Objective To investigate the protective effect of valeric acid on Doxorubicin-induced myocardial injury in mice.Methods C57BL/6J mice and AC16 cells were randomly divided into control group,injury group,and low-,medium-,and high-dose valeric acid groups.Doxorubicin was used to treat mice and myocardial cells to establish myocardial injury models.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes of myocardial tissue in mice,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of myocardial injury markers and inflammatory factors in mice from each group.Cell counting kit was used to detect the viability of myocardial cells in each group,and spectrophotometry was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the serum and myocardial cells in mice from each group.Reactive oxygen species(ROS)fluorescence probe was used to detect the levels of reactive oxygen species in each group,and flow cytometry was used to detect the apoptosis rate of each group.Western blot was used to detect the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)proteins in myocardial tissue and myocardial cells of mice from each group.Results Compared with the injury group,the myocardial injury in the low-,medium-,and high-dose valeric acid groups was ameliorated,the levels of myocardial injury markers gradually decreased,the levels of SOD in the body,and the expression levels of Nrf2 and HO-1 proteins gradually increased,and the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Compared with myocardial cells in the injury group,the viability of myocardial cells,the levels of SOD,and the expression levels of Nrf2 and HO-1 proteins in the low-,medium-,and high-dose valeric acid groups gradually increased,while the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Conclusion Valeric acid can inhibit inflammation and oxidative stress to improve Doxorubicin-induced myocardial injury,which may be related to the activation of Nrf2/HO-1 signaling pathway by valeric acid.

Objective:To evaluate the effects of different doses of sufentanil on the pupillary dilation reflex (PDR) during induction of general anesthesia.Methods:In this randomized controlled study, 124 patients of either sex, aged 18-64 yr, with a body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing surgery with general anesthesia, were divided into 4 groups ( n=31 each) using a random number table method: control group (group C) and different doses of sufentanil groups (S1-S3 groups). Sufentanil 0.2, 0.4 and 0.6 μg/kg were intravenously injected in S1-S3 groups, respectively, and the equal volume of normal saline was injected instead in group C. Tetanic stimulation (50 mA, 50 Hz, 5 s) was applied at 5 min after injection of sufentanil. Pupil diameter was measured and the pupillary dilation value and dilation rate were calculated upon entering the operating room while awake, after loss of consciousness, 5 min after intravenous injection of sufentanil, and at maximal pupil diameter after tetanic stimulation. The presence or absence of PDR, PDR latency and PDR duration were also recorded. Results:The pupillary dilation values and dilation rates decreased progressively from group C through groups S1 to S3 ( P<0.05). Compared to group C, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in groups S2 and S3, and the duration of PDR was significantly shortened in groups S1-S3 ( P<0.05). Compared to group S1, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in S2 and S3 groups ( P<0.05). Conclusions:The inhibitory effect of sufentanil on the PDR during induction of general anesthesia is dose-dependent.

Objective:To evaluate the effects of different doses of sufentanil on the pupillary dilation reflex (PDR) during induction of general anesthesia.Methods:In this randomized controlled study, 124 patients of either sex, aged 18-64 yr, with a body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing surgery with general anesthesia, were divided into 4 groups ( n=31 each) using a random number table method: control group (group C) and different doses of sufentanil groups (S1-S3 groups). Sufentanil 0.2, 0.4 and 0.6 μg/kg were intravenously injected in S1-S3 groups, respectively, and the equal volume of normal saline was injected instead in group C. Tetanic stimulation (50 mA, 50 Hz, 5 s) was applied at 5 min after injection of sufentanil. Pupil diameter was measured and the pupillary dilation value and dilation rate were calculated upon entering the operating room while awake, after loss of consciousness, 5 min after intravenous injection of sufentanil, and at maximal pupil diameter after tetanic stimulation. The presence or absence of PDR, PDR latency and PDR duration were also recorded. Results:The pupillary dilation values and dilation rates decreased progressively from group C through groups S1 to S3 ( P<0.05). Compared to group C, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in groups S2 and S3, and the duration of PDR was significantly shortened in groups S1-S3 ( P<0.05). Compared to group S1, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in S2 and S3 groups ( P<0.05). Conclusions:The inhibitory effect of sufentanil on the PDR during induction of general anesthesia is dose-dependent.

Objective To investigate the protective effect of valeric acid on Doxorubicin-induced myocardial injury in mice.Methods C57BL/6J mice and AC16 cells were randomly divided into control group,injury group,and low-,medium-,and high-dose valeric acid groups.Doxorubicin was used to treat mice and myocardial cells to establish myocardial injury models.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes of myocardial tissue in mice,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of myocardial injury markers and inflammatory factors in mice from each group.Cell counting kit was used to detect the viability of myocardial cells in each group,and spectrophotometry was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the serum and myocardial cells in mice from each group.Reactive oxygen species(ROS)fluorescence probe was used to detect the levels of reactive oxygen species in each group,and flow cytometry was used to detect the apoptosis rate of each group.Western blot was used to detect the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)proteins in myocardial tissue and myocardial cells of mice from each group.Results Compared with the injury group,the myocardial injury in the low-,medium-,and high-dose valeric acid groups was ameliorated,the levels of myocardial injury markers gradually decreased,the levels of SOD in the body,and the expression levels of Nrf2 and HO-1 proteins gradually increased,and the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Compared with myocardial cells in the injury group,the viability of myocardial cells,the levels of SOD,and the expression levels of Nrf2 and HO-1 proteins in the low-,medium-,and high-dose valeric acid groups gradually increased,while the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Conclusion Valeric acid can inhibit inflammation and oxidative stress to improve Doxorubicin-induced myocardial injury,which may be related to the activation of Nrf2/HO-1 signaling pathway by valeric acid.

Objective To investigate the effect of ultrasound-guided stellate ganglion block(SGB)on intraoperative fentanyl dosage in the patients undergoing open thyroidectomy.Methods A total of 70 patients with elective open thyroidectomy under general anesthesia in the Affiliated Hospital of North Sichuan Medical College from November 2021 to April 2022 were selected as the study subjects and divided into the SGB group(group S,n=35)and the control group(group C,n=33).The group S conducted ultrasound-guided SGB at 15 min before anesthetic induction(injection of 0.25％marcaine 6-8 mL),and group C conducted the stellate ganglion recognition under the ultrasound guidance in 15 min before anesthetic induction without conducting other operations.All patients all received the anesthesia induction and maintenance under the same BIS moni-toring.The fentanyl dosage,recovery time,anesthetic drugs dosage,fluid infusion amounts,bleeding volume,use rate of atropine and ephedrine,operation time and postoperative complications as well as the VAS scores in PACU 30 min,at postoperative 3,6,12,24 h were recorded.Results Compared with group C,the intraopera-tive amount of fentanyl in group S was significantly decreased[(247.9±65.4)μg vs.(295.7±61.5)μg,P=0.003].The propofol dosage,cisatracurium dosage,fluid infusion amounts,bleeding amounts,use rate of atro-pine and ephedrine,recovery time and incidence rate of complications had no statistical differences between the two groups(P＞0.05).The VAS scores at various time points in group S all were lower than those in group C(P＜0.05).Conclusion Ultrasound-guided SGB could reduce the fentanyl use amounts during operation in the patients with open thyroidectomy.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

Objective:To evaluate the effect of propofol and remifentanil in different target-controlled infusion(TCI) sequences on hypotension during induction of general anesthesia in hypertensive patients.Methods:A total of 132 patients with hypertension of both sexes, aged 50-75 yr, of American Society of Anesthesiologists Physical Status classificationⅡ or Ⅲ, with body mass index of 18-30 kg/m 2, scheduled for elective tracheal intubation under general anesthesia, were divided into 3 groups( n=44 each) using a random number table method: group C, PR group and RP group. In group C, propofol(target effect-site concentration 5 μg/ml) and remifentanil(target effect-site concentration 5 ng/ml) were simultaneously given by TCI. Propofol was given by TCI followed by TCI of remifentanil in PR group. Remifentanil was given by TCI followed by TCI of propofol in RP group. The development of hypotension was observed within 10 min after induction of general anesthesia, and the consumption of propofol, remifentanil and ephedrine, time of loss of consciousness, time of tracheal intubation and adverse reactions during the perioperative period were recorded. Results:Compared with group C, the incidence of hypotension during induction was significantly decreased, the consumption of propofol and ephedrine was decreased, and the BIS value was increased when consciousness disappeared, the time of loss of consciousness and time of tracheal intubation were prolonged, the BIS value was increased at loss of consciousness in PR group, and the consumption of ephedrine was significantly decreased, and the time of loss of consciousness and time of tracheal intubation were prolonged in RP group( P<0.05). Compared with PR group, the consumption of ephedrine was significantly decreased, and the time of loss of consciousness was prolonged in RP group( P<0.05). There was no significant difference in the incidence of responses to tracheal intubation, injection pain, bucking, inhibition ratio, postoperative delirium, postoperative nausea and vomiting, and intraoperative awareness during induction among the three groups( P>0.05). Conclusions:TCI of remifentanil followed by TCI of propofol can decrease the development of hypotension during induction of general anesthesia in hypertensive patients.

Objective:To compare the efficacy of individualized PEEP determined by lung electrical impedance tomography (EIT) and dynamic lung compliance (Cdyn) during lung-protective ventilation strategies in the patients undergoing general anesthesia.Methods:Sixty patients of both sexes, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18.5-28.0 kg/m 2, undergoing elective surgery with general anesthesia and endotracheal intubation in the Second Affiliated Hospital of Soochow University, were selected.Lung-protective ventilation strategy was applied in supine position after general anesthesia.The peak value of PEEP did not exceed 10 cmH 2O, with an increment/decrement of 2 cmH 2O for titration.The corresponding Cdyn value and lung EIT data were collected during titration.The patients were divided into 2 groups ( n=30 each) using a random number table method: titration first increased and then decreased group (group A) and titration first decreased and then increased group (group B). The determination method of individualized PEEP: Cdyn method was the PEEP corresponding to the maximum Cdyn value; EIT method was obtained through PV500 PC software analysis.The level and success rate of individualized PEEP determined by the Cdyn and EIT methods were compared, and the ICC consistency analysis of the determined individualized PEEP was performed. Results:Compared with the Cdyn method, the success rate of individualized PEEP determined by EIT method was significantly increased, and the level of individualized PEEP was decreased in the two group ( P<0.05). In group A, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.761, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.763, P<0.05). In group B, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.809, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.797, P<0.05). Conclusion:The agreement between the individualized PEEP determined by lung EIT method and Cdyn method during lung-protective ventilation is good in the patients undergoing general anesthesia, and the success rate of EIT method is higher, and the level of individualized PEEP is lower.

Objective To determine the optimal positive end-expiratory pressure (PEEP) for volume-controlled ventilation using pulmonary electrical impedance tomography in the patients undergoing surgery with general anesthesia.Methods Fifty patients of both sexes,aged 18-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,with body mass index of 18.5-28.0 kg/m2,scheduled for surgery for ureteral calculi under general anesthesia,were enrolled in this study.The patients were tracheally intubated after anesthesia induction and mechanically ventilated in volume-controlled mode,with tidal volume 6 ml/kg,mean arterial pressure was recorded at 3 min of ventilation and served as the baseline value,and then PEEP was increased with an increment of 3 cmH2O every 3 min until PEEP reached 15 cmH2 O.The percentage of dorsal pulmonary ventilation and peak airway pressure were recorded at 3 min of ventilation with different PEEPs.When the decrease in mean arterial pressure was more than 20％ of the baseline value during ventilation,deoxyepinephrine 0.1 mg was injected intravenously,and the consumption of deoxyepinephrine was recorded within 3 min of ventilation with different PEEPs.Results Peak airway pressure was gradually increased with the increase of PEEP (P＜0.05),the percentage of dorsal pulmonary ventilation was gradually increased when PEEP was 6 cmH2O (P＜ 0.05),and the consumption of deoxyepinephrine was gradually increased when PEEP was 15 cmH2O (P＜0.05).Conclusion The optimal PEEP is 12 cmH2O during volume-controlled ventilation with tidal volume of 6 ml/kg in the patients undergoing surgery with general anesthesia.

Objective To explore the genetic mutation spectrum of patients with hypertrophic cardiomyopathy (HCM) and analysis the correlation of genotype phenotype.Methods Collect peripheral venous blood of the 51 cases unrelated HCM patients(35 male and 16 female) in the Beijing Anzhen Hospital of Capital Medical University from 2013 to 2016.Sequence whole exons of human and analysis seven major mutations of HCM including:MYBPC3、MYH7 、TNNT2、TNNI3 、MYL2 、TPM1 and ACTC1.Then compare the results with clinical characteristics.Results 24 patients(47.1％) had 22 kinds of pathogenicity or possibly pathogenicity mutations.The 90.9％ (20/22) of mutations only occurred one time,except MYH7 gene's 663 amino acid and the TNND gene's 157 amino acid which had twice.The mutations of MYBPC3,MYH7,TNNT2,TNNI3,MYL2,TPM1 and ACTC1 accounted for 45.8％ (11/24),20.8％ (5/24),12.5％ (3/24),8.3％ (2/24),8.3％ (2/24),4.2％ (1/24),and 0 respectively.No amphimutation had been found that causes illness or possibly.Through the comparison of clinical features between Genotype positive(24 cases) and negative(27 cases) patients:the incidence of syncope(19.6％ vs.7.8％,P ＜ 0.05),the largest left ventricular wall thickness[(22.8 ± 2.6) mm vs.(20.0 ± 3.4) mm,P ＜ 0.05],family history of HCM(20.8％ vs.0,P ＜0.05),percentage of apical hypertrophy(25.5％ vs.11.8％,P ＜ 0.05);The ratio of left ventricular outflow tract obstruction in MYH7 group was higher than MYBPC3 group (80.0％ vs.18.2％,P ＜ 0.05).Conclusion MYBPC3 is the most common mutation gene in HCM patients.Phenotype is more severe in geuotype positive patients than in genotype negative patients.Relationship between specific gene mutations and clinical phenotype requires further study.