Objective:To explore the mechanism of Honghua Xiaoyao Tablets in the treatment of premature ovarian failure (POF) using network pharmacology and molecular docking technology; To conduct further experimental verification.Methods:The active components and related targets of Honghua Xiaoyao Tablets were obtained using TCMSP and PubChem databases, and the related targets of POF were obtained by using GeneCards database. The Venn online tool was used to screen the intersection genes, and the STRING database was used to construct the PPI network. Then, GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersecting genes through the Metescape database, and Cytoscape 3.7.1 software was used to construct the "active component-target" network and "Chinese materia medica-active component-target-key pathway-disease" network. Finally, molecular docking verification was carried out. Mice were divided into blank group, model group, and Honghua Xiaoyao Tablets group using a random number table method, with 8 mice in each group. Except for the blank group, mice in each group were treated with zona pellucida polypeptide 3 (ZP3) and Freund's Complete Adjuvant (FCA) to establish a mouse model of immune POF. Mice in the Honghua Xiaoyao Tablets group received Honghua Xiaoyao Tablets solution 0.56 g/kg for gavage, and the blank control group and the model group received saline for gavage for consecutive 4 weeks. The histopathological changes of the mouse ovary were observed by HE staining. Immunohistochemical staining was used to observe the expression of ESR1, and Western blot was used to detect the expressions of Akt and p-Akt.Results:A total of 80 intersection targets between Honghua Xiaoyao Tablets and POF were obtained, and the PPI network contained 44 core targets. The top 5 compounds in the topological analysis were formononetin, quercetin, Betulinic acid, Hydroxysafflor Yellow A and Baicalin, and the top 5 targets were PPARG, ESR1, AR, AKT1 and IL6. The molecular function of core genes was mainly receptor ligand activity, and its biological process mainly involved the positive regulation of cell migration. The cellular components mainly included membrane rafts, which were involved in signaling pathways such as cancer signaling pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. "Chinese materia medica-component-target-pathway-disease" network showed that 8 kinds of Chinese materia medica in the Honghua Xiaoyao Tablets had important core components, among which Glycyrrhizae Radix et Rhizoma and Carthami Flos involved the most important core components. Molecular docking results showed that the active components had a good affinity with the core target. The experimental verification confirmed that Honghua Xiaoyao Tablets promoted follicular development, increased the expression of ESR1 in ovarian tissues and up-regulated the expression level of the key factor of Akt phosphorylation in the PI3K-Akt signaling pathway.Conclusions:The various active components of Honghua Xiaoyao Tablets may act on PPARG, ESR1 and other targets through multiple signaling pathways such as PI3K-Akt and HIF-1 to treat POF. The potential active components are mainly formononetin, quercetin, etc.

Objective:To investigate the effects of dexmedetomidine on the myocardial electrical conduction velocity and the expression and distribution of connexin 43 (Cx43) in rats.Methods:Healthy adult Sprague-Dawley rats of both sexes, weighing 270-330 g, were used.Twelve isolated rat hearts successfully perfused in the Langendorff apparatus were divided into 2 groups ( n=6 each) using a random number table method: control group (group C) and dexmedetomidine group (group D). The hearts were perfused for 15 min with K-H solution, and then the hearts were continuously perfused for 30 min with 37 ℃ K-H solution in group C and with K-H solution containing dexmedetomidine 50 ng/ml in group D. Programmed electrical stimulation was performed after the end of perfusion, the activation latency was recorded, and the electrical conduction velocity of myocardial tissues was calculated, and then the left ventricular myocardial tissues were obtained for determination of the expression and distribution of myocardial Cx43 protein by immunohistochemistry method. Results:Compared with group C, the activation latency was significantly prolonged, the electrical conduction velocity was reduced, and the expression of Cx43 was down-regulated in group D ( P<0.05). Cx43 protein was mostly distributed in intercalated discs at both ends of cells in group C, and there was a tendency for the proteins localized at end-to-end contact sites of ventricular cardiomyocytes to localize at side-to-side contact sites, and the distribution was messy in group D. Conclusions:Dexmedetomidine causes arrhythmia probably through down-regulating the expression of Cx43 protein, changing its distribution, and reducing myocardial electrical conduction velocity in rats.

Objective:To analyze the correlation between obstructive sleep apnea (OSA) and attention deficit hyperactivity disorder (ADHD).Methods:The clinical Data, polysomnography (PSG) and cognitive function examination results of 112 OSA children admitted to Department of Otorhinolaryngology Head and Neck Surgery of the Second Affiliated Hospital of Xi′an Jiaotong University from January 2019 to June 2020 were retrospectively analyzed. According to the severity of OSA, the children were divided into mild, moderate and severe OSA groups, and the basic demographic characteristics, sleep parameters and ADHD occurrence were analyzed. According to the results of ADHD examination, the children were divided into ADHD group and non-ADHD group, and the basic demographic characteristics and sleep parameters were analyzed. Taking these parameters as independent variables, binary Logistic regression analysis was conducted to establish the model equation for predicting the risk of OSA associated ADHD among children.Results:Grouped by OSA severity, among the three groups, apnea-hypopnea index (AHI) [3.70 (2.84, 5.47) vs 8.59 (7.50, 9.54) vs 19.48 (15.83, 25.23)], obstructive apnea index (OAI) [1.31 (0.93, 1.82) vs 3.03 (1.54, 4.41) vs 11.69 (8.53, 15.42)], obstructive apnea-hypopnea index (OAHI) [2.82 (1.81, 3.64) vs 6.17 (5.58, 7.26) vs 15.68 (13.12, 21.25)], and respiratory event-related arousal index [0.50 (0.25, 1.05) vs 1.25 (0.70, 2.23) vs 2.40 (1.60, 4.70)] increased, minimum pulse oxygen saturation (SpO 2) [90.00 (88.00, 92.00) vs 87.00 (83.00, 90.25) vs 81.00 (76.00, 85.00)] decreased, the differences were statistically significant (all P<0.05). The non-rapid eye movement (NREM)1 period time ratio of the severe OSA group was significantly longer than that of the mild OSA group, while the average SpO 2 was significantly lower than that of the mild OSA group; the NREM3 period time ratio of the moderate and severe OSA group was significantly less than that of the mild OSA group; the arousal index of the severe OSA group was significantly greater than the mild or moderate OSA group. There were no statistically significant differences among the three groups in gender, age, body mass index, sleep efficiency, rapid eye movement (REM) period time ratio, and NREM2 period time ratio (all P>0.05). Mild OSA group had 10 cases of ADHD (17.54%), moderate OSA group had 7 cases (23.33%) of ADHD, severe OSA group had 9 cases of ADHD (36.00%), and the difference was not statistically significant. Grouped by ADHD examination, the AHI, OAI, OAHI, and NREM1 period time ratios of the ADHD group were significantly higher than those of the non-ADHD group, while the sleep efficiency, minimum SpO 2 and NREM3 period time ratio were significantly lower than those of the non-ADHD group. The Logistic regression analysis suggested that ADHD was correlated with sleep efficiency, minimum SpO 2, and NREM3 period time.The established Logistic regression equation was: X=15.670+0.061×(sleep efficiency)-0.212×(minimum SpO 2)-0.144×(NREM3 period time ratio), the sensitivity and specificity of the model prediction were 84.6% and 79.1% respectively when the area under the receiveroperating characteristic curves was 0.867. Conclusions:OSA and ADHD in children have a certain correlation. Sleep structure disturbance and intermittent hypoxia may be important reasons. The predictive model equations obtained by PSG in this study can be used to assess the risk of ADHD in children with OSA.

Objective:to investigate the efficacy of drugs in the treatment of laryngeal granuloma after hypothermic plasma radiofrequency surgery in early glottic carcinoma.Methods:Thirty-two cases of laryngeal granulomacoming from 289 patients with early glottic carcinoma treated by plasma radiofrequency surgery under endoscope-supported laryngoscopefrom January 2011 to January 2021 in Dalian Municipal Central Hospital were enrolled. All patients were given oral treatment of zinc gluconate tablets (70 grams per tablet, containing 10 grams of zinc). The usage was 3 tablets each time, twice a day. If the granulation was located in the vocal cord, 20 mg of esomeprazolec was added twice a day, and taken orally on an empty stomach. The total course of treatment was 6-12 weeks.Results:Follow-up and reexamination of electronic laryngoscope showed that the granulation of all patients began to become smaller after 3 weeks of drug treatment and gradually disappeared after 6-12 weeks. After the granulation disappeared, the drug was stopped, and there was no recurrence.Two patients developed nausea and epigastric discomfort after oral administration of zinc gluconate tablets for 3 weeks, and the discomfort disappeared after reducing the dose.Conclusions:Oral administration of zinc gluconate tablets alone or in combination with esomeprazoleis an effective, safe and low recurrence method for laryngeal granuloma after hypothermic plasma radiofrequency ablation in early glottic carcinoma.

Objective To evaluate the role of sarcolemmal ATP-sensitive potassium ( sarcKATP ) channel in sevoflurane-induced maintenance of electrophysiological stability of ventricular myocardium in di-abetic rats. Methods Clean-grade healthy male Sprague-Dawley rats, aged 3 months, weighing 280-320 g, in which diabetes mellitus ( DM) was induced by intraperitoneal streptozotocin 60 mg/kg and confirmed by blood glucose ≥16. 7 mmol/L, were used in this study. Their hearts were excised after anesthesia and retrogradely perfused in a Langendorff apparatus at 4 weeks after establishing the DM model. Twenty-four Langendorff-perfused hearts were divided into 3 groups ( n=8 each) using a random number table method:DM group ( group D) , DM plus sevoflurane group ( group DS) and DM plus sevoflurane plus HMR-1098 group (group DSH). Another 8 Langendorff-perfused hearts of normal rats were selected as control group ( group C) . Hearts were perfused with 37℃ K-H solution via the aorta in each group, 15 min of equilibra-tion later hearts were continuously perfused for 30 min with K-H solution in C and D groups, with K-H solu-tion saturated with 2. 5％ sevoflurane in group DS, or with K-H solution saturated with 10 μmol/L HMR-1098 and 2. 5％ sevoflurane in group DSH. Monophasic action potential (MAP) duration at 50％ and 90％repolarization ( MAPD50 and MAPD90 ) in the endocardium and epicardium of the left ventricular anterior wall were recorded at 15 min of equilibration ( T0 ) and 15 and 30 min of reperfusion ( T1,2 ) , transmural dispersion of repolarization ( TDR) was calculated. S1S2 program-controlled stimulation was performed at the end of perfusion to record the effective refractory period (ERP), ventricular arrhythmia (VA) induced and the longest pacing cycle length ( PCL) of ventricular fibrillation threshold ( VFT) induced. ERP/MAPD90 ratio was calculated. Results Compared with group C, TDR was significantly increased at T0 , ERP/MADP90 ratio was decreased, the incidence of VA induced was increased, and the longest PCL of VFT induced was prolonged in group D ( P＜0. 05) . Compared with group D, TDR was significantly decreased at T2 in group DS (P＜0. 05), and ERP/MADP90 ratio was significantly increased, the incidence of VA in-duced was decreased, and the longest PCL of VFT induced was shortened in DS and DSH groups ( P＜0. 05). TDR was significantly smaller at T2 in group DSH than in group DS (P＜0. 05). Conclusion sarcKATP channel is involved in sevoflurane-induced maintenance of electrophysiological stability of ventricu-lar myocardium in diabetic rats.

Objective To systematically evaluate the effect of intranasal dexmedetomidine on agita-tion during emergence from general anesthesia with sevoflurane in pediatric patients. Methods Pubmed, Embase, The Cochrane Library, China National Knowledge Infrastructure, VIP, Wan-Fang databases were searched for randomized controlled trials involving the effect of intranasal dexmedetomidine on agitation during emergence from general anesthesia with sevoflurane in pediatric patients from the start of their data-base until June 2017, and the reference lists of all included studies were checked manually. Data were ex-tracted independently by two reviewers, and primary evaluation indexes included the incidence of emergence agitation and sedation score. Secondary evaluation indexes included emergence time, extubation time, du-ration of post-anesthesia care unit stay, postoperative consumption of analgesics, incidence of adverse reac-tions ( such as bradycardia, nausea and vomiting, pruritus, laryngeal spasm) during recovery from anes-thesia. The quality of methodology of included studies was assessed. Meta-analysis was conducted with Rev-Man 5. 3 software. Results Eight randomized controlled trials involving 520 pediatric patients were includ-ed in this meta-analysis. Compared with placebo group, the incidence of emergence agitation was signifi-cantly decreased, sedation score was increased, extubation time was prolonged ( P<0. 05) , no significant change was found in the duration of post-anesthesia care unit stay or incidence of postoperative nausea and vomiting in intranasal dexmedetomidine group ( P>0. 05) . The emergence time was prolonged in intranasal 0. 3-1. 0 μg∕kg dexmedetomidine group ( P<0. 05 ) , and no significant change was found in emergence time in intranasal dexmedetomidine 1. 0-2. 0μg∕kg group ( P>0. 05) . Conclusion Intranasal dexmedeto-midine can decrease the occurrence of agitation during emergence from general anesthesia with sevoflurane and raise the quality of emergence in pediatric patients.

Objective To investigate the electrophysiological protective effect of HTK solution containing sevoflurane on rat cardiac transplantation. Methods Twenty-four male Sprague-Dawley rats were divided into the control group,sevoflurane group and Heptanol group. Rat hearts in 3 groups were stored in HTK solution,containing sevoflurane and sevoflurane+heptanol HTK solution for 6 h. Heart resuscitation time,the duration of arrhythmia and monophasic action potential(MAP)and heart rate(HR)at different time points were recorded.Monophasic action potential duration of repolarization at 50% and 90%(MAPD50 and MAPD90),monophasic action potential amplitude(MAPA)and maximal velocity(Vmax)were analyzed. Results The isolated rat hearts in each group can be successfully restored to the spontaneous heart beat. Compared with group C ,heart resuscitation time in group S and group H was significantly shortened,heart rate(HR)was significantly decreased at T1,MAPD50 and MAPD90 in heart intima and epicardium were shortened at T1 ~ T2,the incidence of ventricular fibrillation and reperfusion arrhythmia Scores were reduced,with the shorter duration of ventricular fibrillation(P<0.05). No significant difference was found in Vmax and MAPA among the three groups at each time point. Conclusion HTK solution containing sevoflurane and HTK solution containing heptanol had similar electrophysiological effects ,which could inhibit the prolonged monophasic action potential(MAP)and reduce arrhythmia. The electrophysiological protective effect of HTK solution containing sevoflurane may be associated with the inhibition of gap junction function.

Objective To evaluate the effect of sevoflurane on memory retrieval in mice and the role of hippocampal PSD95 and amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor.Methods Sixty-four healthy pathogen-free Kuming mice of both sexes,aged 2-3 months,weighing 30-35 g,were divided into control group (n =32) and sevoflurane group (n =32) in a stratified randomized block design.The ability of memory retrieval was evaluated using dark avoidance test.After setting up the memory of dark avoidance,the mice inhaled 40％ oxygen for 2 h in control group and 3.3％ sevofluane in 40％ oxygen for 2 h in sevoflurane group.Dark avoidance test was performed at 12,24,48 and 72 h after the end of oxygen or sevoflurane inhalation (T1-4),and the test results and development of amnesia were recorded.The animals were sacrificed after behavior test at each time point,and brains were removed and cut into sections which were stained with haematoxylin and eosin for examination of the pathological changes of hippocampal CA1 area (under a light microscope) and for determination of the expression of PSD95 and AMPA receptors in hippocampi (using immunohistochemistry and Western blot).Results Compared with control group,the step-in latency and test results of error times were significantly decreased,the expression of PSD95 and AMPA receptors in hippocampus was down-regulated,and the incidence of amnesia was increased at T1 and T2 in sevoflurane group (P＜0.05).Compared with the basic results,no significant change was found in the step-in latency or test results of error times in control group (P＞0.05),and the step-in latency and test results of error times were significantly decreased at T1 and T2 in sevoflurane group (P＜0.05).Apoptosis in pyramidal cells was not found in sevoflurane group.Conclusion Sevoflurane can inhibit the ability of memory retrieval transiently in mice,and the mechanism is related to inhibiting the expression of hippocampal PSD95 and AMPA receptors.

Objective To evaluate the effect of sevoflurane-containing HTK solution on electro-physiological stability of rat donor heart during reperfusion. Methods Male Sprague-Dawley rats, weighing 280-320 g, aged 3 months, in which a Langendorff-perfused isolated rat donor heart model was estab-lished, were used in this study. Sixteen donor hearts were obtained and divided into 2 groups (n＝8 each) using a random number table method: control group (group C) and sevoflurane group (group S). HTK so-lution was used as preservation solution in group C. HTK solution containing 2. 5% sevoflurane was used as preservation solution in group S. Hearts were stored for 6 h in the corresponding preservation solution at 4℃ and then reperfused, and the perfusion temperature was gradually restored to 37 ℃ in two groups. The time of spontaneous recovery of heart beat and development of arrhythmia were recorded. Heart rate, monophasic action potential (MAP) duration at 50% and 90% repolarization (MAPD50, MAPD90), MAP amplitude and maximum velocity and development of early after-depolarization and delayed after-depolariza-tion were recorded at 30 and 45 min of reperfusion. Results Compared with group C, the time of sponta-neous recovery of heart beat was significantly shortened, the incidence of ventricular fibrillation and arrhyth- mia score were decreased, the ventricular fibrillation interval was shortened, and MAPD50and MAPD90of epicardium and endocardium were shortened at 30 and 45 min of reperfusion (P＜0. 05), and no significant change was found in hear rate, maximum velocity or MAP amplitude in group S (P＞0. 05). Early after-de-polarization and delayed after-depolarization were not found in two groups. Conclusion Sevoflurane-contai-ning HTK solution can maintain electrophysiological stability of rat donor heart during reperfusion and de-crease the occurrence of arrhythmia.

Objective To evaluate efficacy of rotigaptide ZP123 on prevention of negative chronotropic effect caused by dexmedetomidine lengthening repolarization duration of the isolated rat hearts.Methods Eighteen healthy adult SD rats of either gender,weighing (300±30) g,were prepared isolated heart perfusion model by Langendorff.After 15 min perfusion and balance of K-H fluid,the isolated hearts were randomly divided into 3 groups (n=6 each): The hearts were continuously pefused for 30 min with 37℃ K-H solution in control group (group C),with dexmedetomidine 50 ng/ml in dexmedetomidine group (group D),or with rotigaptide 80 nmol/L combined with dexmedetomidine 50 ng/ml in rotigaptide combined with dexmedetomidine group (group ZD).In the whole Langendorff-perfused hearts,at the end of balanced infusion for 15 min (T0) and at 15(T1),30(T2) min of continued perfusion with K-H solution,the monophasic action potential (MAP) and heart rate (HR) were recorded from left anterior free wall,MAP duration at 50% repolarization (MAPD50) and at 90% repolarization (MAPD90),monophasic action potential amplitude (MAPA) and maximal velocity (Vmax) were calculated.Results Compared with T0,HR in group D was significantly declined at T1,T2;MAPD90 and MAPD50 in group D were significantly increased at T1,T2 (P<0.05).Compared with groups C and ZD,HR in group D was significantly declined at T1,T2;MAPD90 and MAPD50 in group D were significantly increased at T1,T2 (P<0.05).There was no significant difference in MAPA and Vmax between the three groups.Conclusion Rotigaptide antagonizes negative chronotropic effect induced by dexmedetomidine through shortening monophasic action potential duration in the myocardium of left ventricle of the isolated rat hearts.