Lianweng Granules Alleviate Intestinal Barrier Damage via the IL-6/STAT3/PI3K/AKT Signaling Pathway with Dampness-Heat Syndrome Diarrhea.

Dampness-heat syndrome diarrhea (DHSD) is a common clinical disease with a high prevalence but still has no satisfactory therapeutic medicine, so the search for a safe and effective drug candidate is ongoing. This study aims to explore the efficacy and mechanisms of Lianweng granules (LWG) in the treatment of DHSD and to identify the blood transport components of LWG. We assessed the efficacy of LWG in DHSD by various in vivo metrics such as body weight, disease activity index (DAI), histopathologic examination, intestinal barrier function, levels of inflammatory, apoptotic biomarkers, and oxidative stress. We identified the blood components of LWG using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS), and the resolved key components were used to explore the relevant targets. We next predicted the potential mechanisms of LWG in treating DHSD using network pharmacology and molecular docking based on the relevant targets. Finally, the mechanisms were validated in vivo using RT-qPCR, Western blotting, ELISA, and immunofluorescence and evaluated in vitro using Cell Counting Kit-8 (CCK-8), small interfering RNA, cellular enthusiasm transfer assay (CETSA), and drug affinity response target stability (DARTS). Ninety-one pharmacodynamic components of LWG enter the bloodstream and exert possible therapeutic effects. In vivo, LWG treatment improved body weight, reduced colonic injury and DAI scores, lowered inflammation, oxidative stress, and apoptosis markers, and partially restored intestinal barrier function in DHSD mice. Guided by network pharmacology and molecular docking, it is suggested that LWG may exert therapeutic effects by inhibiting IL-6/STAT3/PI3K/AKT signaling. LWG significantly decreased the expression of IL-6, p-STAT3, p-PI3K, p-AKT, and other proteins. These findings were supported by in vitro experiments, where CETSA, DARTS, and siRNA evidenced LWG's targeting of STAT3. LWG targeted STAT3 to inhibit inflammation, oxidative stress, and apoptosis in the colon, thereby restoring the intestinal barrier function to some extent and exerting a therapeutic effect on DHSD.

Observation of the efficacy of elongated needle therapy in treating patients with â ¢B prostatitis of stagnant dampness-heat syndrome. / 芒针治疗湿热瘀阻证⠢Båž‹å‰åˆ—è ºç‚Žæ‚£è€ çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To observe the clinical efficacy in patients with ⅢB prostatitis of stagnant dampness-heat syndrome treated with elongated needle therapy. METHODS: A total of 90 patients with ⅢB prostatitis of stagnant dampness-heat syndrome were selected and randomly divided into a treatment group(45 cases, 2 dropped out) and a control group(45 cases, 1 dropped out) using a random number table method. The control group was treated with oral administration of Qianlie Shutong Capsule, 3 capsules per dose, 3 times a day for a total of 4 weeks. The treatment group received elongated needle therapy at Qihai(CV6), Zhongji(CV3), bilateral Zhibian(BL54) and Shuidao(ST28), with one treatment per day for 4 weeks. Before and after treatment, the traditional Chinese medicine syndrome score, National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score were compared between the two groups, and the clinical efficacy was compared after treatment. RESULTS: Compared with that before treatment, the control group showed significant decrease in traditional Chinese medicine syndrome score, testicular pain, urinary frequency, unending remnants of urine, scrotal wetness, yellowish urine, urinary symptoms, and quality of life scores after treatment(P<0.05)；the treatment group showed significant decrease in traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain, scrotal wetness, yellowish urine scores, NIH-CPSI total score, pain symptoms, urinary symptoms, and quality of life scores after treatment(P<0.05). After treatment, the treatment group showed significantly lower traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain scores, NIH-CPSI total score, pain symptoms, and quality of life scores than those of the control group(P<0.05). The effective rate in the treatment group (63.64%, 28/43) was significantly higher than that in the control group (88.37%, 38/44, P<0.05). CONCLUSIONS: Elongated needle therapy can significantly improve the traditional Chinese medicine syndrome score, NIH-CPSI total score, and pain symptom scores in patients with ⅢB prostatitis of stagnant dampness-heat syndrome. It can significantly improve the cure rate in these patients and is particularly effective in relieving pain.

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.

[Correlation of traditional Chinese medicine to reduced re-admission risk in ankylosing spondylitis patients with dampness-heat syndrome: a retrospective cohort study].

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.

Yujin powder improves large intestine dampness-heat syndrome by regulating gut microbiota and serum metabolism.

Large intestine dampness-heat syndrome (LIDHS) is a common syndrome type in animal diarrheal diseases. Yujin powder (YJP) is one of the classic prescriptions for treating damp-heat diarrhea. The aim of this study was to investigate the regulatory effects of YJP on gut microbiota and serum metabolism in LIDHS rats using 16S rRNA sequencing and nontargeted metabolomics. The LIDHS rat model was induced through a high-sugar and high-fat diet, exposure to a high-temperature and high-humidity environment, and infection with Escherichia coli. The results demonstrated that the administration of YJP resulted in a decrease in the abundance of Desulfovibrio, Parabacteroides, Bacteroides, Allobaculum, Escherichia, Butyricimonas, Parasutterella, and Blautia and an increase in Ruminococcus, Akkermansia, Roseburia, and Lachnoclostridium. A total of 25 potential biomarkers were identified in three groups of rats. These metabolites were primarily involved in glycerophospholipid metabolism, taurine and hypotaurine metabolism, glycerol ester metabolism, arachidonic acid metabolism, primary bile acid synthesis, and tryptophan metabolism. Our study demonstrated that YJP has the potential to alleviate LIDHS by modulating gut microbial and serum metabolic homeostasis. These results establish a foundation and offer valuable guidance for the utilization of YJP in the treatment of LIDHS.

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.

Application of herbs and active ingredients ameliorate non-alcoholic fatty liver disease under the guidance of traditional Chinese medicine.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem, and its prevalence has been on the rise in recent years. Traditional Chinese Medicine (TCM) contains a wealth of therapeutic resources and has been in use for thousands of years regarding the prevention of liver disease and has been shown to be effective in the treatment of NAFLD in China. but the molecular mechanisms behind it have not been elucidated. In this article, we have updated and summarized the research and evidence concerning herbs and their active ingredients for the treatment in vivo and vitro models of NAFLD or NASH, by searching PubMed, Web of Science and SciFinder databases. In particular, we have found that most of the herbs and active ingredients reported so far have the effect of clearing heat and dispelling dampness, which is consistent with the concept of dampness-heat syndrome, in TCM theory. we have attempted to establish the TCM theory and modern pharmacological mechanisms links between herbs and monomers according to their TCM efficacy, experiment models, targets of modulation and amelioration of NAFLD pathology. Thus, we provide ideas and perspectives for further exploration of the pathogenesis of NAFLD and herbal therapy, helping to further the scientific connotation of TCM theories and promote the modernization of TCM.

Pathological mechanism of intestinal mucosal barrier injury of large intestine dampness-heat syndrome rats and the protective effect of Yujin powder.

Large intestine dampness-heat syndrome (LIDHS) is frequently-occurring in the inflammatory intestinal disease of animals and human. Yujin powder (YJP) is a classical prescription for treating LIDHS. To explore the pathological mechanism of intestinal mucosal barrier injury of LIDHS and the protection of YJP, the LIDHS rat model was established through imitating the inducing conditions of LIDHS and treated with YJP. The integrity of ileal and colonic mucosa was detected through histopathological examination. The serum DAO, D-LA and ET levels were detected by ELISA. The mRNA and protein expression levels of Occludin, ZO-1 and MUC2 in ileum and colon were detected using RT-PCR and immunohistochemistry methods, respectively. The results showed that the ileal and colonic epithelium of LIDHS rats were destroyed; the serum DAO, D-LA and ET levels were significantly increased; the mRNA and protein expression levels of Occludin, ZO-1 and MUC2 in ileum and colon were all abnormally expressed. After treatment with YJP, the mucosal integrity was restored; the levels of serum DAO, D-LA and ET, mRNA and protein levels of Occludin and ZO-1 in ileum and colon and MUC2 in ileum were back-regulated; however, MUC2 level in colon was further increased. The results demonstrated that the intestinal mucosal barrier was damaged in LIDHS rats and Occludin, ZO-1 and MUC2 were abnormally expressed, and YJP could repair the intestinal mucosal barrier through up-regulating the expression of Occludin and ZO-1 in ileum and colon as well as MUC2 in colon and down-regulating MUC2 in ileum.

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.

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.

Comparative serum microRNA array analysis of the spleen-stomach dampness-heat syndrome in different diseases: Chronic hepatitis B and chronic gastritis.

Spleen-stomach dampness-heat syndrome (SSDHS) is the common Traditional Chinese Medicine (TCM) syndrome observed in both chronic hepatitis B (CHB) and chronic gastritis (CG). The specialized TCM prescription for CHB and CG patients with SSDHS is same, but there is limited information about the biological characteristics of this TCM syndrome. This study aimed to identify the serum miRNAs profile for the SSDHS in two different diseases in order to evaluate the miRNA-mediated biological characteristics of this TCM syndrome. We performed comparative microarray analysis of serum miRNA expression profiles in 10 CHB patients with SSDHS (SSDHS-CHB), 10 CG patients with SSDHS (SSDHS-CG), and 10 healthy controls (HC). The selected miRNAs were further validated by qRT-PCR in 13 SSDHS-CHB patients, 13 SSDHS-CG patients, and 13 HC. Moreover, bioinformatics analysis (GO and KEGG pathway enrichment analyses) was applied to identify the involved target genes and pathways for these selected miRNAs. Nine significantly differentially expressed (SDE)-miRNAs in the SSDHS-CHB group and 24 SDE-miRNAs in the SSDHS-CG group were identified, compared with the HC group (fold change >2.0 and p < .05). Among these, upregulated hsa-miR-483-3p and downregulated hsa-miR-223-3p were identified as the common SDE-miRNAs for both SSDHS-CHB and SSDHS-CG groups. Bioinformatics analysis of the common SDE-miRNA's target genes showed their involvement in the regulation of inflammation, immune response, and tumorigenesis. SSDHS-specific hsa-miR-483-3p and hsa-miR-223-3p identified in this study indicated a relevance to the underlying biological basis of SSDHS, and may provide scientific basis for the application of same TCM prescription in CHB and CG.

Mechanism and Basis of Traditional Chinese Medicine Against Obesity: Prevention and Treatment Strategies.

In the last few decades, the incidences of obesity and related metabolic disorders worldwide have increased dramatically. Major pathophysiology of obesity is termed "lipotoxicity" in modern western medicine (MWM) or "dampness-heat" in traditional Chinese medicine (TCM). "Dampness-heat" is a very common and critically important syndrome to guild clinical treatment in TCM. However, the pathogenesis of obesity in TCM is not fully clarified, especially by MWM theories compared to TCM. In this review, the mechanism underlying the action of TCM in the treatment of obesity and related metabolic disorders was thoroughly discussed, and prevention and treatment strategies were proposed accordingly. Hypoxia and inflammation caused by lipotoxicity exist in obesity and are key pathophysiological characteristics of "dampness-heat" syndrome in TCM. "Dampness-heat" is prevalent in chronic low-grade systemic inflammation, prone to insulin resistance (IR), and causes variant metabolic disorders. In particular, the MWM theories of hypoxia and inflammation were applied to explain the "dampness-heat" syndrome of TCM, and we summarized and proposed the pathological path of obesity: lipotoxicity, hypoxia or chronic low-grade inflammation, IR, and metabolic disorders. This provides significant enrichment to the scientific connotation of TCM theories and promotes the modernization of TCM.

Effect of Gegenqinlian decoction on intestinal mucosal flora in mice with diarrhea induced by high temperature and humidity treatment.

The objective of this study is to investigate the regulation effects of the active ingredients in Gegenqinlian Decoction (GD) on the intestinal mucosal flora of mice with diarrhea induced by high temperature and humidity based on systems pharmacology approach. Fifteen mice were randomly assigned to three equal groups of five mice, namely control (ctcm) group, model (ctmm) group and treatment (cttm) group. Mice in the cttm group were given 20 mL/kg of GD and sterile water was used as a placebo control twice a day for four consecutive days. We used the third-generation molecular high-throughput sequencing technology to measure the intestinal mucosal flora changes in mice. Combined with network pharmacology to predict the medicinal substances and action targets of GD against diarrhea. Results showed that Operational Taxonomic Unit (OTU) number and Alpha diversity in the intestinal mucosal flora of cttm group recovered and higher than that of the ctcm group. There were differences in the community structure between the ctmm and cttm groups in the Principal Coordinates Analysis (PCoA). The relative abundance results indicated dominant bacteria species (such as Lactobacillus crispatus, Muribaculum intestinal, Neisseria mucosa) in the intestinal mucosa of the three groups. Moreover, we screened out 146 active ingredients in GD corresponding to 252 component targets, and 328 disease targets in diarrhea to obtain 31 drug-disease common targets. Protein-protein interaction (PPI) networks mainly involved the core proteins such as Tumor necrosis factor (TNF) and Interleukin-6 (IL-6). Enrichment analyses showed that GD played a role in the treatment of diarrhea by regulating the hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF) and adipocytokine signaling pathways and so on. In brief, the active ingredients of GD could intervene from oxidative stress and inflammatory response through multiple targets and multiple channels to adjust the balance of intestinal mucosa flora, thereby playing a role in the treatment of diarrhea. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-020-02628-0.

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.

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.

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.

Treatment effects and mechanisms of Yujin Powder on rat model of large intestine dampness-heat syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Yujin Powder (YJP), an old prescription, is one of the most classical prescription for treating the large intestine dampness-heat syndrome (LIDHS). However, its potential modern pharmacological mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to explore the essence of LIDHS and treatment mechanisms of the YJP on the LIDHS. METHODS: The rat model of LIDHS was established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment (HTHE), drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of LIDHS. Then the clinical symptoms and signs, blood routine, blood biochemistry, whole blood viscosity (WBV), serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed, respectively. RESULTS: The results showed that the clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of LIDHS, moreover, there were obvious systemic inflammatory response and extensive congestion. And after treatment with YJP in different dosages, the clinical symptoms and signs of the rats with LIDHS were improved; the indexes of blood routine and blood biochemistry and inflammatory cytokines levels tended to be normal; the WBV decreased and histopathological changes of major organs were alleviated or returned to normal. There was an obvious dose-effect relationship, and the high dose of YJP (HD-YJP) had the best treatment effects. CONCLUSIONS: These results suggested that in LIDHS, diarrhea was the major clinical manifestation; the large intestine was the main lesion area; mucosa injury, inflammation and congestion of the large intestine with systemic inflammatory response and congestion were the most typical pathological characteristics. Meanwhile, YJP exhibited the comprehensive effects of anti-diarrhea, anti-inflammation, lowering blood lipid, relieving blood stasis, repairing intestinal mucosa and regulation and protection of multiple organs on LIDHS. These findings provided not only important information for understanding the essence of LIDHS but also the theoretical basis for developing new-drugs for treating dampness-heat type of diarrheal diseases.

Haoqin Qingdan Decoction () 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 (, 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.