Chinese Medicine Regulates Intestinal Flora to Treat Ulcerative Colitis in Patients with Syndrome of Large Intestine Dampness-heat： A Review / 中国实验方剂学杂志

The clinical changes of ulcerative colitis （UC） with the main syndrome of large intestine dampness-heat and the alterations of intestinal flora in UC were summarized to reveal the underlying mechanism. After review of the treatment methods for UC with the syndrome of large intestine dampness-heat， we identified the representative traditional Chinese medicines and compound prescriptions and explored the treatment mechanisms. Furthermore， we probed into the associations of UC and the treatment methods with the intestinal flora. The related articles were retrieved from China National Knowledge Infrastructure （CNKI）. The available studies have shown that Akkermansia muciniphila， Escherichia coli， Enterococcus， and probiotics such as Bifidobacterium and Lactobacillus are closely associated with Chinese medicines in UC patients with the syndrome of large intestine dampness-heat. However， due to the shortcomings in clinical research and the susceptibility of intestinal flora to diverse factors， it is still challenging to accurately characterize the intestinal flora changes associated with diseases. Additionally， the research on the mechanisms of Chinese medicines in regulating intestinal flora in UC patients with the syndrome of large intestine dampness-heat remains to be improved. The feasibility of using Chinese medicines and compound prescriptions for precise regulation of intestinal flora in these patients is still debatable. In this regard， scientific issues such as the biological connotation of UC with the syndrome of large intestine dampness-heat and the correlation between syndrome and intestinal flora have become primary research tasks. Additionally， attention should also be paid to the interactions between the intestinal lumen exposure profile of Chinese medicines and intestinal flora. Finally， the thinking of traditional Chinese medicine （TCM） and the concepts of modern medicine should be combined for the research on the formulation of TCM regimens for regulating intestinal flora in treating UC.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor / 中国结合医学杂志

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.

Mechanism of Ethyl Acetate Extract of Gentianopsis paludosa in Treatment of Ulcerative Colitis Based on Bcl-2/Bax Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of ethyl acetate extract of Tibetan medicine dampness bud Gentianopsis paludosa in the prevention and treatment of recurrent ulcerative colitis （UC） in rats with dampness-heat in large intestine syndrome based on the apoptotic pathway mediated by the B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. MethodUsing the disease-syndrome combination method， a recurrent UC model of dampness-heat in large intestine syndrome was constructed in rats. Seventy SPF-grade male SD rats were randomly divided into control group， model group， high-， medium-， and low-dose ethyl acetate of G.paludosa groups （150， 75， 37.5 mg·kg-1）， and mesalazine group （135 mg·kg-1）. The rats were orally administered with respective drugs for 14 days. The general conditions of the rats were recorded， and colon length and mucosal damage were observed. The colon wet weight index and organ coefficients of the liver， spleen， and thymus were calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β） in the serum of each group. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the colon. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect apoptosis in colonic epithelial cells. Western blot was used to measure the expression levels of Bcl-2， Bax， Caspase-3， Caspase-9， Zona Occludens-1 （ZO-1）， Claudin3， and Occludin in colonic tissue. Immunohistochemistry （IHC） was used to observe the expression of Bax and Caspase-3 in colonic epithelial cells. ResultCompared with the control group， the model group showed significant increases in the disease activity index （DAI） score， colonic mucosal damage index （CMDI）， intestinal epithelial apoptosis， liver and spleen indexes， and levels of inflammatory factors IL-1β and IL-6 in the serum （P<0.01）， decreased expression of intestinal mucosal protective proteins ZO-1， Claudin3， and Occluding （P<0.01）， increased expression of pro-apoptotic proteins Bax， Caspase-3， and Caspase-9 （P<0.01）， and decreased expression of anti-apoptotic protein Bcl-2 （P<0.01）. Compared with the model group， the high-， medium-， and low-dose ethyl acetate of G.paludosa groups all significantly improved the general condition of the rats， reduced colonic lesions， decreased intestinal epithelial cell apoptosis， reduced liver and spleen indexes， upregulated the expression of ZO-1， Claudin3， Occludin， and Bcl-2 proteins， and downregulated the expression of Bax， Caspase-3， and Caspase-9 proteins， with the high- and medium-dose ethyl acetate of G.paludosa groups showing the superior effects （P<0.05， P<0.01）. ConclusionEthyl acetate of G.paludosa can alleviate colonic mucosal damage and exert a therapeutic effect on UC by regulating the Bcl-2/Bax signaling pathway.

Correlation of traditional Chinese medicine to reduced re-admission risk in ankylosing spondylitis patients with dampness-heat syndrome: a retrospective cohort study / 中国中药杂志

This study aimed to analyze the impact of traditional Chinese medicine(TCM) on the risk of re-admission for ankylosing spondylitis(AS) patients with dampness-heat syndrome. In this study, a telephone follow-up was conducted on 1 295 AS inpatients, and after screening and exclusions, 1 044 successfully followed-up patients were included. A retrospective cohort study was conducted using propensity score matching(PSM), and a Cox proportional risk model was employed to assess the effect of various factors on the risk of re-admission for AS patients with dampness-heat syndrome. Kaplan-Meier survival curves were used to analyze the effect of TCM intervention time on re-admission. The incidence rate of dampness-heat syndrome in AS patients was found to be 51.3% in this study. After 1∶1 PSM, 385 AS patients with dampness-heat syndrome and 385 AS patients without dampness-heat syndrome were included for analysis. The results indicated that the re-admission rate was higher for patients with dampness-heat syndrome compared with those without dampness-heat syndrome(P<0.05). AS patients with dampness-heat syndrome in the TCM group had a lower admission rate than those in the non-TCM group(P=0.01). The cox proportional risk model demonstrated that TCM was an independent protective factor, as it reduced the risk of re-admission by 35%(HR=0.35, 95%CI[0.26, 0.95], P<0.05). Moreover, the subgroup with high exposure(time to use Chinese medicine >12 months) had a significantly lower risk of re-admission than that with low TCM exposure(time to use Chinese medicine ≤12 months). The re-admission rate for AS patients with dampness-heat syndrome was higher than that without dampness-heat syndrome, and TCM was identified as a protective factor in reducing the risk of re-admission. Furthermore, a longer duration of TCM intervention was associated with a lower risk of re-admission.

Mechanism of Dahuang Mudantang in Improving Pancreatic Injury in Rats with Acute Pancreatitis of Dampness-heat in Large Intestine Syndrome Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo reveal the intervention effect of Dahuang Mudantang on pancreatic injury in rats with acute pancreatitis （AP） of dampness-heat in large intestine syndrome and explore its possible mechanism based on network pharmacology. MethodNinety-six SPF-grade Wistar rats were randomly divided into the following six groups： a blank group， a model group， low-， medium-， and high-dose Dahuang Mudantang groups （3.5， 7， and 14 g·kg-1）， and a Qingyi Lidan granules group （3 g·kg-1）， with 16 rats in each group. The AP model of dampness-heat in large intestine syndrome was induced in rats except for those in the blank group by "high-temperature and high-humidity environment + high-sugar and high-fat diet + retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct". The blank and model groups received equal volumes of distilled water by gavage， while the treatment groups were administered Dahuang Mudantang or Qingyi Lidan granules 1 hour before modeling， and 12 and 24 hours after modeling. Samples were collected 1 hour after the last administration. The general conditions of the rats were observed. The AP model of dampness-heat in large intestine syndrome was evaluated. Serum amylase （AMS） and C-reactive protein （CRP） levels were determined using biochemical methods. Pancreatic tissue morphology was observed using hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict potential targets of Dahuang Mudantang in the intervention in AP， and molecular biology technique was used to verify relevant targets. ResultCompared with the blank group， the model group exhibited lethargy， unkempt fur， loose and foul-smelling stools， elevated anal temperature with arching and twisting reactions， significantly increased serum levels of AMS and CRP （P<0.05）， abnormal pancreatic ductules， disordered interlobular spaces， and inflammatory cell infiltration in histopathological examination， as well as pathological changes including pancreatic acinar cell swelling， congestion， and necrosis. Compared with the model group， the treatment groups showed varying degrees of improvement in general survival conditions， reduced twisting reactions， visibly improved stool characteristics， reduced pancreatic tissue edema and necrosis， decreased serum AMS and CRP levels （P<0.05）， with the high-dose Dahuang Mudantang group showing the most pronounced effects （P<0.05）. Network pharmacology prediction indicated that hederagenin， β-sitosterol， and quercetin were the most widely connected active compounds with disease targets. Protein-protein interaction （PPI） network analysis revealed that protein kinase B （Akt）， tumor protein P53 （TP53）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， transcription factor （JUN）， vascular endothelial growth factor α （VEGFα）， interleukin-1β （IL-1β）， and vascular cell adhesion molecule-1 （VCAM1） were key targets in the "drug-disease" interaction. KEGG enrichment analysis suggested that the response of the mitogen activated protein kinase （MAPK） signaling pathway might be a core mechanism for DHMDT in the intervention in AP. Molecular biology analysis showed that compared with the blank group， the model group had significantly increased levels of TNF-α， IL-6， and VCAM-1 in pancreatic tissue （P<0.05）， as well as significantly elevated expression levels of p38 mitogen-activated protein kinase （p38 MAPK）， mitogen-activated protein kinase-activated protein kinase 2 （MK2）， and human antigen R （HUR） genes and proteins （P<0.05）. Compared with the model group， the treatment groups exhibited decreased levels of TNF-α， IL-6， and VCAM-1 in pancreatic tissue （P<0.05）， reduced expression levels of p38 MAPK， MK2， and HUR genes and proteins， with the high-dose Dahuang Mudantang group showing the most pronounced effects （P<0.05）. ConclusionDahuang Mudantang activates and regulates the p38 MAPK/MK2/HUR signaling pathway to suppress the release of inflammatory factors， thereby improving pancreatic injury.

Therapeutic Effect of Modified Baqia Baweitang on Diabetic Foot Due to Dampness-heat Toxicity / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of modified Baqia Baweitang on diabetic foot due to dampness-heat toxicity. MethodOne hundred and four patients were randomized into control and observation groups （52 cases）. The control group was treated with epalrestat combined with Compound Huangbai Liquid， and the observation group with modified Baqia Baweitang on the basis of the therapy in the control group. The resting pain， intermittent claudication， foot cold feeling， traditional Chinese medicine （TCM） symptoms， ulcer area， ulcer surface pH， ulcer depth， and percutaneous oxygen partial pressure were measured before and after treatment. The blood glucose and lipid levels ［fasting blood glucose （FPG）， 2 h postprandial blood glucose （2 h PG）， triglyceride （TG）， and total cholesterol （TC）］， hemorheological indexes （peak blood flow， blood flow， vascular diameter， and pulse index）， motor and sensory nerve conduction velocity， and inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， IL-13， and C-reactive protein （CRP）］ in the serum and skin lesions were determined. The clinical efficacy and safety were compared between the two groups. ResultThe total response rate in the observation group was 96.2% （50/52）， which was higher than that （80.8%， 42/52） in the control group （χ2=6.029， P<0.05）. The treatment in both groups decreased the resting pain， intermittent claudication， foot cold feeling， TCM symptom scores， ulcer area， ulcer surface pH， and ulcer depth （P<0.05） and increased the percutaneous oxygen partial pressure （P<0.05）. Furthermore， the treatment lowered the levels of FPG， 2 h PG， TG， TC， blood flow peak， TNF-α， IL-6， IL-18， and CRP （P<0.05） and increased the blood flow， vascular diameter， pulse index， and the motor and sensory nerve conduction velocity （P<0.05）. Moreover， the changes in the above indexes were more significant in the observation group than in the control group （P<0.05）.The incidence of adverse reactions was 21.2% （11/52） in the control group and 23.1% （12/52） in the observation group， with no statistical significance. ConclusionModified Baqia Baweitang can promote wound healing， improve the dorsal artery hemorheology of feet， accelerate nerve conduction， and reduce inflammation in the patients with diabetic foot due to dampness-heat toxicity.

Research progress in the theoretical connotation and mechanism of the eliminating dampness-heat method for the treatment of chronic kidney disease / 国际中医中药杂志

This article aimed to explore the theoretical connotation and mechanism of clearing damp-heat method in the treatment of chronic kidney disease (CKD), provide theoretical support for clearing damp-heat method in the treatment of chronic kidney disease, and further explain the modern scientific connotation of "damp-heat impairing kidney". Modern Traditional Chinese Medicine (TCM) believes that damp-heat is an important pathogenesis of kidney damage. Clearing damp-heat method plays a key role in inhibiting CKD immune inflammatory response, improving oxidative stress and antagonizing renal fibrosis. The mechanism is mainly related to the regulation of TNF-α level, blocking NF-κB signaling pathway, inhibiting inflammatory cytokines, antagonizing TGF-β1 secretion and other pathways.

Study on the effects and mechanism of Guiling Gao on the activity state of rats with damp-heat syndrome / 国际中医中药杂志

Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.

Comparative Diagnosis Test Accuracy of Five Weighting Methods for Type 2 Diabetes Mellitus with Dampness-heat Syndrome / 中医杂志

ObjectiveTo compare the diagnostic accuracy of five different weighting methods of Chinese medicine syndrome and then analyze their diagnostic efficacy and characteristics， by taking Diagnostic Standard for Type 2 Diabetes Mellitus （T2DM） with Dampeness-heat Syndrome （abbreviated as diagnostic standard） as an example. MethodsData from expert questionnaire on the diagnostic standard and a cross-sectional survey of 1021 patients were collected. The comparative diagnostic test accuracy （CDTA） method was used to calculate the area under the ROC curve （AUC）， area under the PR curve （AUPR）， accuracy （ACC）， sensitivity， and specificity of five commonly used weighting methods in two categories， including knowledge-driven weighting methods （expert scoring synthesis method， analytic hierarchy process， and precedence chart method） and data-driven weighting methods （logistic regression contribution method and entropy weighting method）. ResultsAmong 1021 patients with T2DM， 389 cases were diagnosed as dampness-heat syndrome. The expert scoring synthesis method， analytic hierarchy process method， and precedence chart method were basically consistent in the weight scores of each item. The expert scoring comprehensive method， analytic hierarchy process method， and entropy weighting method have a smaller difference in the weight scores of each item， while there was larger difference in the weight scores of each item of the precedence chart method and the logistic regression contribution method. The AUC （95% CI）， AUPR， ACC， sensitivity， and specifi-city of the expert scoring synthesis method were 0.913 （0.893， 0.932）， 0.851， 0.870， 0.868 and 0.875， respectively； while those of the analytic hierarchy process method were 0.910 （0.890， 0.930）， 0.838， 0.879， 0.848 and 0.896； of the precedence chart method were 0.919 （0.900， 0.937）， 0.858， 0.875， 0.871 and 0.875； of the logistic regression contribution method were 0.867 （0.842， 0.891）， 0.792， 0.853， 0.769 and 0.898； and of the entropy weighting method were 0.895 （0.873， 0.916）， 0.820， 0.869， 0.802 and 0.908. ConclusionThe knowledge-driven weighting methods are better than the data-driven weighting methods in terms of diagnostic efficacy and reflecting expert experience.

Shaoyaotang Alleviates Ulcerative Colitis by Regulating Th17/Treg Balance Through IL-6/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the role of interleukin-6 （IL-6）/signal transducer and activator of transcription 3 （STAT3） pathway in the balance of T helper 17 （Th17）/regulatory T （Treg） cells in ulcerative colitis （UC） with internal dampness-heat accumulation syndrome and the intervention mechanism of Shaoyaotang. MethodA total of 60 SD rats were randomized into blank group （equivalent volume of normal saline）， model group （equivalent volume of normal saline）， western medicine control group （0.42 g·kg-1 mesalazine）， and low-dose （11.1 g·kg-1）， medium-dose （22.2 g·kg-1）， and high-dose （44.4 g·kg-1） Shaoyaotang groups. UC with internal dampness-heat accumulation syndrome was induced in rats with the compound method except for the blank group. The administration lasted 14 days for each group. At 24 h after the last administration， rats were killed and the spleen and colon tissues were separated. The histopathological changes of colon were observed based on hematoxylin and eosin （HE） staining and the levels of interleukin-17 （IL-17） and transforming growth factor-β1 （TGF-β1） in colon tissue were detected by immunohistochemistry （IHC）. Flow cytometry was employed to determine the levels of Th17/Treg cells in the spleen， and Western blot to measure the levels of IL-6 and STAT3 proteins in colon tissue. ResultCompared with the blank group， the model group had lesions such as congestion and erosion， low percentage of spleen Treg cells （P<0.01）， high percentage of Th17 cells （P<0.01）， and high levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. Compared with the model group， the administration groups showed alleviation of colon injury， high percentage of spleen Treg cells （P<0.05， P<0.01）， low percentage of Th17 cells （P<0.01）， and low levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. ConclusionShaoyaotang regulates the balance of Th17/Treg by inhibiting the IL-6/STAT3 pathway， thereby relieving the pathological damage of UC rats with internal dampness-heat accumulation syndrome and affecting their immune function.

Effect of Danggui Niantongtang on Intestinal Flora in Adjuvant-induced Arthritis Rats of Wind-dampness-heat Arthralgia：Based on 16S rDNA Sequencing / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNTT） against adjuvant-induced arthritis （AA） in rats with wind-dampness-heat arthralgia （FSR） based on the variation of intestinal flora. MethodA total of 60 SD rats were randomized into normal （control） group， FSR group， low-， medium-， and high-dose DGNTT （5.67， 11.34， 22.68 g·kg-1） groups， and methotrexate （MTX） group （1.35 mg·kg-1）， with 10 rats in each group. The rats， except the control group， were injected with Mtb adjuvant and then exposed to artificial climatic chamber （hot and humid with wind） for 64 h for modeling. The rats were treated with water， DGNTT or MTX for 28 days from the day of injection. Arthritis index （AI） of rats was measured and paw volume was determined with a volume meter. The morphology of synovial tissues of the knees was observed based on hematoxylin-eosin （HE） staining and the changes of intestinal flora were analyzed based on 16S rRNA sequencing. ResultDGNTT can alleviate the hyperplasia of synovial tissue and inflammation of AA rats with FSR and inhibit the formation of pannus. The results of 16S rRNA sequencing showed that the relative abundance of Firmicutes， Lactobacillus， Prevotella 9， and Alloprevotella decreased （P<0.05， P<0.01） and the relative abundance of Bacteroidetes and Bacteroides increased （P<0.01） in FSR group compared those in the control group. Compared with the FSR group， all DGNTT groups and MTX group had high relative abundance of Lactobacillus （P<0.05， P<0.01） and low relative abundance of Bacteroidetes （P<0.01） and medium-dose and high-dose DGNTT groups and MTX group showed high abundance of Firmicutes， Prevotella 9， and Alloprevotella and low abundance of Bacteroides （P<0.05， P<0.01）. Spearman's correlation analysis suggested that the abundance of Bacteroides and Helicobacter was in positive correlation with AI （P<0.05）， while the abundance of Prevotella 9 and Candidatus Saccharimonas was in negative correlation with AI （P<0.01， P<0.05）. There was a negative correlation between the abundance of Prevotella 9 and paw volume （P<0.01）， and the abundance of Ruminococcaceae NK4A214 group， Christensenellaceae R-7 group， and Bacteroides was in negative correlation with spleen index （P<0.05）. The abundance of Prevotella 9 was in negative correlation with spleen index （P<0.01）. ConclusionDGNTT is effective for arthritis with FSR， as it can regulate the composition of intestinal flora in AA rats by increasing the abundance of probiotics and inhibiting the growth of pathogenic bacteria. The mechanism is the likelihood that it improves intestinal immune metabolism to ensure intestinal homeostasis.

Clinical efficacy of umbilical therapy with herbal cakes of different dosages for damp-heat diarrhea in young children / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of umbilical therapy with herbal cakes made of Ge Gen Qin Lian Tang prescription of different dosages in treating damp-heat diarrhea in young children. Methods: Seventy-two kids with diarrhea of damp-heat pattern were recruited and divided into a high-dosage group and a low-dosage group using the random number table method, with 36 cases in each group. They all received conventional antidiarrheal treatment and umbilical application with herbal cakes. However, the herbal cakes for the high-dosage group were made of the mixture of Ge Gen Qin Lian Tang powder and water, and those for the low-dosage group consisted of 10％ Ge Gen Qin Lian Tang powder and 90％ auxiliary materials (corn starch) plus water. The treatment duration was 3 d. The clinical efficacy, antidiarrheal rate, effective rate for symptoms and signs of traditional Chinese medicine (TCM), TCM symptoms score, and safety indicators were compared between the two groups. Results: After the treatment, the TCM symptoms scores dropped significantly in both groups (P<0.01) and were lower in the high-dosage group than in the low-dosage group (P<0.05). The clinical efficacy was more significant in the high-dosage group than in the low-dosage group after the treatment, and the between-group difference was statistically significant (P<0.05); the antidiarrheal rate was markedly higher in the high-dosage group than in the low-dosage group (P<0.05). Regarding the TCM symptoms and signs, the high-dosage group showed better results in improving the greasy and yellowish tongue coating, bowel movement frequency, watery excrement, short and dark urine, red tongue body, red anus, vomiting, bowel sounds, and abdominal bloating compared with the low-dosage group, and the between-group differences were statistically significant (P<0.01). Conclusion: Umbilical therapy with herbal cakes made of Ge Gen Qin Lian Tang is safe, reliable, and effective in treating damp-heat diarrhea in young children; the high-dosage herbal cakes produce more significant efficacy than the low-dosage ones and are worth further investigation.

Discussion on Treatment of Diarrhea of Intestinal Dampness-heat Syndrome and of Cold-dampness Disturbing Spleen Syndrome with Different Methods： Based on Intestinal Microbiota Function / 中国实验方剂学杂志

ObjectiveTo study the changes of microbiota in different intestinal niches in the instance of diarrhea with intestinal dampness-heat syndrome and cold-dampness disturbing spleen syndrome， so as to provide objective evidence for treating diarrhea with different methods from the perspective of intestinal flora. MethodThe 16S rRNA gene high-throughput sequencing data of model mice with diarrhea of the two syndromes and the model mice after prescription intervention were retrieved from National Center for Biotechnology Information （NCBI）， and the intestinal dominant bacteria and microbial functions were compared among groups. Spearman's correlation coefficient among the microorganisms in each group was calculated and the co-occurrence networks of intestinal microbiota were constructed to study the interaction of the microbiota. ResultThe microbiota imbalance in intestinal contents of mice with diarrhea of intestinal dampness-heat syndrome was characterized by the enrichment of Muribaculum and Aerococcus， while the imbalance in intestinal mucosa was manifested by the enrichment of Gram-negative Neisseria， Capnocytophaga， and Prevotella （P<0.05）. However， after the treatment with Gegen Qinliantang， the microbiota in two distinct ecosystems was characterized by the enrichment of Lactobacillus and the abundance of Streptococcus in intestinal mucosa was increased. The microbiota imbalance in intestinal contents of diarrhea with cold-dampness disturbing spleen syndrome was characterized by the enrichment of Lactobacillus （P<0.01） and Clostridium sensu stricto 1， while the intestinal mucosa was dominated by the increase of Candidatus arthromitus and Enterobacter. However， after the treatment with Huoxiang Zhengqi powder， the intestinal contents were characterized by Lactobacillus enrichment， while the intestinal mucosal flora was featured by the enrichment of C. arthromitus， Pseudomonas， and Bacillus. Overall， the contribution of dominant bacteria in intestinal mucosa to the difference was higher than that in intestinal contents， and more dominant bacteria in the intestinal mucosa interacted with other bacteria. ConclusionMicrobiota imbalance is different for diarrhea of different syndromes， and the therapeutic effects of corresponding prescriptions are also different. In addition， the microbiota imbalance has different characteristics between intestinal niches for mice with diarrhea of the same syndrome. Therefore， intestinal flora may be one of the biological bases for exploring the characteristics of "treating the diarrhea with different methods" in Chinese medicine.

Mechanism of Danggui Niantongtang on Adjuvant Arthritis Rats with Wind-dampness-heat Arthralgia Based on Quantitative Proteomics / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNT） against adjuvant arthritis （AA） rats with wind-dampness-heat arthralgia by quantitative proteomics. MethodSixty SD rats were randomly divided into normal group， model group， angelica came pain soup low， medium and high dose group and methotrexate （MTX） group， each group of 10， only the rat tail root subcutaneously inactivated mycobacterium tuberculosis （Mtb） of adjuvant to build model of AA， artificial climate box intervention 16 d rheumatic fever bi syndrome model is set up， building the day began to drug intervention， The intervention lasted for 28 days. The proteins of synovial tissues in experimental rats were extracted. The differential proteins in the medium-dose DGNT group and the model group were detected and analyzed by 4D label-free quantification （4D-LFQ） proteomics. The differentially expressed proteins associated with mitochondrial pathway apoptosis were verified by immunohistochemistry and Western blot. ResultA total of 4 756 proteins were identified from rat synovial tissues， of which 4 234 proteins contained quantitative information. There were 814 differential proteins between the model group and the DGNT group. As revealed by Gene Ontology （GO） and Kyoto Encyclopedia of Gene and Genome （KEGG） enrichment analyses， DGNT had an effect on the synovial proteome of AA rats with wind-dampness-heat arthralgia， and the differential proteins were enriched in the regulation of the immune system， response to acute inflammation， and apoptosis regulation. As demonstrated by the results of immunohistochemistry and Western blot， compared with the model group， the DGNT groups and the MTX group showed increased protein expression of B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax） and cytochrome C （Cyt C）（P<0.05， P<0.01）， reduced Bcl-2 level （P<0.05， P<0.01）， elevated level of cleaved cysteinyl aspartate-specific protease 9 （Caspase-9）/Caspase-9 （P<0.01）， and decreased level of phosphorylated protein kinase B （p-Akt）/Akt（P<0.05， P<0.01）. ConclusionDGNT involved multiple targets in the treatment of AA with wind-dampness-heat arthralgia and it may exert its effect in the prevention and treatment by regulating the Akt/Bax/Bcl-2 pathway and promoting the cell apoptosis in the mitochondrial pathway.

Characteristics and Functional Differences of Intestinal Flora in Type 2 Diabetes Mellitus Patients with Dampness Heat Trapping Spleen Syndrome and Qi-Yin Deficiency Syndrome： An Analysis Based on High-throughput Sequencing Technology / 中国实验方剂学杂志

ObjectiveTo explore the structural characteristics and functional differences of intestinal flora in patients with type 2 diabetes mellitus （T2DM） of dampness heat trapping spleen（DHTS） syndrome and Qi-Yin deficiency（QYD） syndrome. MethodFrom June 2018 to January 2020，62 T2DM patients with DHTS syndrome and 60 with QYD syndrome were selected from Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Serum and fecal samples were collected to compare body mass index（BMI），glucose and lipid metabolism，fasting insulin （FINS） and fasting C-peptide （FCP） levels，and homeostasis model assessment of insulin resistance（HOMA-IR） of the two syndrome types. Fecal samples were extracted for DNA database construction，and 16S rDNA high-throughput sequencing was used to analyze and compare the intestinal flora and metabolic pathways. Result① The BMI，fasting plasma glucose（FPG），2-hour postprandial blood glucose （2 h PBG），total cholesterol（TC），triglyceride（TG），low density lipoprotein（LDL），FINS，FCP，and HOMA-IR were higher in patients with DHTS syndrome than in patients with QYD syndrome，and the high density lipoprotein（HDL） of the former was lower than that of the latter，（P<0.05，P<0.01）. ② In terms of species composition and differences，Bacteroidetes， Clostridia and Gammaproteobacteria were dominant at the class level，and the relative abundance of Clostridia，Mollicutes and Verrucomicrobiae in QYD syndrome group was higher than that in DHTS syndrome group. At the order level，Bacteroidales，Clostridiales and Enterobacteriales were mainly found. The relative abundance of Clostridiales，Erysipelotrichales and Verrucomicrobiales in QYD syndrome group was obviously higher than that in DHTS syndrome group，while Aeromonadales in the former was lower than that in the latter （P<0.05）. At the family level，Bacteroidaceae，Prevotellaceae and Ruminococcaceae were predominant. The relative abundance of Ruminococcaceae，Porphyromonadaceae and Erysipelotrichaceae in QYD syndrome group was higher than that in DHTS syndrome group（P<0.05）. At the genus level，Bacteroides，Prevotella and Parabacteroides were mainly found. The relative abundance of Parabacteroides，Butyrivibrio and Ruminiclostridium in QYD syndrome group was higher than that in DHTS syndrome group，while that of Klebsiella and Megasphaera in DHTS syndrome group was higher than that in QYD syndrome group（P<0.05）. ③ Through Venn analysis of operational taxonomic units（OTU），it was found that there were 49 OTUs in patients with DHTS syndrome patients and 47 OTUs in QYD syndrome patients. ④ The results of OTU β diversity and α analysis showed that Shannon and Simpson indexes had statistical differences，while Ace and Chao indexes had no statistical differences. The intestinal microbial diversity of patients with QYD syndrome was higher than that of patients with DHTS syndrome（P<0.05）. The analysis of similarities （ANOSIM） showed that the difference of β diversity between the two groups was significant（P<0.05）. ⑤ Linear discriminant analysis Effect Size（LEfSe） results demonstrated that Klebsiella，Megasphaera and Aeromonadales could be selected as the key biomarkers for DHTS syndrome； 14 bacteria such as Ruminiclostridium，Burkholderiaceae，Lautropia，Butyrivibrio，Erysipelotrichales can be selected as the key biomarkers for QYD syndrome. ⑥Functional annotation and analysis showed that the DHTS syndrome involved 9 metabolic pathways，including arginine and proline metabolism，lipopolysaccharide biosynthesis，nicotinic acid and nicotinamide metabolism，while the QYD syndrome involved 10 metabolic pathways，including acarbose and valinomycin biosynthesis，glucagon signaling pathway and NOD-like receptor signaling pathway. ConclusionThere are obvious differences in intestinal flora and functions in T2DM patients of DHTS syndrome and QYD syndrome，which can be used as reference for traditional Chinese medicine （TCM） syndrome differentiation and the target of TCM treatment.

Effect of Shaoyaotang on Inflammatory Cytokines and Intestinal Flora in Rats with Dampness-heat Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shaoyaotang on diarrhea， inflammation， and intestinal flora in rats with dampness-heat diarrhea and explore the mechanism of therapeutic principle "treating incontinent syndrome with dredging method" of Shaoyaotang. MethodThe dampness-heat diarrhea model was induced by high temperature， high humidity， high sugar and fat diet， and pathogenic factors. The rats were divided into normal group， model group （normal saline）， Shaoyaotang group （5.62 g·kg-1）， Rhei Radix et Rhizoma （RRER）-free Shaoyaotang group （5.15 g·kg-1）， and RRER group （0.01 g·kg-1）. The rats were treated correspondingly for five days， twice a day in the morning and evening. The diarrhea index was used to evaluate the antidiarrheal effect of each group three hours after the administration in the evening. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-2， and IL-6 in the serum were detected by enzyme-linked immunosorbent assay （ELISA） three hours after the last administration. The structure of intestinal flora in feces was characterized by 16sDNA. ResultCompared with the model group， the Shaoyaotang group， the RRER-free Shaoyaotang group， and the RRER group showed reduced diarrhea index （P<0.01）， with the onset rates ranking as the Shaoyaotang group>the RRER-free Shaoyaotang group>the RRER group. Those three groups with drug intervention all showed decreased levels of inflammatory factors （P<0.01）， especially the Shaoyaotang group， and no significant difference was observed between the RRER group and the RRER-free Shaoyaotang group. The abundance of pathogenic bacteria and conditioned pathogens （e.g. Escherichia-Shigella， Prevotella， Enterorhabdus， and Bacteroides） was reduced and the proliferation of probiotics （such as Ruminococcus， Turicibacter， and Lachnospiraceae） was increased in the groups with drug intervention （P<0.01）. For the structure of intestinal flora， the RRER group and the Shaoyaotang group were close to the normal group， and the RRER-free Shaoyaotang group was different from the other three groups （P<0.01）. ConclusionShaoyaotang can improve the outcome of rats with dampness-heat diarrhea through anti-inflammation and regulation of intestinal flora disorders. RRER in the prescription plays a key role in reducing the abundance of harmful bacteria and promoting the proliferation of probiotics， which is the key of Shaoyaotang in promoting the re-balance of intestinal flora. It also confirms the scientificity of treating dampness-heat diarrhea with RRER following the therapeutic principle "treating incontinent syndrome with dredging method".

Property-efficacy Relationship of Scutellariae Radix and Atractylodis Rhizoma in Drying Dampness in Rats with Spleen-stomach Dampness-heat Syndrome / 中国实验方剂学杂志

Objective:To observe the difference in drying dampness between Scutellariae Radix and Atractylodis Rhizoma in model rats with spleen-stomach dampness-heat syndrome and clarify their property-efficacy relationship. Method:Sixty-four healthy male SD rats were randomized into the blank group， model group， high-， medium-， and low-dose Scutellariae Radix groups， as well as high-， medium-， and low-dose Atractylodis Rhizoma groups. The rats were exposed to high-fat and high-sugar diet and external dampness-heat environment for 20 days for inducing the spleen-stomach dampness-heat syndrome. The macroscopic manifestations of rats were observed and the morphological changes in stomach and colon were detected under a light microscope after hematoxylin-eosin （HE） staining， followed by the calculation of pathological scores. The serum tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-4 （IL-4）， and interferon-<italic>γ</italic> （IFN-<italic>γ</italic>） levels were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of aquaporin-4 （AQP4） in the gastric tissue were measured by Western blot and Real-time polymerase chain reaction （Real-time PCR）， respectively. Result:Rats in the model group presented with the manifestations of dampness-heat syndrome. The inflammatory reaction in stomach and colon was obvious， and the pathological score was significantly increased （<italic>P</italic><0.01）. The serum IFN-<italic>γ</italic>， IL-4， and TNF-<italic>α</italic> levels were elevated （<italic>P</italic><0.05）， and so were the AQP4 protein and mRNA expression levels in the gastric tissue except that there was no statistical difference. The clinical symptoms of rats in the medication groups were alleviated. Scutellariae Radix significantly relieved the gastric and colonic inflammation in model rats. Atractylodis Rhizoma inhibited the colonic inflammation in model rats to a certain extent， but it had no obvious effect on gastric inflammation. The pathological score of each Scutellariae Radix group was decreased. In terms of the pathological score of gastric tissue， only the high-dose Scutellariae Radix produced a significant difference （<italic>P</italic><0.01）， and the pathological scores of the three Atractylodis Rhizoma groups were not significantly different from that in the model group. As for the pathological score of colonic tissue， all the medication groups except for the low-dose Atractylodis Rhizoma group exhibited a significant difference in comparison with that of the model group （<italic>P</italic><0.01）. Scutellariae Radix and Atractylodis Rhizoma at each dose reduced not only the serum IFN-<italic>γ</italic>， IL-4， and TNF-<italic>α</italic> levels （<italic>P</italic><0.05， <italic>P</italic><0.01）， but also the AQP4 protein expression in gastric tissue of model rats （<italic>P</italic><0.01）. The AQP4 mRNA expression in the gastric tissue of model rats declined in the high- and low-dose Scutellariae Radix groups， while that in the medium-dose Scutellariae Radix group and each Atractylodis Rhizoma group rose without statistical difference. Conclusion:Scutellariae Radix and Atractylodis Rhizoma display a certain property-efficacy relationship in drying dampness of rats with spleen-stomach dampness-heat syndrome. Specifically， the efficacy of drying dampness is related to their cold/heat property， and the resulting outcome of bitter-cold Scutellariae Radix is better than that of bitter-warm Atractylodis Rhizoma.

Clinical Study of Modified Chushi Juanbitang Combined with Pedicle Vertebrotomy on Kyphosis of Ankylosing Spondylitis Due to Syndrome of Dampness-heat Obstruction / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Chushi Juanbitang combined with pedicle vertebrotomy on kyphosis of ankylosing spondylitis due to syndrome of dampness-heat obstruction. Method:The 90 cases were randomly divided into control group and observation group， 45 cases in each group. The patients in control group received pedicle vertebrotomy + <italic>Tripterygium</italic> glycosides， and the patients in observation group received pedicle vertebrotomy + modified Chushi Juanbitang. The treatment course was 6 months in both groups. Their bath ankylosing spondylitis disease activity index （BASDAI）， bath ankylosing spondylitis measure index （BASMI）， imaging index， traditional Chinese medicine syndromes， serum proinflammatory factor， anti-inflammatory factor， bone metabolism index ［bone-specific alkaline phosphatase （BALP）， tartrate resistant acid phosphatase isomer-5b （TRACP-5 b）， bone morphogenetic protein-2 （BMP-2）， osteocalcin （BGP）］， ossification related proteins ［bone morphogenetic protein-7 （BMP-7）， dickkopf-related protein-1 （DKK-1）， and tissue inhibitor matrix metalloproteinase-2 （TIMP-2）， sclerostin（SOST）］ were observed and detected. The clinical efficacy， recurrence rate and safety indexes were followed up for 12 months and compared. Result:The total effective rate was 97.73% （43/44） in the observation group， higher than 80.95% （34/42） in the control group （<italic>χ</italic>²=5.172， <italic>P</italic><0.05）. In the comparison with control group after treatment， the BASDAI， BASMI， imaging index， traditional Chinese medicine syndromes， proinflammatory factors， TRACP-5b， BMP-7 and TIMP-2 were lower in observation group （<italic>P</italic><0.05）， and the anti-inflammatory factors， BALP， BMP-2， BGP， DKK-1 and SOST were higher in observation group （<italic>P</italic><0.05）. During the follow-up for at least 12 months， the recurrence rate was 4.65% （2/43） in observation group， lower than 26.47% （9/34） in control group （<italic>χ</italic>²=4.261， <italic>P</italic><0.05）. There was no significant difference in the incidence of postoperative complications between the two groups. The incidence of adverse reactions was 2.27% （1/44） in observation group， lower than 38.64% （17/44） in control group （<italic>χ</italic>²=5.763， <italic>P</italic><0.05）. Conclusion:Modified Chushi Juanbitang combined with pedicle vertebrotomy is effective in the treatment of kyphosis of ankylosing spondylitis due to syndrome of dampness-heat obstruction.

Modified Qiaohetang and Xiehuangsan in Treatment of Acne Due to Dampness-heat Accumulation / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Qiaohetang and Xiehuangsan in the treatment of acne due to dampness-heat accumulation and its influence on the levels of inflammatory factors and sex hormones. Method:One hundred and sixty-eight eligible patients were divided into an observation group （84 cases） and a control group （84 cases） according to the random number table. Adapalene gel was applied externally in both groups， one time per day. In the control group， Jinhua Xiaocuo pills was taken orally， 4 g per time， three times a day. In the observation group， the modified Qiaohetang and Xiehuangsan was provided for oral administration， one bag per day. The treatment lasted for eight weeks. The Global Acne Grading System （GAGS） score， skin lesion count， dampness-heat accumulation syndrome score， and Dermatology Life Quality Index （DLQI） score were recorded before and after treatment， followed by the detection of interleukin-8 （IL-8）， IL-10， IL-17， interferon-<italic>γ</italic> （IFN-<italic>γ</italic>）， free testosterone （FT）， estradiol （E₂） and sex hormone binding globulin （SHBG） before and after treatment as well as the safety evaluation. Result:The GAGS， dampness-heat accumulation syndrome， and DLQI scores of the observation group were lower than those of the control group （<italic>P</italic><0.01）. The counts of inflammatory skin lesions （papule and pustule）， non-inflammatory skin lesions， and total skin lesions in the observation group declined in contrast to those in the control group （<italic>P</italic><0.01）. The IL-8， IL-17， IFN-<italic>γ</italic> and FT levels of the observation group were decreased as compared with those of the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the IL-10， E₂， and SHBG levels were increased （<italic>P</italic><0.01）. The overall response rate in clinical symptom alleviation of the observation group was 93.67%（74/79）， which was higher than 81.82%（63/77） of the control group （<italic>χ</italic>²=5.121， <italic>P</italic><0.05）. The overall response rate in dampness-heat accumulation syndrome relief of the observation group was 92.41% （73/79）， still higher than 79.22% （61/77） of the control group （<italic>χ</italic>²=5.595， <italic>P</italic><0.05）. No adverse reactions occurred after the oral administration of Chinese medicinal preparations. Conclusion:The modified Qiaohetang and Xiehuangsan combined with adapalene gel can reduce the skin lesion count and severity， relieve both clinical symptoms and dampness-heat accumulation syndrome， regulate the inflammatory response and sex hormones， and improve the quality of life of patients with acne of dampness-heat accumulation syndrome without inducing side effects.

A Case Report of Chronic Idiopathic Urticaria Successfully Treated with Kampo Formula, Seijobofuto and Inchingoreisan / 日本東洋医学雑誌

We report a case of a 51-year-old male who suffered from chronic idiopathic urticaria on every part of his body. Urticaria appeared especially in the morning and evening. He visited our Kampo clinic because of insufficient effect of antihistamine drug and tokiinshi that had been prescribed by a dermatologist for about a half year. We thought this might be caused by blood deficiency, blood stasis and liver qi depression because he had symptoms of sensitiveness of heat, dry skin, purple tongue with yellow fur, a deeply located string-like pulse,and fullness in the chest and hypochondrium. Therefore, we administered keigairengyoto and ryutanshakanto but the effect was insufficient. During this treatment, we revealed his state of having thick fur in tonguediagnosis. Finally we prescribed him seijobofuto and inchingoreisan because we concluded that it might be necessary to remove dampness-heat in this case. His symptom improved within about a week after taking this formulation. Some cases of chronic urticaria are resistant to standard treatments in modern western medicine. Kampo medicine may be useful and hopeful in these cases.