Aim To evaluate the efficacy of the combination of leonurine(SCM),polygonatum polysaccharide(PSP)and deoxynojirimycin(DNJ)in hypoglycemic and antithrombotic aspects by establishing and using zebrafish type II diabetes combined with thrombosis model. Methods On the basis of the zebrafish type II diabetes model established by streptozotocin,phenylhydrazine(PH),arachidonic acid(AA)and ponatinib(PT)were used respectively to establish thrombosis models,which were divided into control group,model group,metformin+aspirin group,and the high,medium and low concentration groups of the combination drugs. After drug intervention in the experimental group,the thrombosis of tail vein was observed. Kit was used to determine the sugar content of juvenile fish tissues in each group. Quantitative analysis of cardiac erythrocytes by o-dianisidine staining method was used to calculate the inhibition rate of thrombus. Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of related genes in zebrafish. Results Compared with the model group,the combined drug could significantly increase the staining intensity of erythrocytes in zebrafish hearts,inhibit thrombosis,down-regulate the expression of thrombosis-related genes,and reduce tissue glucose content. Conclusions The combined use of the three drugs can effectively reduce the tissue sugar content and have antithrombotic effect,which show great potential in the development of drugs for the treatment of type II diabetes and thrombosis.

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

OBJECTIVE: To explore the risk factors, clinical characteristics, precaution and treatment of hyper perfusion syndrome (HPS) after carotid artery stenting (CAS). METHODS: From September 2014 to March 2018, the clinical data of 226 patients with severe carotid stenosis (70%-99%) treated with carotid artery stenting (CAS)at Department of Interventional Radiology and Vascular Surgery, Peking University Third Hospital, were analyzed retrospectively．Five of them developed HPS after CAS．The relationship between the clinical baseline data, imaging characteristics, perioperative management and HPS were assessed. RESULTS: In this group, 5 patients of them (2.21%, 5/226) developed HPS after CAS, and 2 patients of them (0.88%, 2/226) were hyper perfusion induced intracranial hemorrhage (HICH). The 5 patients consisted of 4 men and 1 woman whose age ranged from 58 to 74 years. The symptoms of HPS occurred within 4 hours to 3 days after CAS. Among the 5 cases, the clinical manifestations were that 2 cases with headache, 1 case with delirium,1 case with hemiparesis of left limbs, and 1 case with coma(died ultimately).The main manifestations of case 1 and case 2 were headache in the frontal parietal temporal region of the operative side, accompanied by nausea and vomiting. The symptoms were relieved after blood pressure lowering treatment and mannitol dehydration. The main manifestations of case 3 were excitement and delirium. The symptoms were relieved by a small dose of sedatives, also with blood pressure lowering treatment and mannitol dehydration. The initial symptoms of case 4 were excitement and delirium, accompanied by mild headache of the operative side, and hemiplegia of the contralateral limb occurred within a short time. The main manifestation of case 5 was severe headache and went into deep coma within a short time. This patient died of massive cerebral hemorrhage ultimately. CONCLUSION HPS is an uncommon but serious complication after CAS. Improving our understanding and heightening vigilance of HPS is necessary. The earlier diagnosis, the earlier treatment.
Aged ; Carotid Arteries ; Carotid Artery, Common ; Carotid Stenosis/surgery* ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stents

OBJECTIVE: To assess the safety and efficacy of Neuroform EZ stent used in treatment of symptomatic complex severe intracranial atherosclerotic stenosis (ICAS). METHODS: Clinical data of 18 patients with symptomatic complex severe ICAS undergoing Neuroform EZ stent angioplasty from January 2016 to December 2017 were retrospectively analyzed. All the lesions of the patients in this group were considered as complex ICAS, i.e. with severe tortuous access, long (>10 mm) or occlusive or bifurcation lesions, with concurrent aneurysms near the stenotic lesion. The primary outcome was defined as any stroke (including ischemic or hemorrhagic) or deaths from any cause after stenting procedure within 30 days. The secondary outcome was defined as successful revascularization and occurrence of >50% in-stent restenosis during the follow-up period. RESULTS: All the 18 patients achieved technical success (100%) and mean stenosis rate was reduced from 85%±7% to 18%±6%. Of the 18 patients included, the 30-day stroke or death was 5.6% (1/18), which presented as basal ganglia region infarction in a patient with tandem lesions on the left vertebral artery. There was no hemorrhagic and death complications that occurred in the patients of this group. One concurrent aneurysm was embolized with micro coil (stent assisted) by stages after 1 month. In this group 12 patients were followed up with digital subtraction angiography (DSA) after hospital discharge. The follow-up period ranged from 8 months to 26 months [mean: (16±8) months]．During the follow-up period 2 patients in the 12 patients (2/12, 16.7%) developed in-stent restenosis (ISR) confirmed by DSA, and one of them was symptomatic restenosis and restored unobstructed blood flow after balloon angioplasty. CONCLUSION Neuroform EZ stent for the treatment of highly screened symptomatic complex severe ICAS is safe and effective. It has its advantages over traditional stent.
Cerebral Angiography ; Constriction, Pathologic ; Follow-Up Studies ; Humans ; Retrospective Studies ; Stents ; Treatment Outcome

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
Aged ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Methylation ; Middle Aged ; Muscle Proteins/metabolism* ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Progression-Free Survival ; Prostatectomy ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

Objective To investigate whether gastroesophageal reflux can cause asthma-like pathophysiological changes and its mechanism.Methods Sixty BALB/c mice were randomly divided into 4 groups:group A was gastroesophageal reflux control group,group B was asthma control group,group C was gastroesophageal reflux group,and group D was asthmatic group.The asthmatic models were replicated with ovalbumin(OVA) and aluminum hydroxide,and gastroesophageal reflux models were replicated with hydrochloric acid solution pepsin.After the last inhaling ovalbumin and slow perfusion,the airway pressure was detected,and eosinophil (EOS) and neutrophil granulocyte in bronchial lavage fluid were counted.The flow cytometer was used to determinate IL-4,IFN-γ,and Th1/Th2 ratio changes of spleen cells;Lung tissue and esophagus sections were stained with HE,and pathological changes of lung tissue and esophagus were observed.Results In group C and group D,the airway hyper-responsiveness was significantly increased compared with group A and group B,and the differences were statistically significant (all P ＜ 0.05).In group C and group D,IL-4were significantly increased,while IFN-γand Thl/Th2 ratio were significantly decreased than that in the group A and B group,the differences were statistically significant (all P ＜ 0.05).EOS of group C and group D accounted for a high percentage of total cells and they were significantly higher than that in group A and group B,and the differences were statistically significant (all P ＜ 0.05).Through lung tissue biopsy,in group C and group D,bronchial lumen deformation,infiltration of inflammatory cells around the wall,basement membrane thickening,inflammatory cell infiltration around the wall,peripheral vascular edema,enlarging alveolar cavity,alveolar wall thinning,fracture,part of alveolar fusion into bullace of lung,could be observed.The lung pathological section showed that the endothelial cells in group A and group B were integrated and had no denaturation or necrosis,and there was no inflammation cell infiltrate around.EOS biopsy could be observed in group A and group B of lower esophagus markedly submucosal edema,submucosal inflammatory cell infiltration,and keratin hyper function,visible bacteria group A group B and group D were basic ally normal,with no pathological changes.Conclusions Gastroesophageal reflux can induce Th1/Th2 decreasing,airway hyper-responsiveness and pathophysiological changes similar to asthma.

OBJECTIVETo observe the effect of moxibustion at Sanyinjiao (SP 6) on delivery stage of primipara.

METHODSSixty cases of primipara were divided into a moxibustion at Sanyinjiao group, a non-acupoint group and a blank group. When the diameter of wormb mouth opened to 2-3 cm, showing that it entered into active stage of uterine contraction, moxibustion at Sanyinjiao (SP 6) for primipara was applied in moxibustion at Sanyinjiao group; moxibustion was applied at 1 cun towards radialis from the region where 2 cun above Kongzui (LU 6) in non-acupoint group, 30 minutes treatment was for both groups. There was no intervention in blank group. After delivery, the time of first,second and third delivery stages and postpartum bleeding 2 hours after delivery were compared among three groups.

RESULTSThe active duration of first delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (P < 0.05, P < 0.01); the duration of the second delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (both P < 0.05) as well; the postpartum bleeding 2 hours after delivery in moxibustion at Sanyinjiao group was less than other two groups and the difference was statistic significant between moxibustion at Sanyinjiao group and blank group (P < 0.05).

CONCLUSIONBy moxibustion at Sanyinjiao (SP 6), the active duration of first delivery stage and the duration of second delivery stage are markedly shortened, postpartum bleeding 2 hours after delivery is obviously reduced, and the safety of vaginal delivery is increased.

Acupuncture Points ; Adult ; Delivery, Obstetric ; Female ; Humans ; Labor Onset ; Moxibustion ; Postpartum Hemorrhage ; therapy ; Pregnancy ; Young Adult

OBJECTIVETo explore the effect of moxibustion at Sanyinjiao (SP 6) on normal process of childbirth and safety of mothers and infants.

METHODSOne hundred and seventy-four cases of singleton primiparas, fetal head position were selected as the subjects and divided into three groups by single-blind randomized method: an acupoint group (n = 59), a non-acupoint group (n = 57) and a blank group (n = 58). When the cervix was dilated by 2 to 3 cm, DAJ-23 type multi-function moxibustion apparatus was used at Sanyinjiao (SP 6) in acupoint group, and at non-acupoint spot (the midpoint from the radial arterial pulse throbbing place on the radial side of the transverse crease of the wrist to the radial end of biceps tendon of the elbow) in non-acupoint group, 30 min for each one. The conventional labor care was adopted in blank group. The differences were observed in the first active stage, the second stage and the third stage of the labor as well as the safety of mothers and infants among three groups.

RESULTSThe durations of the first active stage of labor [(123.05 +/- 96.401) min] and the second stage [(37.407 +/- 22.390) min] in acupoint group were shorter than those [(171.40 +/- 94.339) min, (49.517 +/- 25.373) min] in non-acupoint group, as well as those [(178.79 +/- 97.231) min, (53.684 +/- 20.087) min] in blank group separately (all P < 0.05). It was discovered that the progressions of the first active stage and the second stage of labor were accelerated in acupoint group, and there was no statistically significant difference in the third stage of labor among the three groups (all P > 0.05). Bleeding amount after childbirth in acupoint group was less than those in non-acupoint group and blank group (both P < 0.05), and Apgar scores of newborns in acupoint group and non-acupoint group were higher than that in blank group (both P < 0.05).

CONCLUSIONMoxibustion at Sanyinjiao (SP 6) can shorten the process of childbirth, reduce postpartum bleeding and has no harmful impact on mothers and infants.

Acupuncture Points ; Adult ; Female ; Humans ; Labor, Obstetric ; Moxibustion ; Pregnancy ; Young Adult

OBJECTIVETo observe the effect of acupoint Sanyinjiao (SP6) moxibustion (S-Mox) on the duration of the first labor stage and uterine contractive pain in primiparae.

METHODSSixty primipara women in labor were equally assigned according to their choice to three groups: women in the S-Mox group received bilateral S-Mox for 30 min, women in the non-acupoint group received moxibustion (Mox) applied on non-acupoints for 30 min, and those in the control group did not receive Mox intervention. The duration of the first labor stage was recorded and the degree of labor pain was estimated by a visual analogue scale (VAS) before and after Mox.

RESULTSThe duration of the first stage active phase in the S-Mox group was significantly shorter than that in the other two groups (P<0.05, P<0.01); the VAS score after Mox was lower in the S-Mox group, showing a statistical difference in comparison with the control group (P<0.05).

CONCLUSIONSApplying S-Mox could markedly shorten the active phase of the first stage of labor and lower the VAS score of uterine contractive pain, which means alleviating the pain caused by vaginal delivery. Its mechanism is worthy of further study.

Acupuncture Points ; Adult ; Female ; Humans ; Labor Pain ; physiopathology ; therapy ; Labor Stage, First ; physiology ; Moxibustion ; Pain Measurement ; Parity ; Pregnancy ; Uterine Contraction ; physiology ; Young Adult