Objective:To compare the efficacy of pecto-intercostal fascial plane (PIFP) block versus transversus thoracic muscle plane (TTP) block under ultrasound guidance in coronary artery bypass grafting with general anesthesia.Methods:Ninety American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ patients of either sex, aged 50-79 yr, scheduled for elective coronary artery bypass grafting, were divided into 3 groups ( n=30 each) using a random number table method: PIFP block combined with general anesthesia group (PG group), TTP block combined with general anesthesia group (TG group), and general anesthesia group (G group). After anesthesia induction, bilateral PIFP block was performed under ultrasound guidance in group PG, TTP block was performed under ultrasound guidance in group TG. Three groups used the same general anesthesia method and patient-controlled intravenous analgesia after surgery. Visual analog scale scores (cough, position change, etc) at rest and during activity were recorded at 6, 12, 18 and 24 h after operation. The total consumption of intraoperative sufentanil, extubation time, length of stay in intensive care units, rate of rescue analgesia, effective pressing times of patient-controlled analgesia, incidence of postoperative nausea and vomiting, skin pruritus and nerve block-related adverse events were recorded. The operation time of nerve block was recorded and ultrasound-guided needle visibility score was assessed in PG group and TG group. Results:Compared with group G, the total consumption of intraoperative sufentanil was significantly reduced, the extubation time and length of stay in intensive care units were shortened, visual analog scale scores at rest and during activity were decreased at 6, 12 and 18 h after operation, the rate of rescue analgesia was decreased, and the effective pressing times of patient-controlled analgesia were decreased in group PG and group TG ( P<0.05), and no significant change was found in the aforementioned parameters in PG and TG groups ( P> 0.05). Compared with group TG, the operational time of nerve block was significantly shortened, and the ultrasound-guided needle visibility score was increased in group PG ( P<0.05). No nerve block-related adverse events were found in PG and TG groups. There was no significant difference in the incidence of postoperative nausea and vomiting and skin pruritus among the three groups ( P>0.05). Conclusions:PIFP block can provide good perioperative analgesia and promote the rapid recovery in the patients undergoing coronary artery bypass grafting with general anesthesia. Although the analgesic effect of PIFP blockade is similar to that of TTP blockade, PIFP blockade is more clinically valuable due to its simpler operation and less relative risk.

Objective:To evaluate the correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation (rScO 2) in elderly patients undergoing coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods:Sixty-four elderly patients undergoing elective CABG under CPB, aged 60-80 yr, regardless of gender, with body mass index of 18.1-28.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, with left ventricular ejection fraction≥50%, were selected. The rScO 2 and ultrasonic parameters of internal carotid artery including peak systolic velocity (PSV-ICA), end-diastolic velocity (EDV-ICA), diameter (D-ICA) and blood flow volume (Q-ICA) were recorded before anesthesia induction (T 0), at surgical skin incision (T 1), at 30 and 60 min of CPB (mean value was calculated, T 2), and at 30 and 60 min after termination of CPB (mean value was calculated, T 3). The ratio of unilateral internal carotid artery blood flow to cardiac output (Q/CO) was calculated. The receiver operating characteristic curve was used to analyze the accuracy of ultrasound parameters of internal carotid artery blood flow in predicting rScO 2 < 60%. Results:PSV-ICA was positively correlated with rScO 2 at T 0, T 1 and T 3 ( P<0.05), but no correlation was found between PSV-ICA and rScO 2 at T 2 ( P>0.05). There was no correlation between EDV-ICA and rScO 2 at each time point ( P>0.05). Q-ICA was positively correlated with rScO 2 at each time point ( P<0.05). Q/CO was not correlated with rScO 2 at T 1 ( P>0.05), but Q/CO was positively correlated with rScO 2 at T 2 and T 3 ( P<0.05). During the non-CPB period (T 0, T 1, T 3), the cutoff values of PSV-ICA and Q-ICA in predicting rScO 2< 60% were 51.35 cm/s and 283.5 ml/min respectively, the sensitivity was 0.900 and 0.900 respectively, and the specificity was 0.610 and 0.857 respectively (AUC=0.761, P=0.006; AUC=0.903, P< 0.001). During the CPB period, the cutoff values of Q-ICA and Q/CO in predicting rScO 2<60% were 296.5 ml/min and 5.84% respectively, the sensitivity was 0.900 and 0.800, and the specificity was 0.545 and 0.659 (AUC=0.764, P=0.001; AUC=0.748, P=0.002), respectively. Conclusions:PSV-ICA and Q-ICA are positively correlated with rScO 2 during the non-CPB period, and Q-ICA and Q/CO are positively correlated with rScO 2 during the CPB period in elderly patients undergoing CABG. PSV-ICA, Q-ICA and Q/CO can accurately predict rScO 2<60%.

OBJECTIVE To explore the regulatory effect of syringic acid in cholestatic mice based on bile acid metabolism and intestinal barrier.METHODS Twenty mice were randomly divided into control group,model group and low and high dose of syringic acid(70,140 mg·kg-1)groups.Intrahepatic cholestasis was induced by intraperitoneal injection of α-naphthalene isothiocyanate af-ter 2 h of administration on the fifth day.After the last dose,the changes of body weight and liver mass of mice were recorded.Liver function indexes in serum and histopathology were detected,qPCR verified the expression of tight junction proteins Zonula Occludens Protein 1(ZO-1),Occludin and Claudin-5 in mouse colon tissues,the changes of metabolites in serum were analyzed by using nontar-geted metabolomics,and the changes of total bile acids in liver and feces were detected.RESULTS Syringic acid could significantly reduce the serum alanine aminotransferase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP)activity,total biliru-bin(TBIL)and direct bilirubin(DBIL)levels(P<0.05,P<0.01)in the model group mice,and reduce liver damage and necrosis.Syringic acid reduced lymphocyte infiltration in the colon of mice in the model group and restored crypt morphology,while the high-dose syringic acid group significantly increased the mRNA expression levels of ZO-1,Occludin,and Claudin-5 in the colon(P<0.05).The high-dose intervention of syringic acid significantly upregulated 11 metabolites and 29 metabolites,and the metabolites mainly involved the biosynthesis of secondary metabolites,secondary bile acid biosynthesis and bile secretion pathways.Syringic acid reduced the content of total bile acids in the liver and increased the excretion of total bile acids in feces(P<0.05,P<0.01).CON-CLUSION Syringic acid can significantly improve the phenotype of cholestasis in cholestatic mice,improve the damage of intestinal barrier,and promote the metabolism of bile acids in cholestatic mice,which may be the key pathway for syringic acid to improve chole-stasis.

Objective To assess the impact of intravenous esketamine administered prior to car-diopulmonary bypass(CPB)initiation on ventricular function and internal carotid artery blood flow in pa-tients undergoing heart valve replacement surgery.Methods Sixty patients underwent elective CPB heart valve replacement,38 males and 22 females,aged 18-75 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅱ or Ⅲ,NYHA cardiac function classification Ⅰ-Ⅲ,and a left ventricular ejection fraction(LVEF)of≥45％,were selected.The patients were randomly divided into two groups:esketamine group(group E)and normal saline group(group C),30 patients in each group.Total intravenous anesthesia was used during the operation.Following the initiation of CPB,group E received an intravenous infusion of es-ketamine at a rate of 0.5 mg·kg-1·h-1 until the conclusion of the procedure,while group C received an equivalent volume of normal saline concurrently at the same rate.HR,MAP,CVP,and cardiac output index(CI)were recorded before anesthesia induction,during skin resection,and within 60 minutes after stopping CPB.LVEF,left ventricular global longitudinal strain(GLS),global longitudinal time-to-peak strain standard deviation(GLTSD),global circumferential strain(GCS),global circumferential time-to-peak strain standard deviation(GCTSD),right ventricular ejection fraction(RVEF),right ventricular GLS,and GLTSD were obtained during skin resection,within 40 minutes of CPB,and 60 minutes after stopping CPB.rScO2,BIS,concentrations of Hb and lactic acid(Lac),peak systolic flow velocity(SPV),quantity of flow-internal carotid artery(Q-ICA),and blood flow resistance index(RI)were recorded before anesthesia induction,during skin resection,within 40 minutes of CPB,and within 60 minutes after stopping CPB.Concentrations of cardiac troponin Ⅰ(cTnⅠ),alanine aminotransferase(ALT),creatinine(Cr),and neuron-specific enolase(NSE)were recorded before anesthesia induction and 6 hours after operation.Spon-taneous resuscitation after CPB,postoperative extubation time,duration of ICU stay,total hospital stay,in-cidence of adverse cardiac events,and 30-day postoperative mortality were recorded.Results Compared with group C,group E exhibited a significant increase in CI within 60 minutes after stopping CPB(P＜0.05).The LVEF,RVEF,and right ventricular GLS demonstrated significant increases within 60 minutes after stopping CPB in group E compared with group C(P＜0.05).The left ventricular GLS and left ven-tricular GCTSD displayed significant increases 30 minutes after stopping CPB in group E compared with group C.The RI exhibited a significant increase within 40 minutes of CPB in group E compared with group C(P＜0.05).There were no significant differences in cTnⅠ,ALT,Cr,NSE,spontaneous resuscitation affter CPB,postoperative extubation time,duration of ICU stay,total hospital stay,incidence of cardiac adverse events,and 30-day postoperative mortality between the two groups.Conclusion Administration of esket-amine following the onset of CPB in patients undergoing cardiac surgery demonstrates a significant elevation in CI post-CPB cessation.Furthermore,it may augment ventricular longitudinal strain,thereby enhancing myocardial contraction,leading to increased postoperative ventricular ejection fraction,and sustaining hemo-dynamic stability.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective To compare the effects of dobutamine with those milrinone on myocardial strain in patients undergoing valve replacement surgery.Methods Fifty-five patients udergoing valve replacement surgery, 27 males and 28 females, aged 40-75 years, falling into ASA physical statusⅡ orⅢ, New York Heart Association (NYHA) ⅡorⅢ, were included in this study.They were divided into 3 groups by using a random number table:intravenous infusion dobutamine group (group D, n=18), intravenous infusion milrinone group (group M, n=20) and intravenous infusion saline group (group C, n=17).All patients were used general anesthesia.In groups D, the patients received intravenous infusion dobutamine (4μg·kg-1·min-1) for an hour starting from 15 min after termination of CPB.In group M, the patients did intravenous infusion milrinone (0.4μg·kg-1·min-1) in the same way.In group C, the patients got intravenous infusion saline also.After induction of anesthesia, these patients were recorded for hemodynamic measurement at three points after induction of anesthesia and before splitting of sternum (T0), starting from 15 min after termination of CPB (T1), intravenous infusion medicine for 30 min (T2), intravenous infusion medicine for one hour (T3):HR, CVP, cardiac output (CO), left ventricular ejection fraction (LVEF), right ventricular fractional area change (RVFAC), cardiac index (CI) and systemic vascular resistance index (SVRI) and strained indicator:global longitudinal strain of left ventricle (S-LVL), global circumferential strain of the left ventricle (S-LVM), global longitudinal strain of right ventricle (S-RV).Results Compared with group M, HR in group D at T2 and T3 was higher (P<0.05).Compared with group C, HR in group D at T3 was higher (P<0.05).And CI in group D at T2 was higher than that in groups C and M (P<0.05).Compared with groups C, S-LVMin groups D and M at T2 and T3 were stronger, S-LVL, S-RV in group D and S-RV in group M at T3 were stronger (P<0.05).Conclusion Intravenous infusion dobutamine can improve S-LVM, S-LVLand S-RV;Intravenous infusion milrinone can improve S-LVMand S-RV.

Objective To investigate the effects of intravenous infusion of methoxamine and phenylephrine on blood pressure and coronary artery blood flow in elderly patients with post volume treatment hypotension after cardiopulmonary bypass (CPB ) undergoing coronary artery bypass grafting (CABG).Methods Forty patients,physical status ASA Ⅱ or Ⅲ,>65 years old,undergo-ing CABG,following CPB,with a mean arterial pressure (MAP)<70% of baseline,despite adequate volume replacement (based on achieving a normal CVP),were randomly assigned to me-thoxamine group (group M,n=20)or phenylephrine group (group P,n=20).The initial infusion rate was 3 μg·kg-1·min-1in group M and 0.24 μg·kg-1·min-1in group P,respectively.The rate was increased or decreased by one third of initial dose in order to maintain the MAP at the target level (±20% of baseline MAP).Coronary sinus (CS),systolic blood flow velocity time integral (SV-TI),diastolic velocity time integral (DVTI),CS blood flow (CSBF)were recorded before adminis-tration,at 3,5,10,15,30 min after administration.Results Compared with pre-administration,SV-TI,DVTI,CSBF were increased at each point in the two groups (P<0.05 or P<0.01).SVI was in-creased at 15 min and 30 min in group M (P<0.05).Compared with group P,DVTI and CSBF at 10,15 min and 30 min was higher in group M (P<0.05 or P<0.01).There were 2 cases of atrial fibrillation and 1 case of frequent ventricular premature beat after operation in group M;1 case of bradycardia and 1 case of frequent ventricular premature beats after operation in group P.Conclusion Intravenous infusion of methox-amine and phenylephrine both can correct post volume treatment hypotension after CPB in elderly patients undergoing CABG,but methoxamine increases coronary blood flow more significantly and may be more ben-eficial to patients with coronary heart disease.

Objective To evaluate the effect of dobutamine or milrinone on intraventricular syn-chronization in the patients undergoing cardiac valve replacement with cardiopulmonary bypass ( CPB). Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes, aged 40-75 yr, of New York Heart AssociationⅡorⅢ, scheduled for elective cardiac valve replacement with CPB, were divided into 3 groups (n＝20 each) using a random number table: control group ( group C), dobutamine group ( group D) and milrinone group ( group M). Dobutamine 4 μg·kg-1·min-1was intravenously infused for 60 min starting from 15 min after termination of CPB in group D. Milrinone 0. 4 μg·kg-1·min-1was intravenously infused for 60 min starting from 15 min after termination of CPB in group M. The equal volume of normal saline was given instead in group C. The parameters of heart function were monitored using transesophageal echocardiography. After induction of anesthesia and before splitting the sternum (T0), at 15 min after termination of CPB (T1), and at 30 and 60 min of dobutamine, milri-none or normal saline infusion (T2, average value at two time points), the parameters of intraventricular synchronization were calculated with QLAB software (9. 1 version): standard deviation of time to peak sys-tolic velocity of the left ventricular longitudinal strain 7 segments (LVSDt-L), standard deviation of time to peak systolic velocity of the right ventricular longitudinal strain 7 segments (RVSDt), standard deviation of time to peak systolic velocity of the left ventricular circumferential strain 6 segments (LVSDt-C). Results Compared with group C, LVSDt-C, LVSDt-L and RVSDt were significantly decreased at T2in group D (P＜0. 05), and no significant change was found in the indices mentioned above at each time point in group M (P＞0. 05). RVSDt was significantly higher at T2in group M than in group D ( P＜0. 05). Compared with the baseline at T0, LVSDt-L was significantly increased at T2in group C, and RVSDt was significantly in-creased at T2in group M ( P＜0. 05). Conclusion Intravenously infusing dobutamine after CPB can im-prove the ventricular synchronization, however, intravenously infusing milrinone may increase the right ventricular asynchronization in the patients undergoing cardiac valve replacement.

The elaboration of the mechanism and pharmacodynamic substance are the main obstacles to the modernization of Chinese medicine.The rich ingredient of Chinese medicine is almost attention,with a research strategy of forward pharmacology.This strategy often neglects the study of trace components of Chinese medicine.Synthetic lethality,a extremely complex gene interactions,is to magnify the effects of the co-regulation of biological effects (＞ 1 000 times).The theory of synthetic lethality has achieved good results in the development of anti-tumor drugs,including the discovery of PARP inhibitors,the clinical use of chemotherapy drug addition and attenuation combination.In view of this,this research model may be used to elucidate trace effective substance.Based on the reverse thinking of "targetcomponent-effect"and clear synergistic targets,the mechanism of traces and weak-potency substance of traditional Chinese medicine was studied,and the synergistic combination of potential was found.

Aim To screen the potential inhibitors of post-transcriptional activity of pro-inflammatory media-tor TNF-α from the lipophilic constituents in Chinese Medicine Salvia miltiorrhiza Bunge ( Danshen) , we es-tablished dual luciferase reporter gene system pGL3-TNF-α3′UTR ( 3′untranslated region ) co-transfected with Renilla control gene. Methods Complementary DNA ( cDNA) template was obtained from human um-bilical vein endothelial cells ( HUVECs ) . The full length DNA of TNF-α 3′-UTR was amplified through PCR, and then connected the luciferase reporter vector pGL3-control after enzyme digestion. pGL3-TNF-α 3′UTR constructs were co-transfected with pSVRenilla into the mononuclear macrophages RAW264. 7 cells. The relative activity of reporter genes was measured by dual luciferase reporter ( DLR ) assay system after the stimulus of lipopolysaccharide ( LPS ) in presence or absence of tanshinones compounds. Results The pGL3-TNF-α3′UTR luciferase reporter gene was suc-cessfully constructed. The cloning DNA fragment and sequence were both consistent with the GENBANK da-tabase. LPS significantly induced the relative reporter activityof RAW264 . 7 cells transfected with pGL3-TNF-α 3′UTR. Among four tanshinones compounds, we found only cryptotanshinone could significantly de-crease LPS-induced relative reporter activity. Conclu-sion The pGL3-TNF-α 3′UTR construct combined with DLR assay system was successfully established, which can be used to discover the agents such as cryp-totanshinone that regulate the post-transcription of TNF-α in treatment of inflammatory and malignant dis-eases.