BackgroundAnthracycline-induced cardiotoxicity is a major factor affecting the long-term prognosis of cancer patients. Atrial arrhythmias, as common manifestations of cardiotoxicity, significantly impair quality of life and may compromise the effectiveness of anticancer therapy, representing a significant clinical challenge. Wenxin Keli (WXKL), a traditional Chinese medicine formulation with the effects of replenishing qi, nourishing yin, and promoting blood circulation, has demonstrated potential anti-arrhythmic benefits. However, high-quality evidence supporting its application in the field of cardio-oncology remains limited. This study aims to systematically evaluate the efficacy and safety of WXKL in patients with anthracycline-induced atrial arrhythmias.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 152 eligible participants will be enrolled and randomly assigned to receive either WXKL or placebo for 3 months, followed by a 3-month follow-up period. The primary outcome is the proportion of patients free from atrial arrhythmias at 3 months, defined as the absence of atrial fibrillation (AF) episodes lasting ≥30 s or premature atrial contractions (PACs) ≥100 beats per 24 h on Holter monitoring. Secondary outcomes include AF burden, PACs count, echocardiographic parameters, cardiac biomarkers (cTnI and NT-proBNP), quality of life (FACT-G), functional status (ECOG), clinical symptom scores, and anxiety scores (SAS) at 3 and 6 months, as well as safety assessments.DiscussionThis study is designed to provide high-level clinical evidence for the use of WXKL in the treatment of anthracycline-induced atrial arrhythmias. By incorporating both PACs and AF as a composite endpoint, the study aims to more comprehensively capture the overall burden and dynamic progression of atrial arrhythmias, and to inform cardio-protective strategies during cancer therapy.Trial registration:http://itmctr.ccebtcm.org.cn/zh-CN, International Traditional Medicine Clinical Trial Registry Platform, ITMCTR2025000704.

Depression(major depressive disorder, MDD) and Alzheimer's disease(AD) are two highly prevalent neuropsychiatric disorders. With the aging population, their comorbidity rate continues to rise. The pathogenesis of MDD and AD is complex, and modern medicine still lacks strategies that can simultaneously intervene in the core processes of both diseases. The theory of "treating different diseases with the same method" in traditional Chinese medicine(TCM) is an important therapeutic principle, which means that different diseases showing identical syndromes during their development can be treated with the same approach. This provides a TCM perspective for the diagnosis and treatment of their comorbidity. Based on the theory of the "liver-spleen-kidney" axis, this study identified that MDD and AD shared common pathogenesis: liver dysfunction in free coursing, spleen dysfunction in transportation, and kidney essence deficiency. It further connected this pathogenesis with the dysregulation of the neuroendocrine-immune(NEI) network in modern medicine, revealing common pathological mechanisms in neuroinflammation, dysfunction of the "hypothalamic-pituitary-adrenal"(HPA) axis, and gut microbiota dysbiosis. Meanwhile, it also reviewed specific mechanisms of TCM herbs such as Bupleuri Radix(Chaihu), Paeoniae Radix Alba(Baishao), and Astragali Radix(Huangqi), as well as their active components, in treating MDD and AD by regulating the NEI network through multiple targets and pathways. This may provide evidence for the application of the "treating different diseases with the same method" theory and broaden the perspective for the treatment of MDD and AD.

Osteoporosis(OP) is a metabolic bone disorder characterized by reduced bone mass and degenerative bone tissue. Osteoporotic pain(OPP) is its most common clinical symptom, significantly affecting the quality of life of patients. With the limitations of modern medical treatments and the intensification of aging, it is imperative to explore more cost-effective interventions for OPP. This paper, based on databases such as China National Knowledge Infrastructure(CNKI), VIP, Wanfang, BioMed, and Web of Science, uncovered the connection between the pathogenesis of OPP in traditional Chinese medicine(TCM) and modern medical mechanisms and retrospectively summarized the basic and clinical research methods and evidence of TCM prescriptions in the treatment of OP and related pain diseases. Studies have shown that TCM prescriptions, focusing on treatments such as nourishing the kidney, strengthening the spleen, and activating blood circulation to remove blood stasis, can significantly improve pain symptoms, increase bone mineral density(BMD), and adjust bone metabolic indicators such as C-terminal telopeptide of type Ⅰ collagen(CTX), serum bone Gla-protein(S-BGP), and alkaline phosphatase(ALP). The mechanisms of action of TCM prescriptions in treating OP and improving OPP symptoms were related to signaling pathways such as Wnt/β-catenin, nuclear factor kappa-B(NF-κB), mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and the osteoprotegerin(OPG)/receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand(RANKL) axis. Further strengthening the accumulation and analysis of clinical data, rigorously designing and conducting randomized controlled trials of TCM treatments for OPP with large sample sizes, standardizing outcome measures in basic and clinical research by using methods such as the core outcome set(COS), and incorporating mass spectrometry and omics approaches to uncover more potential active components and mechanisms may contribute to a deeper exploration of the advantages and essence of TCM prescriptions in the treatment of OPP.

In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.

Importance:Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective:To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants:This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions:Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures:The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results:Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance:In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration:Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.

Objective:To investigate the clinical effect on functional dyspepsia differentiated as liver-stomach disharmony treated with acupoint application of Chinese herbal medicine and wax therapy on the basis of Professor TIAN Conghuo's theory, "regulating qi movement". Methods:A total of 120 patients with functional dyspepsia of liver-stomach disharmony were randomly assigned to a combined therapy group (30 cases, 1 case dropped out), an acupoint application group (30 cases, 1 case dropped out), a wax therapy group (30 cases, 1 case dropped out) and a basic therapy group (30 cases, 2 cases dropped out). In the basic therapy group, omeprazole magnesium enteric-coated tablets were administered orally, 20 mg each time, once daily. Besides the treatment as the basic therapy group, the Chinese herbal acupoint application was used at Zhongwan (CV12) and Shenque (CV8) in the acupoint application group, and remained for 4 h in each intervention; and in the wax therapy group, wax therapy was delivered at the sites of Zhongwan (CV12) and Shenque (CV8) of the abdominal region and remained for 20 min in each intervention; and in the combined therapy group, the acupoint application was combined with wax therapy, administered once every other day or every two days, 3 times weekly. The duration of treatment was 4 weeks in the four groups. Before and after treatment, the score of main symptoms, the score of 36-item short-form health survey (SF-36) and the score of liver-stomach disharmony pattern were observed; and the clinical effect was evaluated in the four groups. Results:After treatment, regarding main symptoms and liver-stomach disharmony pattern, the score of every item was lower than that before treatment in the 4 groups (P<0.01). The score for each dimension in SF-36 was higher than that before treatment in the combined therapy group and the acupoint application group (P<0.01, P<0.05). In the wax therapy group, the scores for physiological activities, bodily pain, general health, vitality, social activities and mental health in SF-36 were higher than those before treatment (P<0.01, P<0.05). In the basic therapy group, the scores for physiological performance, bodily pain, general health and mental health in SF-36 were higher than those before treatment (P<0.05, P<0.01). After treatment, in the combined therapy group, the score for gastric distension and discomforts was lower than those of the basic therapy group and the wax therapy group (P<0.01), and the scores for gastric fullness in the morning, pain in the upper abdominal region and burning sensation in the upper abdominal region, as well as the score for liver-stomach disharmony pattern were lower than those in the rest 3 groups (P<0.01, P<0.05). In the combined therapy group, the scores for physiological activities, physiological performance, and bodily pain were higher than those of the basic therapy group (P<0.01, P<0.05), the scores for physiological activities and bodily pain were higher when compared with those in the acupoint application group (P<0.01, P<0.05) and the scores for physiological activities and vitality were higher when compared with those in the wax therapy group (P<0.05). After treatment, the score for each item of main symptoms, the score for liver-stomach disharmony pattern in the acupoint application group, and the score for liver-stomach disharmony pattern in the wax therapy group were all lower in comparison with those in the basic therapy group (P<0.01, P<0.05). The total effective rates was 93.3% (28/30), 73.3% (22/30), 66.7% (20/30) and 50.0% (15/30) in the combined therapy group, the acupoint application group, the wax therapy group and the basic therapy group, respectively; and the total effective rate in the combined therapy group was superior to the other 3 groups (P<0.01); the total effective rates in the acupoint application group and the wax therapy group were higher than that in the basic therapy group (P<0.01). Conclusion:The combination of acupoint application with Chinese herbal medicine and wax therapy, based on Professor TIAN Conghuo's theory of "regulating qi movement", can effectively treat functional dyspepsia, alleviate main symptoms and improve the quality of life in the patients.

Abstract Background: Traditional Chinese medicine paraffin therapy (TCMPT), a combination therapy of herbal acupoint application therapy and paraffin therapy, has demonstrated great effectiveness in treating some diseases. However, there is no relevant research in the treatment of functional dyspepsia (FD) with TCMPT.Using a randomized controlled trial, we investigate whether TCMPT is effective in improving Clinical-Assessment–FD symptoms (SCA-FD), in comparison with herbal acupoint application therapy, paraffin therapy and basic treatment. Further more, this study is also interested in changes of psychological status in patients with FD before and after TCMPT. Methods: This trial will be conducted in the Guang’anmen Hospital of China Academy of Chinese Medical Sciences in China. 120 FD patients will be randomized to one of the four arms of the trial: (1) TCMPT group, (2) Herbal acupoint application therapygroup, (3) Paraffin therapy group, and (4) Basic treatment group. The experimental phase will last 4 weeks,followed by a 2-week and 4-week follow-up period. During the 4-week treatment period, all the patients included will be treated with basic treatment (Omeprazole Magnesium Enteric-coated Tablets of 20mg, take orally, once daily for 4 weeks). In addition to basic treatment, patients in the TCMPT group will be treated with TCMPT, herbal acupoint application therapy group will be treated with herbal acupoint application therapy, paraffin therapy group will be treated with paraffin therapy (the treatment of each group will be applied 3 times a week, once every 1-2 days, for 4 weeks). The primary outcome are changes in the SCA-FD from baseline to the end of 4-week intervention. The secondary outcome measures are changes in the SCA-FD at other time points, Hospital Anxiety Depression Scale (HADS), Perceived Stress Scale (PSS), Short Form 36-item Health Survey (SF-36), and Changes of skin temperature at selected acupoints. Laboratory tests and adverse events also will be recorded. Discussion: If effective, this study will provide evidence for TCMPT in improving FD symptoms and mental health state of FD patients, and confirm that the effectiveness of TCMPT is better than herbal acupoint application therapy and paraffin therapy alone. The findings from this trial could be used to design new research protocols. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200061950, registered on 13 July 2022.

INTRODUCTION:Smoking prevalence is disproportionately higher in those with psychiatric symptoms. Smokers with psychiatric symptoms are less likely to have an intention to quit smoking and attain eventual smoking abstinence. This study presents the relationship between depressive/anxiety symptoms and the intention to quit smoking and related influencing factors.METHODS:A cross-sectional study recruited 931 current smoking individuals covering two provinces in China in July 2022. The online survey comprised questions concerning sociodemographic characteristics, smoking conditions and psychiatric symptoms. Chi-squared analyses and moderation analyses were applied.RESULTS:The proportion of smokers who had the intention to quit smoking within six months was 46.1%. In comparison with subjects without depressive/anxiety symptoms, individuals who had both psychiatric symptoms were less likely to have the intention to quit smoking (39.3% vs 49.8%, χ2=9.130, p=0.028). As for the moderating model of depression, the interaction term of depressive symptoms and smoking regularly was significant (β=0.554, t=3.260, p=0.001). For those who were occasional smokers, depressive symptoms significantly lowered their quitting intentions. The regularity of smoking similarly moderated the effect of anxiety symptoms on quitting intentions. When the number of cigarettes used weekly served as the moderator, the interaction of this number and depressive symptoms was significant, as well as for anxiety (p<0.001), indicating that the volume of cigarette consumption moderated the relationship between depressive/anxiety symptoms and intention to quit smoking.CONCLUSIONS:Psychiatric symptoms were significant factors in reducing the willingness of smokers to quit smoking, and the effects were moderated by smokers' cigarette consumption conditions. Interventions are urged to enhance quitting intentions of these vulnerable smokers.

Introduction Hypertension is one of the most important risk factors for cardiovascular disease, and its control rates remain low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) could suppress ventricular hypertrophy and inflammatory responses, lower blood pressure, and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension. Methods and analysis This trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experimental group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is the change in 24-h average systolic and diastolic blood pressure. The secondary outcomes include heart rate variability, pharmacogenomic evaluation, improvement in TCM syndrome, and serum pro-inflammatory/anti-inflammatory cytokines between the two groups. The safety of medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0. Ethics and dissemination This study has been approved by the Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial, and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences. Discussion We hypothesize that patients with low-to-medium-risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians. Trial registration Chinese Clinical Trial Registry ChiMCTR1900002876. Registered in November 2019

External therapy of traditional Chinese medicine and paraffin therapy are both traditional Chinese forms of treatment. In recent years, external use of traditional Chinese medicine combined with paraffin therapy, which involves combining meridians, acupoints, drugs, and hyperthermia, has demonstrated great effectiveness in treating certain conditions. An overview of traditional Chinese medicine paraffin therapy (TCMPT) is provided by this article. Additionally, this article describes a new classification of TCMPT, mechanism of action, clinical treatment, indications contraindications and adverse events reports.

YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of interferon gamma (IFNg) to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.

BACKGROUND AND PURPOSE:Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD. METHODS:The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively. RESULTS:A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05). CONCLUSION:In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.

目的 补肾降压方是临床基于补肾治则治法而形成的降压验方,其降压效果显著,但具体作用机制不明,探讨补肾降压方治疗高血压的作用机制.方法 根据药代动力学参数,通过中药系统药理学数据库与分析平台(TCMSP)数据库搜索、筛选补肾降压方药物活性成分,运用Pharm Mapper预测其作用靶点,利用Cytoscape软件构建补肾降压方活性成分-靶点相互关系网络.在Drugbank数据库和TTD数据库中以"hypertension"为关键词搜索疾病相关靶点,通过DAVID进行基于京都基因与基因组百科全书(KEGG)通路富集分析补肾降压方靶点,探究补肾降压方活性成分的作用机制.结果 得到补肾降压方活性成分93个,核心靶标566个,其中直接靶标50个,如肾上腺素受体、腺苷受体、内皮素受体、一氧化氮合酶、葡萄糖激酶等;涉及机制包括调节血管内皮功能、调节钙钠离子转运、调节糖脂代谢等.结论 补肾降压方通过参与血管舒张、调节离子转运、改善胰岛素抵抗、调节机体代谢等,参与病理过程不同环节,进而达到治疗高血压的临床疗效,为阐释该方的作用机制提供了参考.

Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.

Chinese herbal medicine has been increasingly used for patients with postmenopausal hypertension in China. A comprehensive literature search was performed in 7 electronic databases from their inception up to December 17, 2017 to examine the efficacy and safety of Chinese herbal medicine for postmenopausal hypertension. Thirty-nine randomized controlled trials involving 3, 823 participants were included. Meta-analyses favored Chinese herbal medicine plus antihypertensive drugs on blood pressure, blood pressure variability, postmenopausal symptoms, quality of life, and hormone levels compared with antihypertensive drugs. No severe adverse effects were identified. Er-xian decoction was the most frequently prescribed herbal formula, while Rehmannia glutinosa Libosch. was the most commonly used single herb. Chinese herbal medicine as complementary therapy maybe beneficial for postmenopausal hypertension. However, the effectiveness and safety of the decoction are still uncertain due to methodological shortcomings. Well-conducted trials are warranted to resolve the issue.

We have read with interest the paper by Guglin et al. [(1)][1] published recently in the Journal . In this trial, the study suggested that in high-risk patients who were going through an anthracycline-containing treatment, an active prevention can be used early and accurately to reduce the

YIV-906 (PHY906) is inspired by a traditional 1800-year Chinese herbal formulation, “Huang Qin Tang”, which is commonly used for treating diarrhea. Following chemotherapy and radiation, preclinical and clinical results suggest that YIV-906 has the potential to improve the patient’s quality of life and prolonging survival. Consistent preparations of PHY906 could be manufactured apart 15 years. The effects of YIV-906 were studied on the anti-tumor activity of anti-PD1 using BDF1 mice bearing Hepa 1-6 tumors. Results indicated that anti-PD1 alone had moderate effects on tumor growth however YIV-906 plus anti-PD1 eradicated all tumors in all tumor bearing mice. Further re-implantation of Hepa 1-6 cells did not grow in the “cured” mice, but implanted CMT167 (non-small lung carcinoma) cells or Pan02 (Pancreatic Ductal Adenocarcinoma) cells did grow; suggesting that YIV-906 plus anti-PD1 created a tumor-specific vaccine-like effect. The combination treatment exhibited a highly inflamed tumor microenvironment with more M1-like macrophage expression over M2. In culture YIV-906 could potentiate the action of IFNg (interferon gamma) to polarize bone marrow-derived macrophages (BMDM) into M1 macrophages while inhibiting IL4 action for M2 macrophage polarization. YIV-906 potentiated IFNg action through: 1) stimulating IFNg secretion, 2) phosphorylation of JAK1/2 and STAT1 and 3) increasing IRF1 protein expression. Scutellaria baicalensis Georgi (S) and its flavonoids of YIV-906 were responsible for potentiate the IFNg to polarize macrophage into M1. In conclusion, YIV-906 enhanced the anti-tumor activity of anti-PD1 by enhancing inflammation in the tumor microenvironment and enriching M1-like macrophages. This suggests the potential use of combination YIV-906 and anti-PD1 in cancer treatment. This work was supported by grant (1PO1CA154295-01A1) from National Cancer Institute (NCI), NIH, USA. Dr. Yung-Chi Cheng is a fellow of National Foundation for Cancer Research (NFCR), USA.Citation Format: Wing Lam, Xiaochen Yang, Zaoli Jiang, Xue han, Fulan Guan, Rong Hu, Chang-Hua Xu, Wei Cai, William Cheng, Shwu-Huey Liu, Yuping Cai, Nicholas Rattray, Caroline Johnson, Lieping Chen, Yung-chi Cheng. YIV-906 (PHY906) enhanced the anti-tumor activity of immune checkpoint blockade therapy (Anti-PD1) against liver cancer by changing the tumor micro-environment associated with M1 macrophages infiltration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2252.

With a rapidly aging population, the prevalence of hypertension in adults continues to rise, placing a substantial and escalating social and economic burden. Ilex hainanensis Merr. is commonly used as a folk remedy for treating hypertension, dyslipidemia, and inflammation in China. This systematic review aims to evaluate current evidence for the therapeutic effect of Ilex hainanensis Merr. extract (EIH) on essential hypertension. Six electronic databases (Pubmed, MEDLINE, The Cochrane Central Register of Controlled Trials, Chinese Scientific Journals Database, Wanfang and CNKI) were searched to identify eligible randomized controlled trials (RCTs) relevant to EIH on essential hypertension up to Jan 2018. Six RCTs including 772 participants met eligibility criteria. Methodological quality of the trials was generally low. Meta-analysis showed that EIH demonstrated a beneficial effect for lowering systolic and diastolic blood pressure (SBP/DBP), left ventricular mass (LVM) in participants with essential hypertension. There was no significant difference between EIH and antihypertensive drugs in SBP (WMD: -0.44 [-2.30, 1.43]; P = 0.65), DBP (WMD: WMD: -0.02 [-1.13, 1.09]; P = 0.98) and LVM (WMD: -1.36 [-4.99, 2.26]; P = 0.46). Moreover, one trial showed that EIH combined with antihypertensive drugs was more effective in lowering blood pressure than those antihypertensive drugs used alone. However, the findings were limited by the small sample sizes, duration and low methodological quality of the trials. This is the first systematic review of EIH on essential hypertension. More rigorous RCTs with high quality are still needed to prove the effectiveness and safety of EIH and its preparations for essential hypertension.

Background: The traditional Chinese medicine classic herbal formula Longdanxiegan decoction (LDXGD) is widely used for hypertensive patients in China. Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of LDXGD for hypertension. Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang Database were searched up to February 7, 2017 for randomized control trials in treating hypertension. Results: Nine trials were identified. Compared with antihypertensive drugs, Longdanxiegan decoction plus antihypertensive drugs (LPAD) significantly improved systolic blood pressure (BP) (n = 138; MD = -4.82 mmHg; 95% CI: -7.89 to -1.76; P = 0.002), diastolic BP (n = 138; MD = -2.42 mmHg; 95% CI: -3.22 to -1.62; P < 0.00001), categorical BP (n = 509; RR: 1.26; 95% CI: 1.17 to 1.36; P < 0.00001), hypertension related symptoms (n = 509; RR: 1.31; 95% CI: 1.15 to 1.49; P < 0.0001), and heart rate (n = 138; MD = -2.40 bpm; 95% CI: -4.23 to -0.56; P = 0.01). Beneficial effects but no statistically significant reduction in total cholesterol (n = 138; MD = -0.11 mmol/l; 95% CI: -0.65 to 0.44; P = 0.71), or triglyceride (n = 138; MD = -0.20 mmol/l; 95% CI: -0.46 to 0.07; P = 0.14) was observed in LPAD. Compared with antihypertensive drugs, LDXGD used alone significantly improved systolic BP, diastolic BP, and hypertension related symptoms. But there was no difference between LDXGD and antihypertensive drugs on categorical BP (n = 120; RR: 1.09; 95% CI: 0.96 to 1.23; P = 0.18). The safety of LDXGD were still unclear. Conclusions: Due to poor methodological quality of the included trials, as well as potential reporting bias, our review found no conclusive evidence for the effectiveness of LDXGD in treating hypertension. The potential beneficial effects and safety of LDXGD should be assessed in future properly designed trials.

Abstract Immune checkpoint blockade therapy has recently been recognized as a breakthrough in cancer treatment. Recently, FDA has approved Nivolumab (anti-PD1) for the treatment of hepatocellular carcinoma (HCC) patients previously treated with sorafenib. However, the percentage of patients with a complete response was only 1.9% that is much lower than Nivolumab used for treating melanoma. Diarrhea, nausea and fatigue are common side effects for HCC patients who received Nivolumab. YIV906(PHY906) is inspired by the Huang Qin Tang, which was first described in Chinese texts 1800 years ago for the treatment of numerous gastrointestinal symptoms. Consistent preparations of PHY906 can be manufactured apart 10 years. Our clinical results suggest that YIV906 has potential to increase the therapeutic index of capecitabine or sorafenib for HCC patient by improving quality of life and prolonging life. In animal studies, YIV906 can increase the anti-tumor activity of a broad spectrum of chemotherapies through multiple mechanism of actions. We believe that YIV906 could have potential to improve the efficacy of Nivolumab, either by increasing its anti-tumor activity or decreasing its side effects. Here, we studied the effect of YIV906 on the anti-tumor activity of anti-PD1 using BDF1 mice bearing with Hepa 1-6 tumors. Results indicated that YIV906 alone had only moderate effects on the Hepa 1-6 tumor growth. Anti-PD1 alone could stabilize 80% tumor growth and caused 20% tumor shrinkage following 8-day injection. YIV906 plus anti-PD1 made all tumors disappear following 7-day treatment and no tumor rebound was found for one month. When YIV906 and different dosages of anti-PD1 ( 70ug or 200ug per animal) were used, YIV906 plus anti-PD1 (70ug) had an stronger anti-tumor effect than anti-PD1 (200ug) alone. The above results suggested that YIV906 could reduce the usage of anti-PD1 by 3-fold while having better antitumor effects than anti-PD1 alone. qRT-PCR results recovered that many genes related to M1-like macrophages and T cell activation were strongly up-regulated in the tumor tissues following YIV906 plus anti-PD1 treatment. More macrophages were found in tumor tissues associated with an upregulation of MCP1 protein following YIV906 plus anti-PD1 treatment. Biostatical analysis, based on the mRNA expression of M1 and M2-like macrophage signature genes, suggested the tumor microenvironment was favorable for M1 status following YIV906 plus anti-PD1 treatment. In addition, YIV906 could decrease LPS-induced PD1 protein of macrophages in culture. In conclusion, YIV906 might enhance the anti-tumor activity of anti-PD1 by changing the tumor microenvironment favorable to M1-like macrophages. Our results provide supportive information to initialize HCC clinical trial with YIV906 plus Nivolumab. This work was supported by grant (PO1CA154295-01A1) from NCI, USA. Dr. Y.-C. C is a fellow of NFCR, USA. Citation Format: Wing Lam, XiaoChen Yang, Zaoli Jiang, Xue Han, Fulan Guan, William Cheng, Shwu-Huey Liu, Lieping Chen, Yung-Chi Cheng. YIV906 (PHY906) enhanced the antitumor activity of immune checkpoint blockade therapy: Anti-PD1 against liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2724.