Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex， which is closely related to neurotransmitter regulation， oxidative stress response， inflammatory factors， neuroglial cell， and abnormal gene expression. Western medicine mainly uses phenobarbital， phenytoin sodium， carbamazepine， and other drugs， but long-term use also produces certain toxic and side effects. Traditional Chinese medicine （TCM） believes that the pathogenesis of epilepsy is related to wind， fire， phlegm， and blood stasis， which leads to dysfunction of viscera， disorder of Qi movement， and finally uncontrolled spirit. In recent years， TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug， Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm， awakening spirit and benefiting intelligence， and removing dampness and opening stomach， which has been widely used in clinic. In this paper， the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level， antioxidant stress response， scavenging oxygen free radicals， regulating the expression of c-fos gene， reducing the level of inflammatory mediators， resisting neuronal apoptosis， and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy， and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials （RCT） of traditional Chinese medicine （TCM） for treating chronic atrophic gastritis （CAG）， so as to provide references for constructing the core outcome set （COS） of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated， and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included， with a sample size of 44-398 cases. 164 outcome indicators were reported， with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes， followed by physical and chemical examination （69.41%）， TCM syndrome （12.69%）， symptoms and signs （11.15%）， safety indicators （5.37%）， quality of life （0.65%）， long-term prognosis （0.65%）， and economic evaluation （0.08%）. According to the statistical analysis， there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG， including various indicators， non-standard name reports， unclear primary and secondary indicators， random combination of subjective and objective indicators， neglected patient report outcome indicators， missing long-term prognosis and economic indicators， insufficient reporting of safety indicators， and inconsistent measurement tools and measurement time points. ConclusionIn the past five years， there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.

Objective:To investigate the mechanism of joint cavity injection of Dioscoreae Rhizoma polysaccharides （DRP） in protecting against cartilage degeneration and inhibiting the expression of inflammatory factors in the rabbit model of knee osteoarthritis to provide relevant references for the development and further research on DRP. Method:Fifty-five New Zealand white rabbits were selected for the induction of knee osteoarthritis model by the modified Hulth's modeling method. The model rabbits were randomly divided into a model group， a sodium hyaluronate group （1.00 mg·kg^-1）， and low- （0.7 mg·kg^-1）， medium- （1.43 mg·kg^-1）， and high-dose （2.15 mg·kg^-1） DRP group according to a random number table. One week after modeling， the rabbits in the groups with drug intervention were treated correspondingly for five weeks， once per week， and no intervention was performed in the model group. Five weeks later， the joint specimens were observed by visual observation. The articular cartilage tissues were observed under the light microscope for pathological sections and scores by hematoxylin-eosin （HE） staining and toluidine blue （TB） staining. The expression levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial fluid were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of matrix metalloproteinase-13 （MMP-13）， transforming growth factor-β₁ （TGF-β₁）， and type Ⅱ collagen （Col-Ⅱ） in the articular cartilage were measured by immunohistochemistry. Result:After five weeks of DRP intervention， compared with the model group， the DRP groups exhibited lowered levels of IL-6， IL-1β， and TNF-α in the synovial fluid （P<0.05）， reduced expression of MMP-13 in the articular cartilage （P<0.05）， and increased levels of TGF-β₁ and Col-Ⅱ （P<0.05）. Compared with the low-dose and high-dose DRP groups， the medium-dose DRP group showed reduced levels of IL-6， IL-1β， and TNF-α in the knee joint （P<0.05）， increased levels of TGF-β₁ and Col-Ⅱ in cartilage tissues （P<0.05）， and dwindled level of MMP-13 （P<0.05）. Compared with the sodium hyaluronate group， the medium-dose DRP group showed no significant differences in IL-6， IL-1β， and TNF-α in rabbit knee joints， and TGF-β₁， Col-Ⅱ， and MMP-13 in cartilage tissues. Conclusion:Joint cavity injection of DRP can significantly reduce the expression of IL-6， IL-1β， and TNF-α in rabbit synovial fluid， effectively inhibit the expression of MMP-13 in the articular cartilage to suppress the degradation of articular cartilage collagen and promote the synthesis of TGF-β₁ and Col-Ⅱ. Therefore， DRP can protect and repair articular cartilage to delay the degeneration of articular cartilage.

Diabetic cardiomyopathy occurs in diabetic patients and is different from hypertensive heart disease， coronary atherosclerotic heart disease， and other cardiac abnormalities. The main clinical symptoms are systolic and diastolic cardiac dysfunction， myocardial fibrosis， congestive heart failure， and angina pectoris. As one of the main complications of diabetes， its incidence and fatality rates have been on the rise year by year. However， modern medicine still fails to figure out its pathogenesis and no specific drug is available， which has seriously affected the survival and quality of life of patients. Cardiomyocytes contain a large number of mitochondria， which participate in cardiac energy metabolism and other biological activities and occupy an important position in the development of diabetic cardiomyopathy. Mitochondrial quality control mainly involves mitochondrial oxidative stress， mitochondrial dynamics， mitochondrial autophagy， and intracellular calcium regulation， which is an important condition for stabilizing the normal mitochondrial structure and exerting normal mitochondrial functions. In recent years， the efficacy of traditional Chinese medicine in intervening in mitochondrial quality control through multiple angles， pathways， and targets to affect the structure and function of myocardial mitochondria and significantly improve the clinical symptoms of patients with diabetic cardiomyopathy has attracted wide attention from scholars. Therefore， this paper reviewed the experimental studies and/or clinical observations concerning the treatment of diabetic cardiomyopathy with effective compounds of Chinese herbs and/or Chinese herbal compounds in the past ten years to further explain the pathogenesis of diabetic cardiomyopathy， clarify the regulatory mechanism of traditional Chinese medicine in mitochondrial quality control， and summarize the scientific connotations and shortcomings of traditional Chinese medicine in the treatment of diabetic cardiomyopathy， hoping to provide certain ideas and methods for further clinical application of traditional Chinese medicine in the treatment of diabetic cardiomyopathy.

To observe and evaluate the clinical efficacy of transcutaneous auricular vagus nerve stimulation instrument for sleep disorder at high altitude plateau. Methods The patients with high altitude sleep disorder in the group were randomly divided into control group （n=30）and observation group （n=27）. The observation group received percutaneous vagal stimulation，and the control group received pseudo stimulation intervention for two weeks，five times a week. Before and after treatment，the two groups were measured with Pittsburgh Sleep Quality Index （PSQI） and Beck Depression Inventory （BDI），Generalized Anxiety Disorder （GAD-7） were evaluated. Results There was no significant difference in PSQI，BDI-21 and GAD-7 scores between the two groups before treatment （P> 0.05）；After two weeks of treatment，the total scores of PSQI and BDI-21 in the observation group were lower than those in the control group （P< 0.01），and the improvement of PSQI and BDI-21 scores in the observation group was higher than that in the control group，but there was no significant difference in GAD-7 scores between the two groups before and after treatment（P> 0.05）. Conclusion Transcutaneous auricular vagus nerve stimulation can effectively improve the sleep quality of patients with high altitude sleep disorders and reduce the level of depression. However，the intervention cycle of this trial is short and there is a lack of polysomnography indicators. It is still necessary to carry out long-term，large sample and multi-index trials to provide basis for clinical promotion.

[Abstract] Objective:To investigate the anti-tumor effect and mechanism of new LL-37 hybrid peptide on breast cancer MCF-7 cells. Methods: Human antimicrobial peptide LL-37 and human neutrophil peptide 1(HNP-1) were screened by using of Antimicrobial Peptides Database (http:// aps.unmc.edu/AP/main.php). The new LL-37 hybrid peptide was synthesized by integrating the active fragments, which were selected by bioinformatics analysis. The breast cancer MCF-7 cells and human normal breast MCF10A cells were treated with the new LL-37 hybrid peptides (0~70 μmol/L). Cell viability was monitored by CCK-8 assay and the affinity of the new LL-37 hybrid peptide with MCF-7 cells was observed using confocal laser scanning microscope (CLSM). The effects of LL-37 and caspase inhibitor on apoptosis and cell cycle of MCF-7 cells were measured by FCM (flow cytometry). Results: The new LL-37 hybrid peptide, as an amphiphilic cationic polypeptide, could selectively inhibit the proliferation of breast cancer MCF-7 cells ( P <0.05) with an IC50of 58.34 μmol/L, but exerted no significant effect on normal breast MCF10A cells. LL-37 peptide had high affinity with MCF-7 cells, which could cause S-stage stagnation and significantly increased early apoptosis ( P <0.01); however, the cell cycle block and apoptosis were significantly attenuated after the treatment of caspase inhibitor ( P <0.01). Conclusion: The new LL-37 hybrid peptide has anti-tumor activity on breast cancer MCF-7 cells, and could induce MCF-7 cells apoptosis possibly by arresting cell cycle via the caspase-dependent signaling pathway.

Chronic kidney disease （CKD） has become a public health problem worldwide with renal interstitial fibrosis （RIF） serving as the important pathological feature and pathological outcome of various CKD. Therefore， anti-fibrosis therapy has important practical significance for delaying the progression of CKD and improving the prognosis of CKD patients. The Wnt/β-catenin signaling pathway is a conserved signaling pathway through evolution， which plays a vital role in organ formation， tissue homeostasis， and disease progression during embryonic development. A growing body of research has confirmed that the Wnt/β-catenin signaling pathway is one of the key signaling pathways in a variety of kidney diseases and its activation is closely related to RIF. RIF is aggravated by the specific regulation of the expression of downstream target genes， such as fibroblasts， zinc finger transcription factor 1 （Snail1）， M2 macrophages， matrix metalloproteinase-7 （MMP-7）， plasminogen activator inhibitor-1 （PAI-1）， and renin-angiotensin system（RAS）， and relieved by targeting the signaling pathways， such as Klotho， Dickkopf-related protein 1 （DKK1）， secreted frizzled-related protein 1 （Sfrp1）， and indocyanine green-001. In addition，the pathological view of RIF in traditional Chinese medicine （TCM） coincides with that in western medicine. Based on the etiology and pathogenesis of TCM in the combination of deficiency and excess， TCM regulates fibrosis-promoting mediators by tonifying deficiency， eliminating turbidity， removing the toxin， resolving stasis， and treating both symptoms and root causes in a multi-target， multi-layer， and multi-pathway manner to inhibit the Wnt/β-catenin signaling pathway and play an important role in renal protection. Therefore， this study reviewed the regulatory mechanism of the Wnt/β-catenin signaling pathway in RIF and the protective effect of targeting this signaling pathway on renal function and discussed the potential role of TCM in delaying the progression of RIF， which is expected to provide new targets and strategies for the prevention and treatment of RIF.

OBJECTIVE: To observe the impacts of electroacupuncture (EA) on neurological function, the pathological morphology in brain tissue, apoptosis level and the protein expressions of apoptosis-related cytochrome C (Cyt-C) and cysteine aspartic acid protease-9 (Caspase-9) in the rats with traumatic brain injury (TBI) and explore the potential mechanism of EA in treatment of TBI. METHODS: A total of 70 clean-grade SD mice were randomized into a blank group (8 rats), a sham-operation group (8 rats), a model group (27 rats) and an EA group (27 rats). In terms of interventions of 3, 7 and 14 days, 3 subgroups were divided in the model group and the EA group successively, 9 rats in each subgroup. The modified Feeney free-fall percussion method was adopted to establish TBI models of rats. In the sham-operation group, only the skull was exposed and drilled and no free-fall percussion was exerted. One day after modeling, EA was given in the rats of EA group at "Shuigou" (GV 26), "Baihui" (GV 20) and "Neiguan" (PC 6) and "Zusanli" (ST 36) on the affected side, with intermittent wave, 2 Hz in frequency, once daily, 10 min each time, for 3, 7 and 14 days successively. Separately, on the day 3, 7 and 14 of intervention, the modified neurological severity scale (mNSS) was used to evaluate the degree of neurological function injury in the rats, HE staining and Nissl staining were to observe the pathological and morphological changes in brain tissue, TUNEL method was to observe the level of apoptosis in brain tissue and immunohistochemistry (IHC) method and Western blot were to determine the protein expressions of Cyt-C and Caspase-9 in brain tissue. RESULTS: Compared with the sham-operation group, on the day 3, 7 and 14 of intervention, mNSS scores were increased obviously in the rats of the model group respectively (<0.01). Compared with the model group, on the day 3, 7 and 14 of intervention, mNSS scores were reduced in the rats of the EA group respectively (<0.05). On day 3 of intervention, in brain injury region of the rats in the model group and the EA group, gross tissue necrosis, nuclear fragmentation, consolidation and obvious vacuolar changes, reduced Nissl bodies and scattered arrangement were found. On day 7 and 14 of intervention, in the model group and the EA group, the new connective tissue filling and normal cells were visible and Nissl bodies increased. The overall repair and Nissl body quantity in the EA group were better than the model group. Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the numbers of apoptotic cells were increased obviously in the model group (<0.01) and they were reduced in the EA group as compared with the model group (<0.05). Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue were all increased obviously in the model group (<0.01) and they were all reduced in the EA group as compared with the model group successively (<0.05). CONCLUSION Electroacupuncture remarkably improves the condition in the neurological function injury and reduces apoptosis degree in TBI model rats, which is likely related to the down-regulation of the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue and further to bring the impacts on mitochondria mediated apoptosis process.
Animals ; Apoptosis ; Brain Injuries, Traumatic ; therapy ; Caspase 9 ; metabolism ; Cytochromes c ; metabolism ; Electroacupuncture ; Random Allocation ; Rats ; Rats, Sprague-Dawley

ObjectiveTo predict the mechanism of Sinitang in treating myocardial ischemia-reperfusion injury （MI/RI） based on network pharmacology and verify the prediction results by cellular experiments. MethodThe traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） was employed for retrieval of the main components and potential targets of Sinitang. Online Mendelian Inheritance in Man （OMIM） and GeneCards were employed to obtain the targets of Sinitang in treating MI/RI. STRING was employed to construct the protein-protein interaction （PPI） network， and DAVID to perform gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Finally， cellular experiments were carried out to verify the predicted anti-MI/RI mechanism of Sinitang. ResultA total of 105 active ingredients and 234 targets of Sinitang were screened out， among which 116 targets were predicted to be involved in the treatment of MI/RI. The GO annotation gave 587 entries， including 417 biological process entries， 101 cell component entries， and 69 molecular function entries. The KEGG analysis enriched 125 signaling pathways， involving vascular endothelial growth factor （VEGF）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， forkhead box transcription factor O （FoxO）， hypoxia-inducible factor-1 （HIF-1） apoptosis and other signaling pathways. The results of cell viability assay showed that Sinitang increased the survival rate of H9C2 cells damaged by hypoxia/reoxygenation （H/R）. Sinitang decreased the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and creatine kinase-MB （CK-MB） in H9C2 cells damaged by H/R. The results of flow cytometry demonstrated that Sinitang decreased the apoptosis rate of H9C2 cells damaged by H/R. Western blot showed that Sinitang down-regulated the expression of Bcl-2 related X protein （Bax） and up-regulated that of B-cell lymphoma-2 （Bcl-2） in H/R-injured H9C2 cells. ConclusionSinitang treats MI/RI in a multi-target and multi-pathway manner， which involves the signaling pathways associated with apoptosis.