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.

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.

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.

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.

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.

Ultrastructure Characteristics of Different Chinese Medicine Syndromes of Helicobacter pylori-Correlated Gastric Diseases / 中国结合医学杂志

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 dampness-heat 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's obviously different in ultrastructure of DHPW and PQD patients under TEM, which may give a helpful hint for the microcosmic syndrome differentiation of HPCG.

Sophora alopecuroides ameliorates large intestine dampness-heat syndrome in rats by serum metabolomic approach based on UHPLC-Q/TOF-MS/MS / 药学学报

The Chinese herbal Sophora alopecuroides is widely used to clean intestine and eliminate dampness, and it has good therapeutic effects on treating bacillary dysentery and inflammatory bowel disease, etc. in clinics. However, the mechanism of treatment is not yet well understood. The present study was aimed to explore the mechanism of Sophora alopecuroides treatment of large intestine dampness-heat syndrome (LIDHS). The LIDHS model was performed by the comprehensive factors, including high temperature and humidity environment, high-sugar and high-fat diet, and intraperitoneal injection of Escherichia coli. The blood routine, serum proinflammatory cytokine levels and histopathological changes of intestine were detected and observed. Meanwhile, the serum metabolomic approach was conducted using the method of ultra performance liquid chromatography coupled to quadrupole time-of-flight mass/mass spectrometry (UHPLC-Q/TOF-MS/MS). The results showed that Sophora alopecuroides has good therapeutic effects on the LIDHS rat models. After treatment with Sophora alopecuroides, the abnormality of blood routine indexes as well as proinflammatory cytokines, including IL-1β, IL-2, IL-6 and TNF-α in vivo, tended to be normal, and the histopathological changes of intestine were improved. Through metabolic profiling and protocol analysis, 9 potential metabolic markers may be closely related with the treatment mechanism of Sophora alopecuroides on this disease, including taurine, L-tryptophan, LysoPE, LysoPC, LPA, DG, chenodeoxycholic acid disulfate, traumatic acid and 7-ketodeoxycholic acid, which were involved in taurine and hypotaurine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, tryptophan metabolism and primary bile acid biosynthesis etc. The serum metabolomic approach can be applied to clarify the therapeutic mechanism of Sophora alopecuroides on LIDHS, and provide the theoretical basis for Sophora alopecuroides in clinical practice.

Haoqin Qingdan Decoction () and ribavirin therapy downregulate CD14 and toll-like receptor 4 in febrile disease with dampness-heat syndrome in a mouse model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Chinese medicine Haoqin Qingdan Decoction (, HQD) for febrile disease dampness-heat syndrome (FDDHS).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Relation between dampness-heat syndrome of acute period of GBS and neuroendocrine-immunoregulatory network / 中华中医药杂志

Objective: To discuss the relation between dampness-heat syndrome of GBS and neuroendocrine-immunoregulatory network.Methods: 34 patients with GBS were divided into dampness-heat syndrome group and nondampness-heat syndrome group by syndromes differentiation of TCM.The autonomic nerve function,the level of immunoglobulin,cortisol(COR) and adrenocorticotropin(ACTH) of these two groups were detected.The datas were compared with that of normal control group.Results:① There were significant difference in function of autonomic nerve between the two groups(damp-heat syndrome group and nondamp-heat syndrome group) and normal control group.There is difference between dampness-heat syndrome group and nondampness-heat syndrome group,too.Dampness-heat syndrome group mainly showed sympathetic nerve excitement(60.0%).In nondampness-heat syndrome group,the incidence of sympathetic nerve excitement is 35.7%;parasympathetic nerve excitement is 28.6%.② In dampness-heat syndrome group the level of IgG was higher than that in nondampness-heat syndrome group and normal control group.The level of IgA was higher than that in normal control group(P