bearing CI group, the heat syndrome tumor bearing CI group, and the cold syndrome tumor bearing CI group, respectively. The weight and volume of rats' subcutaneous tumor were measured 14 days after tumor inoculation.</p><p><b>RESULTS</b>The weight and volume of tumor in the heat syndrome tumor bearing CI group [(3.55 +/- 1.12) g, (2864.44 +/- 1430.51) mm3] and the tumor bearing CI group [(4.29 +/- 1.14) g, (3397.19 +/- 1701.13) mm3] were significantly lower than those of the tumor bearing control group [(6.01 +/- 2.45) g, (6218.91 +/- 3837.64) mm3] and the cold syndrome tumor bearing CI group [(6.90 +/- 1.57) g, (6168.42 +/- 2457.03) mm3], showing statistical difference (P<0.05). There was insignificant difference among other groups.</p><p><b>CONCLUSIONS</b>CI showed better tumor inhibition effects on tumor bearing rats of heat syndrome constitution, which indicated CI was of cold property. It might be possibly used in tumor bearing rats of heat syndrome constitution.</p>

Prognostic analysis of transarterial chemoembolization combined with a traditional Chinese herbal medicine formula for treatment of unresectable hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang (JDF) granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival.</p><p><b>METHODS</b>A retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients (control group) received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc.</p><p><b>RESULTS</b>The median overall survival was 9.2 months (95% CI: 6.94 - 11.46) in the study group versus 5.87 months (95% CI: 4.21 - 7.52) in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows: serum hepatitis B surface antigen (HBsAg) (P = 0.014), maximum tumor size (P = 0.027), number of lesions (P < 0.001), portal vein invasion (P < 0.001), and the therapy model (P = 0.006).</p><p><b>CONCLUSION</b>Combination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.</p>