BACKGROUND: Studies have demonstrated that hyperpolarization-activated andcyclic nucleotide-gated cation channels (HCN) 2 and HCN4 are abnormal expressed in ventricular muscle following heart disease, which is closely correlate to ventricular arrhythmia. Bone marrow stem cells (BMSCs) transplantation can improve damaged cardiac muscle; however, its effect on remodeling of ion channel is unclearly. OBJECTIVE: To detect the changes of HCN2 and HCN4 expression in left ventricle following BMSCs transplantation.METHODS: Five Sprague-Dawley (SD) rats, aged 3 weeks, were prepared for BMSCs by Percoll method. Additional 30 health, male, SD rats, were randomly divided into DMEM, cell transplantation, sham operation and control groups. At 4 weeks after model preparation, DMEM culture medium was injected into the infarcted area and surroundings with 5 points in the DMEM group. The 3rd generation of cultured BMSCs (200 μL, with 5×10~6 cells) were injected into rats in the cell transplantation group with the same methods. The mRNA and protein expression of HCN2 and HCN4 gene was detected by RT-PCR and Western blot respectively.RESULTS AND CONCLUSION: In non-infarcted region, the mRNA and protein expression of HCN2 and HCN4 among each groups had no significant difference (P > 0.05). Compared with the control and sham operation groups, mRNA and protein expression of HCN2 and HCN4 in surrounding of the infracted region was elevated in the DMEM group (P < 0.05), which was greater than that of the cell transplantation group (P < 0.05). The mRNA and protein expression of HCN2 and HCN4 was smaller in the center area of infracted region in the DMEM group than that of the control and sham operation groups (P < 0.05), which was similar to the cell transplantation group (P > 0.05). Acute myocardial infarction can increase mRNA and protein expression of HCN2 and HCN4 in infracted region surrounding. BMSCs transplantation may lower the fatality rate of ventricular arrhythmia by reducing HCN2 and HCN4 expression.

Objective To explore the effects of sedationand hemodynamics on different ages patients with the same concentration of dexmedetomidine under general anesthesia.Methods A total of 264 patients (ASAⅠ-Ⅱ)with orthopaedic surgery under general anesthesia in our hospital from April 2013 to May 2015 were divided into 3 groups by age,the young group (group Y,n =76),middle age group (group M, n =107),and old age group (group O,n =81 ).Fifteen minutes before anesthesia,patients were infused dexmedetomidine with 1 μg/kg, maintain the concentration of 0.5 μg·kg-1 ·h-1 and stop at 30 minutes before surgery finished.The SBP、DBP、BIS、HR before anesthesia (T1),pump injection start(T2),tracheal intubation(T3),1 minute after intubation(T4),5 minutes after skin incision(T5),endotracheal ex-tubation(T6)were observed.The dosage of propofoland remifentanil in anesthesia,duration from stop infusion to endotracheal extubation, Ramsay score and adverse reactions 5 minutes after PACU also need to be recorded.Results The level of SBP and DBP were significantly increased at T2,T3 in all groups.Compared with group O,both group Y and group M increased significantly,the difference was statistically significant(P <0.05).The level of SBP and DBP were significantly decreased at T5 in all groups,the difference was statistically significant (P <0.05).There was no significant difference in 3 groups at T4-T6(P >0.05).Compared with T1,the level of HR and BIS were signifi-cantly decreased at T2-T5,the difference was statistically significant(P <0.05).The dosage of propofol and remifentanil in group Y and group Mwas more than that of group O.The extubation time was significantly shorter and the Ramsay score was significantly less than those of the group O,the difference was statistical significance(P <0.05).SAS scores among the three groups was not significant difference (P >0.05). There was no significant difference in the total adverse reaction between group Y and group M(P >0.05),but it was significantly lower than that of group O(P <0.05).Conclusion Dexmedetomidine has good sedative effect in all groups,but older group have more adverse reac-tions and wake up time is extended.The concentratiuon of dexmedetomidine should be adjusted according to the age of patients.

Objective To investigate influence of dexmedetomidine on postoperative cognitive function in elder patients after hip re-placement surgery under spinal anesthesia. Methods Forty elderly patients with ASAⅠ~Ⅲ,undergoing hip replacement with spinal anesth-sia,were randomly divided into dexmedetomidine group( group A) and normal saline group( group B) ,with 20 patients in each group. Dexme-detomidine was given with 1 μg/kg after anesthesia and followed with 0. 5 μg·kg-1 ·h-1 in group A. The equal volume of normal saline was infused in group B. Cognitive function was evaluated before anesthesia,3 and 7 days after surgery by mini-mental state examination( MMSE) . The intraoperative concentration of TNF-α,IL-6,MDA were detected at the time of before surgery(T0),end of surgery(T1),3 days after sur-gery(T2),7 days after suegery. Results There was no significant difference in MMSE score before anesthesia between the two groups (P>0. 05). The difference of MMSE score at postoperative 3 days between two groups was statistical significance (P<0. 05). The MMSE score recovered normal in both groups 7 days later. There was no significant difference of TNF-α,IL-6,MDA concentration at T0 between two groups(P>0. 05). Compared with T0,the concentration of TNF-α,IL-6,MDA at T1,T2 in group B increased,the difference was significant. And the concentration of IL-6 at T1 in group A decreased,compared with that at T0,the difference was significant(P<0. 05). The concentra-tion of TNF-α,IL-6 at T1,T2 and MDA at T2 in group A were lower than those in group B,the difference was significant. (P<0. 05). Con-clusion Dexmedetomidine can decreased the concentration of TNF-α,IL-6,MDA,and improve the postoperative cognitive dysfunction of eld-erly patients who finished the hip replacement surgery under spinal anesthesia.

Objective: To investigate the effects of Ala-Gln induced heat shock protein 70 (HSP70) expression on myocardial ifbrosis and connexin43 (Cx43) remodeling in experimental rats’ model.
Methods: A total of 32 SPF male SD rats were randomly divided into 4 groups:①Control group,②Model group, the rats received isoprenaline (ISO) 5m/(kg·d),③Intervention group, the rats received ISO+Ala-Gln 0.75mg/(kg·d),④Quercetin group, the rats received ISO+quercetin 100mg/(kg·d)+Ala-Gln+DMSO. n=8 in each group. All animals were treated for 7 days and killed in 4 weeks for relevant examinations. HE and Masson staining was conducted to observe myocardial ifbrosis, then calculate collagen volume fraction; immunohistochemistry was applied to measure myocardial HSP70 expression,
extracellular signal regulated kinase (p-ERK1/2) and Cx43 distribution, then conduct semi-quantitative analysis by speciifc soft ware.
Results: HE and Masson staining indicated that Control group had no obvious myocardial ifbrosis, Model group and Quercetin group had obvious ifbrosis, and Intervention group showed less ifbrosis than the other 2 groups, all P<0.01. The fibrosis level was similar between Intervention group and Control group, P>0.05. The myocardial HSP70 expression was similar among Control, Model and Quercetin groups, P>0.05, while HSP70 expression was signiifcantly higher in Intervention group than the other 3 groups, all P<0.01. The myocardial p-ERK1/2 level was lower in Intervention group than Model and Quercetin groups, all P<0.01. The myocardial Cx43 level was similar between Control group and Intervention group with linear distribution, while it was higher in Intervention group than Model and Quercetin groups with disordered distribution, all P<0.01.
Conclusion: Ala-Gln inducing the higher expression of HSP70, which may reduce myocardial ifbrosis in experimental rats, it could be because of HSP70 down regulating p-ERK1/2 expression and inhibiting ERK signaling pathway.

Objective To compare and analyze the clinical application of lumbar plexus combined with sciatic nerve block and spinal anesthesia for elderly patients with knee joint surgery.Methods A total of 77 elderly patients with ASAⅠ ~Ⅲ undergoing single knee re-placement surgery were randomly divided into combined group which recieved lumbar plexus combined with sciatic nerve block and spinal an-esthesia group.The baseline values,blood pressure and heart rate at multiple time points,the block area and duration,the volume of intraoper-ative fluid,and other indexes of adverse reaction were observed.Results The MAP,SBP and DBP in the spinal anesthesia group after the op-eration have changed significantly at the time of T1,T2 and T3.The operating of anesthesia in the combined group was shorter than that of spi-nal anesthesia group.The rate of adverse reactions in combined group was significantly lower than that inspinal anesthesia group.Conclusion The spinal anesthesia can be satisfied for operation requirements,but it will cause the unstable circulation and varied adverse reactions.Lum-bar plexus combined with sciatic nerve block is safe and effective with less adverse reactions,less disturbance of hemodynamics,which is much better for the old or the patients with coagulation abnormalities combined heart and lung disease.

Objective To evaluate the efficiency of dezocine combined with sufentanil on postoertive analgesia for spinal deformity sur-gery.Methods Divided the 90 patients who were admitted into our hospital from January 2013 to September 2015 into three groups by ran-dom single blind method,namely the dezocine group,the sufentanil group and the combined group,with 30 cases in each group.All the pa-tients underwnet propofol and sevoflurane static absorption compound anesthesia,and they were given continuous intravenous analgesia with different drugs after the surgery.Their visual analogue scale (VAS)score,sedation scale (SS)score,adverse reaction,total PCIA times,ef-fective PCIA times,respiratory rate and arterial blood gas were measured at 2,6,24,48 hours after operation.Results The VAS score of the combined group was lower than that of the dezocine group (P <0.05).The combined group was significantly superior to the dezocine group and the sufentanil group in SS score and adverse reactions.At 24 and 48 hours after surgery,SaO2 and PaO2 in the combined group were higher than those in sufentanil group (P <0.05).PaCO2 in the combined group was lower than that in the dezocine group and the sufentanil group(P <0.05).Conclusion Dezocine combined with sufentanil is a more efficiency way with less adverse reaction on postoperative anal-gesia for spinal deformity surgery,and it is an ideal way of analgesia.

Objective To investigate the expression of neural-nitric oxide synthase (nNOS) in renal clear cell carcinoma and its clinical significance.Methods The expression of nNOS mRNA in 533 samples of TCGA database was analyzed with Student t test,and statistical analysis was performed to assess the relationship between nNOS expression and clinical prognosis with Kapla-Meier test.Western blot analysis of nNOS protein expression in 10 cases of clear cell renal cell carcinoma(ccRCC) from department of urology of Wuhan union hospital with student t test.Results The mRNA levels of nNOS in 72 cases of ccRCC in tumor tissues and adjacent tissues and were 2.99 ± 0.28 and-1.57 ± 0.17,it is significantly lower than those in adjacent tissues (P ＜ 0.01).The mRNA levels of nNOS in 533 cases of ccRCC,in tumor tissues and adjacent tissues and were 2.99 ± 0.28 and-1.76 ± 0.05,it is significantly lower than those in adjacent tissues (P ＜ 0.01).A total of 533 sample studies showed a low correlation between nNOS expression and clinical T stage,T1-1.59 ±0.08,T2-1.96 ±0.13,T3-1.90 ±0.09,T4-2.38 ±0.28 (P =0.0029) and -1.63 ±0.06 and-2.16 ± 0.13 between non-metastasis and no-metastasis (P =0.0009),and-1.57 ± 0.08 and-2.03 ± 0.11 between non-recurrence and recurrence (P =0.008).Survival analysis showed that the overall survival time were (40.3 ± 5.6) months and (48.3 ± 5.7) months in lower and higher nNOS expression,and disease free survival time were (37.1 ± 2.1) months and (40.3 ± 5.6) months in lower and higher nNOS expression,both with shorter time in low expression of nNOS (P ＜ 0.01).nNOS proteins were 1.02 ± 0.16 and 0.61 ± 0.1 1 in tumor tissues and adjacent tissues with significantly lower expression(P＜0.05).Conclusions The mRNA and protein of nNOS are lower in ccRCC with a poor prognosis of ccRCC.

Objective To observe the effects of propofol on neural stem ceils in mouse developing hippocampal dentate gyrus (DG).Methods Healthy 7 d old mice from the same litters were randomly allocated into three groups:high dose propofol group,low dose propofol group and 10％ fat emulsion control group.All mice were treated with drugs on postnatal 7 d.The mice in high dose propofol group were intraperitoneally injected with 60 mg/kg propofol;the mice in low dose group were intraperitoneally injected 30 mg/kg propofol;while the mice in the control group with equivalent volume of 10％ fat emulsion.Some mice were sacrificed at 24 h after medication injection,and the others were sacrificed at postnatal 14 d.The morphology and expression levels of Ki67,Nestin,BLBP and NeuN in hippocampal DG were detected by immunohistochemical method.Results Healthy 7 d old mice from the same litters were randomly allocated into three groups:high dose propofol group,low dose propofol group and 10％ fat emulsion control group.All mice were treated with drugs on postnatal 7 d.The mice in high dose propofol group were intraperitoneally injected with 60 mg/kg propofol;the mice in low dose group were intraperitoneally injected 30 mg/kg propofol;while the mice in the control group with equivalent volume of 10％ fat emulsion.Some mice were sacrificed at 24 h after medication injection,and the others were sacrificed at postnatal 14 d.The morphology and expression levels of Ki67,Nestin,BLBP and NeuN in hippocampal DG were detected by immunohistochemical method.Conclusion High dose propofol inhibits the proliferation of neural stem cells in hippocampal DG,and impaired the prominence number of neural stem cells and causes neurons dysmaturity.

Objective: To explore the molecular mechanism of Taoren-Honghua herb pair (THP) on syndrome of bloodstasis based on the network pharmacology. Methods: We collected THP's compounds from traditional Chinese Medicinedatabases and input them into Pharm Mapper to get their potential targets, and collected the known targets of compoundsby Scifinder. Then we did KEGG-pathway analysis by DAVID database. Finally draw and analyze the network byCytoscape by information above. Results: Seventeen compounds of THP acquired 74 known targets, which was associatedwith four modules: improving the hemodynamics, anticoagulation, anti-inflammation, regulating apoptosis andproliferation. We also got 317 potential targets through PharmMapper and got 128 signaling pathway through pathwayenrichment including 39 disease-related pathways, 25 endocrine-related pathways, 11 immune-related pathways and soon. Conclusion: The four modules of the known target are exactly related to the four characteristics of the syndrome ofblood stasis. The potential targets and the 128 signal pathways involve a variety of pathophysiological processes of thesyndrome of blood stasis. These reflect the molecular mechanism of THP intervention in the syndrome of blood stasis

Objective:Multidrug-resistant tuberculosis(MDR-TB)has a high mortality and is always one of the major challenges in global TB prevention and control.Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients.For follow-up data,the Cox proportional hazards regression model is an important multifactor analysis method.However,the method has significant limitations in its application,such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model.Therefore,Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy,and compare the differences between these 2 methods in their application. Methods:Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1,2017 to March 31,2021.Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors.Conventional and Bayesian Cox regression models were established to estimate the hazard ratios(HR)and their 95% confidence interval(95% CI)for the factors affecting the death of MDR-TB patients.The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable.The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. Results:The median survival time(1st quartile,3rd quartile)of the 388 MDR-TB patients included in the study was 10.18(4.26,18.13)months,with the longest survival time of 31.90 months.Among these patients,a total of 12 individuals died of MDR-TB and the mortality was 3.1%.The median survival time(1st quartile,3rd quartile)for the deceased patients was 4.78(2.63,6.93)months.The majority of deceased patients,accounting for 50%,experienced death within the first 5 months of anti-TB therapy,with the last mortality case occurring within the 13th month of therapy.The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications(HR=6.96,95% CI 2.00 to 24.24,P=0.002)and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up(HR=0.19,95% CI 0.05 to 0.77,P=0.020).In the results of Bayesian Cox regression model,the iterative history plot and Blue/Green/Red(BGR)plot for each parameter showed the good model convergence,and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture(HR=0.33,95% CI 0.08 to 0.87).Additionally,compared to patients without complications,those with comorbidities had an approximately 6.80-fold increase in the risk of death(HR=7.80,95% CI 1.90 to 21.91).Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up(HR=0.10,95% CI 0.01 to 0.30).The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model,except for parameter standard deviations of receiving regular follow-up(Bayesian model was 0.77;conventional model was 0.72)and pulmonary cavities(Bayesian model was 0.73;conventional model was 0.73). Conclusion:The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients.Complications are the main risk factors of death in MDR-TB patients,while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death.For data with a small sample size and low incidence of outcome,the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.