Objective : To investigate the protective effect of adiponectin APN on myocardial injury caused by sep⁃ sis and its possible mechanism. : Methods Results : Compared with sham group , the expression of Bax , cleaved Caspase3 protein increased and the expression of Bcl⁃2 protein decreased in LPS group. Compared with LPS group , the injury in APN + LPS group was significantly alleviated , showing that the expression of Bax , cleaved caspase3 protein decreased and the expression of Bcl⁃2 protein increased. Meanwhile , compared with sham group , the expression of Cx43 increased in LPS group and decreased in APN + LPS group. Conclusion Adiponectin can attenuate LPS⁃induced cardiac injury in septic mice. The mechanism may be through the inhibition of apoptotic signal pathway and the expression of Cx43.

Objective:To investigate the effect and safety of Guanxinning tablets combined with antiplatelet therapy on acute coronary syndrome. Methods:A total of 120 patients with acute coronary syndrome who received treatment in Shulan (Hangzhou) Hospital from January 2021 to December 2021 were included in this study. They were randomly divided into a control group and a study group ( n = 60/group). The control group was treated with antiplatelet drugs clopidogrel and aspirin. The study group was treated with clopidogrel, aspirin and Guanxinning tablets in combination. All patients were treated for 3 months. The levels of blood lipids (high-density lipoprotein cholesterol, total cholesterol, triglyceride, low-density lipoprotein cholesterol), C-reactive protein, tumor necrosis factor-α, endothelin-1, and vascular endothelial growth factor measured before and after treatment as well as the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride in each group were significantly decreased compared with those measured before treatment (all P < 0.05). After treatment, serum level of high-density lipoprotein cholesterol in each group was significantly increased compared with that measured before treatment ( P < 0.05). After treatment, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglyceride in the control group were (4.36 ± 1.01) mmol/L, (3.02 ± 0.28) mmol/L, and (1.98 ± 0.12) mmol/L respectively which were significantly higher than (3.98 ± 1.05) mmol/L, (2.52 ± 0.42) mmol/L, (1.58 ± 0.23) mmol/L in the study group ( t = -2.02, -7.67, -11.94, all P <0.05). Serum level of high-density lipoprotein cholesterol in the control group was significantly lower than that in the study group [(1.26 ± 0.08) mmol/L vs. (2.36 ± 0.16) mmol/L, t = 47.63, P < 0.001). After treatment, serum levels of C-reactive protein and endothelin-1 in the control group were (5.62 ± 0.56) mg/L and (86.24 ± 12.68) pg/L, respectively, which were significantly higher than (4.32 ± 0.82) mg/L and (75.26 ± 12.46) pg/L in the study group, ( t = -10.14, -4.78, both P < 0.001). After treatment, serum levels of tumor necrosis factor-α and vascular endothelial growth factor in the control group were (5.62 ± 0.56) mg/L and (76.28 ± 13.52) pg/L, which were significantly lower than (8.76 ± 1.06) mg/L and (86.32 ± 13.46) pg/L in the study group ( t = 20.23, 4.08, both P < 0.05). The incidence of adverse reactions in the study group was significantly lower than that in the control group [5.00% (3/60) vs. 8.33% (5/60), χ2 = -0.54, P > 0.05). Conclusion:Guanxinning tablets combined with antiplatelet has a remarkable therapeutic effect on acute coronary syndrome. It is highly safe and has a clinical application value.

Objective: To investigate the role of connexin 43 ( Cx43) in acute sympathetic stress induced by phe- nylephrine (PE) overactivation of α1-adrenergic receptor ( α1-AR) in cardiomyocytes． Methods: Cardiomyocytes of H9C2 rats were randomly divided into control group，PE alone treatment group，Gap26 ( Cx43 specific inhibitor) intervention group and Gap26 alone treatment group．PE alone treatment group was treated with 50 μmol / L PE for 15 min．The Gap26 intervention group was pretreated with 0. 5 μmol / L Gap26 for 30 min，and then treated with 50 μmol / L PE for 15 min．The protein and mRNA expression levels of Cx43，NLRP3 inflammasome，interleukin-1 β (IL-1 β) ，Caspase-1，interleukin-18 (IL-18 ) were detected by Western blot and qRT-PCR. The expression and co-location of Cx43 in cardiomyocytes were observed by immunofluorescence assay，and the expression of inflamma- tory cytokines IL-1 β and IL-18 in cardiomyocytes was detected by ELISA. Results: Compared with control group， the protein and mRNA levels of Cx43，NLRP3，Caspase-1 and IL-18 in PE group increased．Compared with PE a- lone treatment group，the protein and mRNA levels of Cx43，NLRP3，Caspase-1 and IL-18 decreased after Gap26 intervention，but they were still higher than those of control group． Similarly ，immunofluorescence showed that Cx43 protein expression increased in PE alone group，while Cx43 expression was down-regulated in Gap26 inter- vention group compared with PE alone group．ELISA results showed that the expression of IL-1 β and IL-18 was sig- nificantly up-regulated in PE alone group，but down-regulated in Gap26 intervention group． Conclusion Cx43 is involved in α1-AR activation induced cardiac acute sympathetic stress by regulating NLRP3 inflammasome.

【Objective】 To study the mechanism of Apocynum leaves in the treatment of sepsis by network pharmacology method in order to explore the multi-dimensional research method of Xinjiang ethnic medicine treatment of infectious diseases and provide scientific theoretical basis for clinical medication. 【Methods】 TCMSP and literature collection were used to screen the main active components of Apocynum venetum leaf, and target prediction analysis was conducted by SwissTarget Prediction database. We used Genecards database to screen relevant targets for sepsis, used Omicshare to calculate Venn figure of the intersection targets, constructed the protein-protein interaction network diagram in the STRING database, used Ensembl for name conversion of protein targets, then entered Omicshare server for Go function and KEGG pathway enrichment of dynamic analysis. Last we used Cytoscape3.6.0 software to construct "Apocynum venetum leaf-the active ingredients-targets-Go-KEGG-sepsis" network to explore the mechanism of action of Apocynum’s resistance to sepsis. 【Results】 Kaferol, luteolin, proanthocyanidin B1 and phytosterol in Apocynum venetum leaves may treat sepsis by controlling signal transduction, regulating hormone level and anti-infection through predictive biological targets such as Akt1, VEGFA, MAPK3, EGFR, Src and PTGS2. They can play an important role through VEGF, EGFR, erbB, HIF-1, RAS and other enrichment pathways. 【Conclusion】 The active components of Apocynum venetum leaves can fight against sepsis through multiple targets and multiple pathways.

Objective:To evaluate the relationship between transforming growth factor beta-3 (TGF-β 3)/mammalian homologs of the drosophila mad gene 3 (Smad3) signaling pathway and neuronal apoptosis during reduction of focal cerebral ischemia-reperfusion (I/R) injury by isoflurane postconditioning (ISO) in rats. Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 210-230 g, were randomly divided into 5 groups ( n=12 each): sham operation group (group S), cerebral I/R group (group I/R), cerebral I/R plus isoflurane postconditioning group (group I/R+ ISO), cerebral I/R plus pirfenidone group (group I/R+ P), and cerebral I/R plus isoflurane postconditioning plus pirfenidone group (group I/R+ ISO+ P). Local cerebral I/R was produced by middle cerebral artery occlusion for 1.5 h followed by 24-h reperfusion in anesthetized rats.Pirfenidone 5 μg/kg was injected into the lateral ventricle at 30 min before ischemia in I/R+ P and I/R+ ISO+ P groups.In I/R+ ISO and I/R+ ISO+ P groups, 1.5% isoflurane was inhaled for 1 h starting from the time point immediately after onset of reperfusion.Neuro-functional deficit was assessed using neurologic deficit scores (NDS) at the end of reperfusion.Then the animals were sacrificed, and brain tissues were removed for determination of the neuronal damage rate (by Nissl staining), neuronal apoptosis rate (by TUNEL), expression of TGF-β 3 (using immunofluorescence), and expression of TGF-β 3, phosphorylated Smad3 (p-Smad3), caspase-3, Bax and Bcl-2 (by Western blot). Results:Compared with group S, the NDS, neuronal damage rate and apoptosis rate of neurons were significantly increased, the expression of TGF-β 3, caspase-3 and Bax was up-regulated, and the expression of p-Smad3 and Bcl-2 was down-regulated in group I/R ( P<0.05). Compared with group I/R, the NDS, neuronal damage rate and apoptosis rate of neurons were significantly decreased, the expression of TGF-β 3, p-Smad3 and Bcl-2 was up-regulated, and the expression of caspase-3 and Bax was down-regulated in group I/R+ ISO, and the NDS, neuronal damage rate and apoptosis rate of neurons were significantly increased, the expression of TGF-β 3 and p-Smad3 was down-regulated, and the expression of caspase-3 was up-regulated in group I/R+ P ( P<0.05). Compared with group I/R+ ISO, the NDS, neuronal damage rate and apoptosis rate of neurons were significantly increased, the expression of TGF-β 3, p-Smad3 and Bcl-2 was down-regulated, and the expression of caspase-3 and Bax was up-regulated in group I/R+ ISO+ P ( P<0.05). Conclusion:Isoflurane postconditioning can inhibit neuronal apoptosis by activating the TGF-β 3/Smad3 signaling pathway, thus reducing focal I/R injury in rats.

Objective: The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BK_Ca expression and function on cochlear pericytes and their relationship with age-related hearing loss. Methods: Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BK_Ca in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BK_Ca current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software. Results: Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant (P<0.01). Compared with the control group, the expression of BK_Ca in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27±0.03,the difference was statistically significant P<0.01), and the cell current density and BK_Ca net current value were also significantly reduced with statistically significant (P<0.01). Conclusions D-galactose can successfully induce guinea pig aging model, in which BK_Ca expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BK_Ca expression and function may be related to age-related hearing loss.

Clinical medicine is a practical, highly skilled natural science. Solid clinical skills are the cornerstone of medical students' growth and development. According to the change of medical education environment, the tension of doctor-patient relationship and the lack of practical ability, we build a set allround , systematic clinical practice teaching system based on practice curriculum teaching , centralized practice teaching, social practice teaching, practice skills assessment and practice skills competition. The research and practice of the system not only promotes teachers' and student's emphasis on the training of clinical practical skills but also improves student's clinical practice skills, strengthen teachers' clinical skills teaching ability, and boost the construction of clinical skills experimental center.

Objective To investigate the effect of G protein?coupled estrogen receptor (GPER) on the diastolic function of renal interlobular artery and reduce renal ischemia?reperfusion injury in rats. Methods Female ovariectomized rats were divided into control group; ischemia?reperfusion injury (IRI) group;GPER?specific agonist (G1) intervention group;GPER?specific blocker+GPER?specific agonist (G15+G1) intervention group. Histopathological examination (HE staining), renal function test and Paller score were used to identify the success of the model and the degree of kidney damage. In vitro microvascular pressure diameter measuring instrument was used to detect the relaxation and contraction activity of renal interlobular artery in each group. Immunofluorescence technique was used to observe the expression of GPER on the renal interlobular artery. Westernblotting was used to detect the expression of GPER protein in renal interlobular artery of rats in each group. The NO content was determined by a nitrate reductase method. Results Compared with IRI group, serum BUN, Scr level and Paller score in G1 intervention group were significantly decreased (all P<0.05). The systolic rate of renal interlobar artery was significantly increased [(40.76 ± 1.57)％ vs (29.78 ± 1.87)％, P<0.05]. The results of immunofluorescence showed that GPER was expressed in renal interlobular artery smooth muscle cells and endothelial cells, and the expression of IRI group was higher than that of the control group. The expression of G15+G1 intervention group was lower than that of G1 intervention group (all P<0.05). Compared with the IRI group, the NO content in the G1 intervention group increased significantly (all P<0.05). Conclusions During renal ischemia ?reperfusion injury, GPER may regulate the systolic and diastolic activity of the renal interlobar artery by increasing the content of NO, so as to alleviate the renal ischemia?reperfusion injury.

Objective To evaluate the effects of remifentanil (RMF)on large conductance cal-cium-activated potassium channel (BKCa)and voltage-gated potassium channel (KV)activition currents in basilar arterial smooth muscle cells (BASMCs)of normotensive and hypertensive rats. Methods Spontaneously hypertensive rats (SHR)and homologous normotensive wistar-kyoto (WKY)rats,were used in this study.BASMCs were obtained freshly by the method of enzymolysis. Six basilar artery smooth muscle cells of each rat were chosen and analyzed.Outward current ampli-tude was recorded by the whole-cell patch clamp technique.The outward current amplitude under all stimulation voltage in set of step stimulation protocol before (basal level)and after administration of RMF (3×10-7mol/L)were recorded respectively and net current was calculated (net current=cur-rent amplitude after administration-basic value).With administration by concentrations cumulative method,the current amplitude under +60 mV stimulation voltage was separately recorded before (basic value)and after application of different concentrations of RMF (10-10,10-9,10-8,10-7, 10-6,10-5mol/L),then calculated current increasing rate and the half effective concentration (EC50)of RMF increasing current amplitude in BASMCs.Another six basilar artery smooth muscle cells of each rat were chosen and given RMF (3×10-7mol/L),and separately treated with BKCa channel blocker (tetraethylammonium,TEA)and Kv channel blocker (4-aminopyridine,4-AP),and then administrated the corresponding RMF mixture.The current amplitude was recorded after each dose.Results At 0,+20,+40 and +60 mV,the net current generated by RMF on both BASMCs of rats was successively and significantly increased (P <0.05).The increment rate of outward currents in BASMCs generated by 10-10,10-9,10-8,10-7RMF successively and significantly went upward (P<0.05).Compared to WKY rats,the half-effective concentration(EC50)of RMF increas-ing the current amplitude in BASMCs of SHR significantly rose(P<0.05).Compared with the base-line,the current amplitude in BASMCs of the two kind rats was significantly increased after adminis-tration of RMF,and decreased after administration of TEA or 4-AP (P<0.05);Compared to ad-ministration of TEA or 4-AP,the current amplitude in BASMCs of the two kind rats was significantly in-creased after administration of TEA+RMF or 4-AP+RMF (P<0.05).Conclusion Bkcaand Kv currents in both BASMCs of SHR and WKY rats were activated by RMF in a voltage-dependent and dose-dependent manner,and the effect of RMF on BKCaand Kvactivition currents in BASMCs of SHR was weaker than WKY rats.

Objective To study the changes of intracellular calcium ion concentration in pulmonary artery smooth muscle cells (PASMCs) of hypoxic-induced persistent pulmonary hypertension (PPH) induced by calcium-sensitive receptor (CaSR) in a newborn mouse model.Method Ninety-six newbom C57BL/6 mice were randomly divided into control group,PPH group,PPH + agonist group and PPH + inhibitor group,with 24 mice in each group.The PPH model was induced by 12％ oxygen for 14 days.In the beginning,intraperitoneal injection of CaSR agonist (GdCl3) and CaSR inhibitor (NPS2390) were performed to mice in PPH + agonist group and PPH + inhibitor group respectively daily.After 14 days of modeling,pulmonary artery smooth muscle cells (PASMCs) of all four groups were cultured in vitro.Changes of Ca2+ fluorescence intensity in PASMCs of the four groups were detected by laser confocal microscope continuously.Result The ratio of pulmonary small vascular wall thickness to the vascular diameter and right ventricle/left ventricular thickness in PPH group were greater than those in the control group [(21.1％ ±1.8％) vs.(27.0％ ±0.9％),(0.62 ±0.22) vs.(0.83±0.45)],the differences were statistically significant (P ＜ 0.05),which imply that PPH mouse model was constructed successfully.The average Ca2+ fluorescence intensity in PASMCs of control group,PPH group,PPH + agonist group and PPH+ antagonist group were 122.5 ± 3.0,2 058.8 ±46.3,2 286.6 ±51.4 and 1 134.8 ± 8.5,respectively.The average Ca2+ fluorescence intensity in PASMCs of the PPH group,PPH + agonist group and PPH + antagonist group was higher than that of the control group respectively,the average Ca2+ fluorescence intensity in PASMCs of PPH group was higher than that of PPH + antagonist group,the differences were statistically significant (P ＜ 0.05).Whereas the difference of average Ca2 + fluorescence intensity in PASMCs of PPH group and PPH + agonist group was of no statistical significance (P ＞ 0.05).Conclusion CaSR may be involved in the occurrence and development of hypoxic-induced PPH in neonatal mice by affecting the intracellular Ca2+ concentration in pulmonary artery smooth muscle cells.