A Meta-analysis of Dachaihu Decoction combined with western medicine in the treatment of acute pancreatitis with the TCM syndrome of liver qi depression and liver-gallbladder dampness-heat

Backgroud:To evaluate the clinical efficacy and safety of Dachaihu Decoction in the treatment of acute pancreatitis(AP)with the traditional Chinese medicine(TCM)syndrome of liver qi depression and liver-gallbladder dampness-heat.Methods:We searched randomized controlled trials of Dachaihu Decoction in the treatment of AP with the TCM syndrome of liver qi depression and liver-gallbladder dampness-heat from databases in CNKI,WanFang,VIP,Embase,PubMed,and Cochrane Library(from established to August 2019).All the retrieved documents were imported into the Noteexpress software for screening and management,and the included documents were evaluated for quality and data extracted.Statistical analysis was performed with RevMan(version 5.3).Results:A total of 132 articles were retrieved and 8 studies were included to analysis,including 679 patients.Quality evaluation of included studies suggested that the quality of the literatures is generally not high.Meta-analysis showed that the total clinical effective rate of AP was higher in the treatment group than in the control group[OR=5.00,95%CI(2.86,8.73)],and the difference was statistically significant(P<0.00001).The patient's abdominal pain relief time[MD=-0.57,95%CI(-0.86,-0.27),P=0.0002],bloating relief time[MD=-0.71,95%CI(-1.05,-0.37),P=0.04],time of serum amylase returning to normal[MD=-1.00,95%CI(-1.60,-0.40),P=0.001]and time of urinary amylase returning to normal[MD=-1.62,95%CI(-2.88,-0.37),P=0.01]all lower than the control group.But there was no statistically significant difference between the treatment group and the control group at the first defecation time[MD=-0.86,95%CI(-1.75,-0.03),P=0.06].The patient's serum TNF-a levels on the 3rd[MD=-28.53,95%CI(-49.57,-7.49),P=0.008]and 7th day[MD=-26.13,95%CI(-49.76,-2.50),P=0.03]in the treatment group were statistically lower in the treatment group than in the control group.Similarly,the patient's serum IL-6 levels on the 3rd[MD=-6.62,95%CI(-12.49,-0.75),P=0.03]and 7th day[MD=-11.98,95%CI(-22.25,-1.71),P=0.02]were also statistically lower in the treatment group than in the control group.No serious complications or adverse reactions were observed.Conclusion:Dachaihu Decoction combined with western medicine in the treatment of AP with the TCM syndrome of liver qi depression and liver-gallbladder dampness-heat can improve clinical efficacy compared with western medicine alone.In addition,the combination therapy method is safe and can be used for syndrome differentiation of AP patients in the clinic.

Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Effective Common Chinese Herbal Medicines Used in Treating Chronic Cholecystitis with Liver-Gallbladder Dampness-Heat Syndrome: A Review of Clinical Studies in the Past 10 Years

The objective of the study is to identify the effective common Chinese herbal medicines used in treating chronic cholecystitis with liver-gallbladder dampness-heat syndrome(CCLGDHS) through reviewing relevant clinical studies published in the past 10 years. Data were collected from Science Direct and Chinese National Knowledge Infrastructure. Data screening was carried out for the abstracts and full texts of the data. The top 15 Chinese herbal medicines with the highest occurring frequency were selected, statistically analyzed, and classified by their medicinal properties, actions, and indications according to the Chinese Pharmacopoeia 2015 edition. The top 15 effective common Chinese herbal medicines comprise Chai Hu, Huang Qin, Jin Qian Cao, Bai Shao, Yin Chen, Yu Jin, Chuan Lian Zi, Yan Hu Suo, Zhi Shi, Ban Xia, Bai Zhu, Pu Gong Ying, Gan Cao, Zhi Zi, and Qing Pi. The predominant natures were cold, cool, and warm. This combination can clear stagnant heat, warm Yang, and regulate Qi dynamics. In addition, bitter, pungent, and sweet were the predominant flavors. They can clear dampness-heat, regulate Qi dynamics to relieve cramps and pain, as well as tonify the deficiency. Along with entering the liver and gallbladder meridians, these herbal medicines also entered the spleen, stomach, and lung meridians to prevent potential disease transmission. The combinatorial medicinal actions of the effective common Chinese herbal medicine highlight the importance of the holistic concept of traditional Chinese medicine when treating CCLGDHS. In addition, the inclusion of activating blood to promote blood circulation, relieving cramps and alleviating pain, and tonifying the spleen and stomach represents a new finding in the treatment principle for CCLGDHS.

Dampness-Heat Accelerates DMBA-Induced Mammary Tumors in Rats

Objective： To investigate the impact of dampness-heat （DH） on the development of mammary tumors in 7,12-dimethylbenz（a）anthracene （DMBA）-induced rats. Methods： Forty rats were randomly divided into 3 groups in a randomized block design, including the control group （n=13）, DMBA group （n=14）, and DMBA plus DH group （n=13）. Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA （100 mg/kg） for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature （33.0 ± 0.5 ℃） and humidity （90% ± 5%） for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 （MMP-9） and tissue inhibitor of metalloproteinases 1 （TIMP-1） in serum, and the contents of tumor necrosis factor- α （TNF- α ） and interleukin （IL）-1β in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes. Results： Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TiMP-1, TNF- α and IL-1β, and contents of tumor tissue TNF- α and IL-1β （P〈0.05 or P〈0.01）. Conclusion： DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF- α and IL-1β in DMBA-induced rats.

Efficacy and Safety of Guihuang Formula in Treating Type Ⅲ Prostatitis Patients with Dampness-Heat and Blood Stasis Syndrome: A Randomized Controlled Trial

Objective: To observe the efficacy and safety of Guihuang Formula(GHF) in treating patients with type Ⅲ prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis. Methods: Sixty-six type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome were randomly divided into the treatment group(GHF) and the control group(tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score, Chinese Medicine Symptoms Score(CMSS), expressed prostatic secretions(EPS) and adverse events(AEs). Results: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups(P<0.05). The CMSS score decreased in both groups(P<0.05). The white blood cell(WBC) count decreased and lecithin body count increased in both groups(P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group(P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups(P>0.05). In addition, no serious AEs were observed. Conclusion: GHF is effective in treating type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs.(Registration No. ChiCTR1900026966)

Haoqin Qingdan Decoction(蒿芩清胆汤)and Ribavirin Therapy Downregulate CD14 and Toll-Like Receptor 4 in Febrile Disease with Dampness-Heat Syndrome in A Mouse Model

Objective： To evaluate the effect of Chinese medicine Haoqin Qingdan Decoction （蒿芩清胆汤, HQD） for febrile disease dampness-heat syndrome （FDDHS）. Methods： Forty mice were divided into four groups, including normal control, FDDHS （induced by Radix et Rhizoma Rhei recipe and influenza virus A1 FM1 model）, HQD, and the ribavirin groups （10 in each）. The normal control and FDDHS groups were administered normal saline. HQD and the ribavirin groups were administered HQD and ribavirin intragastrically once daily at a dose of 64 g/（kg.d） and 0.07 g/（kg.d）, respectively for 7 days. Lethargy, rough hair, diarrhea, tongue color and sole color were evaluated for pathological changes in morphology. The tongue and lung tissues were collected for histology. The CD14 and toll-like receptor 4 （TLR4） expression levels were measured using real-time quantitative polymerase chain reaction. Results： More than 80% of the FDDHS mice showed hypokinesia and lethargy, and pathological changes associated with rough hair, diarrhea, tongue color and sole color. With advanced treatment for 7 days, the thick greasy tongue fur of the HQD and ribavirin groups were thinner than that of the FDDHS group （P〈0.05）, and it was the thinnest in the ribavirin group as compared with that in other groups （P〈0.05）. The CD14 and TLR4 expression levels in the lung tissues of HQD and ribavirin groups significantly delined compared with the model group （P〈0.05 or P〈0.01）. CD14 was down-regulated more remarkably in the HQD group compared with the ribavirin group （P〈0.05）, whereas the converse was true with TLR4 （P〈0.05）. Conclusions： We established a FDDHS mouse model showing systemic clinical symptoms. Both HQD and ribavirin can inhibit the expression of CD14 and TLR4 in FDDHS mice, while the effect of ribavirin might be much more violent. The expression changes of CD14 and TLR4 consistently refers to lipopolysaccharide, the commonly and hotly inducing factor in FDDHS.

原发性肾小球疾病湿热证和尿MCP-1、IL-6关系临床观察

目的:观察慢性原发性肾小球疾病的患者,湿热和非湿热组尿MCP-1、IL-6之间有无差异,从而探讨湿热证和MCP-1、IL-6的关系。方法:纳入50例患者,进行临床观察,留取尿液样本,ELISA方法测尿液IL-6、MCP-1水平,使用SPSS18.0统计软件包进行中医证候以及临床资料IL-6、MCP-1的数据分析。结果:(1)原发性肾小球疾病湿热证发病率为68%,湿浊证占18%(9/50),血瘀证占26%(13/50);(2)原发性肾小球疾病湿热证患者较非湿热证患者尿MCP-1、IL-6水平高(P<0.05);结论:(1)原发性肾小球疾病邪实证中湿热证的发病率最高,(2)湿热证和肾脏的免疫发病机制可能存在关系,不仅包括细胞因子,还包括趋化因子。

龙胆泻肝汤合五味消毒饮治疗淋证(湿热下注)观察

目的:观察龙胆泻肝汤合五味消毒饮治疗淋证(湿热下注)的效果。方法:将符合纳入标准的96例患者分成治疗组和对照组,其中治疗组50例,用龙胆泻肝汤合五味消毒饮加减;对照组46例,用左氧氟沙星治疗。结果:治疗2周后治疗组治愈率为54.00%,总有效率为88.0%;对照组治愈率为32.61%,总有效率为69.57%。经卡方检验,两组治愈率(x2=4.455,P<0.05)和总有效率(x2=4.844,P<0.05)相比,差异均具有显著性。结论:龙胆泻肝汤合五味消毒饮加减治疗淋证(湿热下注)明显优于用左氧氟沙星治疗。

Effectiveness of Jinying capsule on pelvic inflammatory disease in patients with symptom pattern of damp and heat accumulation: a double-blinded, multicenter, randomized, placebo-controlled clinical trial

OBJECTIVE: To evaluate the therapeutic effectiveness and safety of Jinying capsule on pelvic inflammatory disease(PID) in patients with symptoms identified as the pattern of damp and heat accumulation in terms of Traditional Chinese Medicine(TCM).METHODS: We conducted a double-blinded, multicenter, randomized, placebo-controlled clinical trial which included 155 patients diagnosed with PID and identified as symptom pattern of damp and heat accumulation. They were randomly divided into experimental group(n = 78) and control group(n = 77) according to a random number table. The treatment lasted for a period of 28 d. The experimental group was given Jinying capsules and oral levofloxacin plus oral metronidazole for first 7 d.They continued with Jinying capsules and levofloxacin placebo and metronidazole placebo for another 7 d. For the remaining 14 d, they continued with Jinying capsules only. Whereas, the control group was treated with oral levofloxacin and metronidazole and Jinying capsule placebo for the first 14 d in the same way as the experimental group and then continued with Jinying capsule placebo only for the remaining 14 d. The clinical efficacy was assessed using McCormack scale, TCM symptom pattern scores, physicochemical indexes including white blood cell and erythrocyte sedimentation rate, C-reaction protein, smear of vaginal discharge,and pelvic ultrasound.RESULTS: Comparing McCormack scale between both groups after treatment, the difference in curative effect between both groups was significant (P = 0.0269). The cure rate of the experimental group and control group is 76.32% and 59.46% respectively at week 4. Comparing TCM symptom pattern scores between both groups before and after treatment, the differences in total effective rate were both significant(P < 0.05). The curative effect rate of experimental group is 2.63% and 13.70% of the control group at week 1(P = 0.0131), and73.33% of the experimental group and 56.94% of the control group at week 4(P = 0.0369). No significant differences were found between the two groups on the Physicochemical indexes(all P >0.05). No adverse events or reactions occurred in the experimental groups.CONCLUSION: Jinying capsule can reduce the dosage of antibiotics needed for PID treatment, and improve the symptoms in PID patients.

Ultrastructure Characteristics of Different Chinese Medicine Syndromes of Helicobacter pylori-Correlated Gastric Diseases

Objective: To explore the ultrastructure characteristics of patients with dampness-heat of Pi(Spleen)-Wei(Stomach) syndrome(DHPW) and Pi-qi deficiency syndrome(PQD), both of which are Helicobacter pylori(Hp)-correlated gastric diseases(HPCG), and implicate a helpful hint for the clinical microcosmic syndrome differentiation. Methods: Fourteen gastric mucosa samples from 6 chronic gastritis(CG) and 6 active peptic ulcer(including 8 DHPW, 4 PQD) as well as 2 healthy volunteers were collected and tested for Hp infection. The ultrastructure of gastric mucosa was observed under the transmission electron microscope(TEM). Results: Among 14 gastric mucosa samples, 8 of them were Hp positive(6 DHPW and 2 PQD), which were all accordance with the results screened by supermicro-pathological method. Under TEM, the normal gastric mucosa, with tidy microvilli and abundant in mucus granules, mitochondria and rough endoplasmic reticulum distributed evenly, and with smooth nucleus membrane. But in those specimens of DHPW with Hp infection, microvilli were presented with burr shape. Especially, those samples from dampnessheat syndrome with predominant heat type(DHSH) patients were more obvious, with microvilli damaged, mitochondria concentrated and distributed in disorder, secretory tubule extended. In dampness-heat syndrome with predominant dampness type(DHSD) patients, mucus granules aggregated obviously, mitochondria swelled and blurred, and rough endoplasmic reticulum crowded. For 2 samples of DHPW without Hp infection, their microvilli were intact, with mitochondria increased and gathered but well-distributed, and secretory tubule extended mildly. In 2 PQD patients with Hp positive, the specimens of microvilli were sparse, and their mucus granules and mitochondria were decreased, with fractured crests and vacuole, secretory tubules extension to nucleus membrane, and rough endoplasmic reticulum extension in a pool-like way, and nucleus condensed. The 2 samples from PQD patients without Hp infection were characterized with intact microvilli, decreased mitochondria, fractured crest and extended rough endoplasmic reticulum in a pool-like way. Conclusion: It is obvious different in ultrastructure of DHPW and PQD patients under TEM, which may give a helpful hint for the microcosmic syndrome differentiation of HPCG.

Effect of Sanhuangyilong decoction plus methotrexate on tumor necrosis factor alpha and interferon gamma in serum and synovial fluid in rheumatoid arthritis patients with symptom pattern of damp heat obstruction

OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate(MTX) on Interferon gamma(IFN-γ) and tumor necrosis factor alpha(TNF-α) in the serum and synovial fluid of rheumatoid arthritis(RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of RA.METHODS: RA inpatients with damp-heat-obstruction symptom pattern(partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis(OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups:one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay(ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) and disease activity score in 28 joints(DAS28)were determined.RESULTS: Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat-obstruction symptom pattern were higher than those in healthy control group(P < 0.05).The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those in the serum of the RA patients(P < 0.05). The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those of the sy-novial fluid of the osteoarthritis patients(P < 0.05).The expression of TNF-α and IFN-γ in the serum and synovial fluid of the RA patients had no correlation with the inflammatory activity index ESR, CRP,or DAS28(P > 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group had increased, although the difference was not statistically significant(P > 0.05); in contrast, ESR, CRP, and DAS28 decreased, and the difference was statistically significant(P < 0.01). After 4 weeks of therapy, TNF-alpha and IFN-γ, ESR,CRP, and DAS28 in the combined group decreased compared with the before-treatment levels(P <0.01). After 2 w of treatment, the differences in the TNF-α and IFN-γ expression levels in the combined group were not statistically significant(P > 0.05)compared with that in the MTX group, although there were statistically significant differences in the ESR, CRP, and DAS28(P < 0.05). After 4 weeks of treatment, differences in TNF-α, IFN-γ, ESR, CRP, and DAS28 in the combined group compared with MTX group were statistically significant(P < 0.01).CONCLUSION: TNF-α and IFN-γ might be involved in the development of RA. The RA patients with damp-heat-obstruction symptom pattern show better benefits from the treatment of Sanhuangyilong decoction plus MTX, and the treatment is superior to that of using MTX only.