Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Mechanism of polyphyllin A in inhibition of proliferation and induction of apoptosis of gastric cancer cells by directly targeting ETS-1 / 中国中药杂志

The present study investigated the mechanism of polyphyllin A(PPA) in inhibiting gastric cancer(GC) cells. GC cells(SGC7901 and MGC803 cell lines) were treated with PPA at different concentrations. The effect of PPA on the proliferation of GC cells was detected by MTT assay, real-time cell analysis(RTCA) assay, and clone-forming assay, respectively. Reactive oxygen species(ROS) of GC cells was detected by flow cytometry. The change of mitochondrial membrane potential was detected by JC-1 assay. The expression and phosphorylation levels of apoptosis-related proteins(caspase-9, caspase-3, and PARP) and proteins related to the signaling pathway(ETS-1, CIP2 A, and Akt) were detected by Western blot. The binding sites of PPA to ETS-1 were analyzed by molecular docking. The affinity of PPA and ETS-1 was detected by drug affinity responsive target stability(DARTS) assay. PPA had a significant inhibitory effect on the proliferation and colony formation of GC cells at a low concentration. The PPA groups showed increased ROS and decreased mitochondrial membrane potential. PPA down-regulated the precursor expression of caspase-9 and caspase-3 and promoted the cleavage of PARP, suggesting that PPA induced the apoptosis of GC cells through the mitochondrial pathway. PPA significantly reduced expression levels of CIP2 A and the phosphorylation of downstream Akt. Molecular docking showed that PPA bound to the ETS domain of ETS-1, the transcription factor of CIP2 A, and formed hydrogen bonds with Pro319 and Asp317. DARTS assay further confirmed that PPA significantly prevented the hydrolysis of ETS-1 by pronase, which was inductive of the direct binding effect of PPA and ETS-1. PPA inhibits the proliferation and induces the apoptosis of GC cells by directly targeting ETS-1 to down-regulate the ETS-1/CIP2 A/Akt signaling pathway.

Mechanism of polyphyllin Ⅰ targeting EGFR to affect proliferation and apoptosis of human breast cancer cells / 中国中药杂志

This study aims to investigate the molecular mechanism of polyphyllin Ⅰ(PPⅠ) inhibiting proliferation of human breast cancer cells. Human breast cancer BT474 and MDA-MB-436 cells were treated with different concentrations of PPⅠ, and then the effect of PPⅠ on cell proliferation was detected by MTT assay, trypan blue dye exclusion assay, real-time cell analysis, and clone forming assay, respectively. The apoptosis was detected by Annexin V-FITC/PI staining and then analyzed by flow cytometry. The change of mitochondrial membrane potential was detected by flow cytometry after fluorescent probe JC-1 staining. Western blot was used to detect protein expression and phosphorylation. Molecular docking was performed to detect the binding between PPⅠ and EGFR. The affinity between PPⅠ and EGFR was determined by drug affinity responsive target stability assay. The results indicated that PPⅠ inhibited the proliferation and colony formation of BT474 and MDA-MB-436 cells in a time-and concentration-dependent manner. The PPⅠ treatment group showed significantly increased apoptosis rate and significantly decreased mitochondrial membrane potential. PPⅠ down-regulated the expression of pro-caspase-3 protein, promoted the cleavage of PARP, and significantly reduced the phosphorylation levels of EGFR, Akt, and ERK. Molecular docking showed that PPⅠ bound to the extracellular domain of EGFR and formed hydrogen bond with Gln366 residue. Drug affinity responsive target stability assay confirmed that PPⅠ significantly prevented pronase from hydrolyzing EGFR, indicating that PPⅠ and EGFR have a direct binding effect. In conclusion, PPⅠ inhibited the proliferation and induced apoptosis of breast cancer cells by targeting EGFR to block its downstream signaling pathway. This study lays a foundation for the further development of PPⅠ-targeted drugs against breast cancer.

The Genome-Wide Changes in Expression Profile of CML T Cells After Up-regulation of TCRζ Chain Expression / 中国实验血液学杂志

OBJECTIVE@#To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ.@*METHODS@#The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3@*RESULTS@#A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated.@*CONCLUSION@#The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.

LncRNA MALAT1 aggravates oxygen-glucose deprivation/reoxygenation-induced neuronal endoplasmic reticulum stress and apoptosis via the miR-195a-5p/HMGA1 axis

BACKGROUND: This study aimed to investigate the potential role and molecular mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in cerebral ischemia/reperfusion injury. RESULTS: Using an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we determined that the expression of MALAT1 was significantly increased during OGD/R. MALAT1 knockdown reversed OGD/R-induced apoptosis and ER stress. Mechanistically, MALAT1 promoted OGD/R-induced neuronal injury through sponging miR-195a-5p to upregulating high mobility group AT-hook1 (HMGA1). CONCLUSIONS: Collectively, these data demonstrate the mechanism underlying the invovlvement of MALAT1 in cerebral ischemia/reperfusion injury, thus providing translational evidence that MALAT1 may serve as a novel biomarker and therapeutic target for ischemic stroke.

Theoretical and Clinical Evidences of Dispelling Wind and Eliminating Dampness Therapy for Allergic Rhinitis / 中国实验方剂学杂志

The pathological mechanism of allergic rhinitis (AR) involves hierarchically acute and chronic reactions among antigens, immunocytes, immunoglobulins and inflammatory factors. AR, which is characterized by heterogeneity, reacts differently to the current treatment on diverse individuals. Some patients receive unsatisfying clinical outcomes after the treatment. Chinese herbal medicine has become a frequent option to treat AR because it can improve clinical symptoms with excellent safety. The description of Biqiu in ancient Chinese medical literatures is very similar to the clinical manifestation of AR. The major pathogeneses of Biqiu included infection of wind-cold pathogens, deficiency and cold in the lung, and evil depression into heat and wind. Therefore, in modern traditional Chinese medicine （TCM）, Biqiu is considered as an integration of AR, allergic sinusitis and vasomotor rhinitis. According to the pathogenesis and clinical manifestations of Biqiu (including AR), this disease belongs to wind disease in TCM. But modern TCM focuses on deficiency of internal organs and ignores wind evil in syndrome differentiation, contrary to the fact that wind medicine is always used in treating AR. This even leads to an abnormal phenomenon that clinical studies attach little importance to syndrome differentiation. In this paper, we started from the phenomenon that wind medicine is always used in TCM for AR, considering TCM literatures and the study results of modern therapy for wind diseases, and put forward the ideas as follows: AR belongs to exogenous wind disease in TCM, and wind pathogen is the major pathogen, in clinical syndrome differentiation, we should attach more importance to wind evil, and dispelling wind and eliminating dampness is the key to treatment. Meanwhile, based on the fact that most of the classical prescriptions with good effectiveness for AR originated from Treatise on Febrile Disease, mainly including the wind medicines for treating exogenous diseases, it can be inferred that the wind-dispelling and itch-arresting effects of wind medicines are helpful to alleviate or block the allergic reaction of nasal mucus and achieve the goal of relieving itching and sneezing, and the wind-dispelling and dampness-eliminating effects are helpful to alleviate the edema of nasal mucus and achieve the goal of relieving running nose and nasal obstruction. In modern researches, it is also found that classical prescriptions which take wind medicine as a principle component and wind medicine used in AR treatment have good anti-inflammatory, anti-allergic and immune function adjusting effects. This indicates that dispelling wind and eliminating dampness and the wind medicine treatment under its instruction not only correspond to TCM theory, but also have modern science evidences.

Changes of Intestinal Microecology in Patients with Primary Sjogren's Syndrome after Therapy of Yangyin Yiqi Huoxue Recipe () / 中国结合医学杂志

OBJECTIVE@#To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (, YYHD).@*METHODS@#Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group.@*RESULTS@#The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P0.05).@*CONCLUSIONS@#There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.

Effect of Two Kinds of Kinesio Taping Methods on Shoulder Pain in Hemiplegic Patients with Stroke during Spasm Period / 中国康复理论与实践

Objective To observe the effect of two kinds of Kinesio taping methods on shoulder pain in hemiplegic patients with stroke during spasm period. Methods From October,2015 to September,2017,75 stroke hemiplegic patients with shoulder pain during spasm period were randomly divided into group A(n=25),group B(n=25)and control group(n=25).Three groups were given conventional treatment,and group A and group B received two kinds of Kinesio taping methods,respectively.Be-fore and four weeks after treatment,the shoulder pain was assessed with Visual Analogue Scale(VAS),the motor function of upper limb was assessed with Fugl-Meyer Assessment(FMA),and their activities of daily living was assessed with modified Barthel Index(MBI). Results After treatment, the score of VAS significantly decreased in all groups (P<0.001), and was lower in groups A and B than in the control group(P<0.05),especially in group A(P<0.01);the scores of FMA and MBI signifi-cantly increased(P<0.001),and was higher in groups A and B than in the control group(P<0.05),especially in group A(P<0.05). Conclusion Kinesio taping combined with rehabilitation training for the treatment of stroke patients following hemiple-gia during spasm period can relieve the shoulder pain and improve the motor function of upper limb and activi-ties of daily living.The curative effect varies with different taping methods.

TCM Understanding and Treatment Progress of Haze Cough / 中国中医药信息杂志

Haze cough is a disease of respiratory system which is caused by haze in recent years. It has gradually caused people's attention because of its wide population, the obvious characteristics of the disease, long duration and long-term harm to the human body. This article reviewed research progress in TCM understanding of haze, the characteristics of haze cough, etiology and pathogenesis of haze cough, TCM treatment for haze cough, and TCM nursing of haze cough, aiming to provide references for the clinical treatment of haze cough.

Prescription regularity of famous veteran traditional Chinese medicine Doctor Yu Guoyou for treating gastrointestinal failure based ondata mining / 中国中药杂志

Gastrointestinal failure is a kind of severe systemic inflammatory response, and often complicated with multiple organ dysfunction syndrome. Integrated traditional Chinese and Western medicine have a better curative effect in treating it. This study collected the famous veteran TCM physician Yu Guoyou's 175 prescriptions for treating 89 cases of gastrointestinal failure, calculated the frequency of traditional Chinese medicines and their categories, and analyzed the medication regularity with system clustering method, so as to summarize Yu's frequently used drugs and prescriptions. The results showed the top three most frequently used drugs aremagnolia bark, bitter orange, and rhubarb, which are components of Xiaochengqi decoction; Among the traditional Chinese medicines, medicines of tonifying deficiency, regulating qi, clearing heat, eliminating phlegm and dissipating dampness are most commonly used. Among the tonic medicines, those for tonifying Qi accounted for 2/3, which was the largest proportion; At the same time, some new prescriptions and new drug combinations were excavated and could be used as the reference for clinical medication. According to the findings, when differentiating syndromes of gastrointestinal failure, Yu regards the spleen and stomach Qi deficiency as the root cause and the heat toxin, blood stasis, Qi stagnation and dampness as the symptoms. In the treatment of gastrointestinal function failure, Yu gives priority to strengthening spleen, regulating Qi and purgation, prescribes medicines for dissolving blood stasis and detoxication, dissipating dampness, clearing heat and eliminating phlegm according to syndrome types. In other words, the treatment is based on syndrome differentiation, and the prescription is modified according to symptoms. In particular, Yu attaches importance to stomach-Qi recuperation and gastrointestinal function recovery in the process of treatment.

Screen potential CYP450 2E1 inhibitors from Chinese herbal medicine based on support vector regression and molecular docking method / 中国中药杂志

Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use.

Construction of Medical Ethics Education Practice System for Medical Students / 中国医学伦理学

In this paper , based on the analysis of the facing predicament of current situation of medical ethics education , the authors combined with the practice of medical ethics education and the school experience , based on the theory of life education , put forward to experience the activities of public medical treatment building practice of medical students medical ethics education system , promote the educational work to carry out the practice of medical colleges, improve the teaching quality of medical ethics education .

Combined external skeletal fixation instrumentation with locked intramedullary nailing for tibia lengthening / 中华外科杂志

<p><b>OBJECTIVE</b>To shorten the time of external skeletal fixation on legs, and enhance quality of limb lengthening, avoid complications of shortening, bending, twisting and etc.</p><p><b>METHODS</b>Insert pin transcortical to attack external skeletal fixation simultaneously, put un-reaming locked intramedullary nail (do not insert distal locked screw) into endosteum of lengthening bone. After the legs achieved predetermined length, insert distal locked screw and then remove external skeletal fixation, locked intramedullary nail, then maintain consolidation of rehabilitation.</p><p><b>RESULTS</b>The group lengthened legs for 412 cases. The range of lengthening was 3 to 18 cm. Mean length was 7.6 cm. The mean time for needed external skeletal fixation was 20 d/cm. The mean time of osteogenesis was 56 d/cm. For complications, there were 3 tibias ununion cases and 1 varus ankle. All cases were treated undergoing twice.</p><p><b>CONCLUSIONS</b>The method reduces the time for needed external skeletal fixation visibly, enhances the quality of limb lengthening remarkably, prevents complications of shortening new bone, deformity, bending and re-fracture which do not effect the healing time. This is a new choice of limb lengthening.</p>