ObjectiveBased on ultra performance liquid chromatography-mass spectrometry（UPLC-MS） and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis（CAG） rats with liver-depression and spleen-deficiency， and to look for the correlation between cerebral cortex， hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction， hunger and satiety disorders， chronic restraint and tail clamping stimulation， lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling， 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg^-1 by gavage， and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics， behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex， hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group， the macroscopic characteristics of rats in Chaishao Liujuntang group were improved， such as hair color， mental state and stool properties， and the number of times of crossing and standing in the open field experiment was significantly increased， and the static time of forced swimming was significantly reduced（P<0.01）， and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers， but not enriched in pathways， 26 common potential biomarkers were identified in the hypothalamus， and the key metabolic pathways involved were mainly enriched in purine metabolism， glycerol phospholipid metabolism， D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach， and the key metabolic pathways involved were mainly enriched in thiamine metabolism， valine， leucine and isoleucine biosynthesis， and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex， hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex， hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics， mainly manifested by changes in the content of glycerol phospholipids， fatty acids and bile acid metabolites. Moreover， Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.

Objective:To evaluate the effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) by the random number table method: control group (CM group), sevoflurane group (CS group), monocrotaline group (M group) and sevoflurane + monocrotaline group (S group). Monocrotaline 60 mg/kg was intraperitoneally injected in group M and group S, and monocrotaline lysate was intraperitoneally injected in group CM. The rats in S and CS groups inhaled 2.5% sevoflurane for 1 h, twice a week, at an interval of 3 days starting from the first day after injection of monocrotaline. Pulmonary artery acceleration time and pulmonary artery ejection time were measured by transthoracic echocardiography at 6 weeks after monocrotaline injection. The chest was exposed under 3% sevoflurane anesthesia, the heart was perfused, and the pulmonary artery branch and right ventricular myocardial tissues were retained. The wall thickness of pulmonary arterioles and cross-section area of right ventricular cardiomyocytes were observed by HE staining. The expression of Ca 2+ transporter in right ventricular cardiomyocytes was detected by Western blot. Results:Compared with CM group, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly decreased, the cross-section area of right ventricular cardiomyocytes was increased, the wall thickness of pulmonary arteriole was increased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was up-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was down-regulated in M group ( P<0.01). Compared with group M, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly increased, the cross-section area of right ventricular cardiomyocytes was decreased, the wall thickness of pulmonary arteriole was decreased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was down-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was up-regulated in group S ( P<0.01). Conclusions:The mechanism by which sevoflurane improves right ventricular remodeling is related to regulating the expression of Ca 2+ transporter in cardiomyocytes of rats with pulmonary arterial hypertension.

Anxiety and depression are prevalent conditions in the geriatric department, leading to significant patient suffering and imposing substantial economic and social burdens.The incidence of anxiety and depression has been on the rise.Currently, the primary treatment approaches encompass drug therapy, physical therapy, and psychological intervention.However, due to the fact that most elderly individuals are unable to tolerate the side effects of medications and have low acceptance of psychological interventions, these treatment options alone are not sufficient for addressing anxiety and depression in this population.As a result, exercise therapy has emerged as a recommended treatment method in both domestic and international guidelines.This approach offers several advantages, including fewer side effects, cost-effectiveness, and controllable implementation.Nevertheless, it is crucial to develop an appropriate exercise prescription that encompasses the specific type, intensity, frequency, and duration of exercises.This paper aims to discuss the effect of exercise therapy, including exercise type, intensity, and frequency, as well as the mechanism of exercise intervention.

Objective:To explore the effects of intrahippocampal injection of ferroptosis inducer Erastin on depressive- and anxiety-like behavior and the expression of ferroptosis-related proteins in rats.Methods:Forty 6-week-old healthy male Sprague-Dawley rats were randomly divided into five groups ( n=8/group): Control group, Erastin low-dose(200 ng/μL) group, Erastin medium-dose(400 ng/μL) group, Erastin high-dose group(600 ng/μL) and lipopolysaccharide (LPS, 10 μg/L) group.After the intrahippocampal injection of Erastin(2.5 μL per side), body weight, and behavioral tests, including sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and elevated plus maze (EPM), were performed to evaluate depressive- and anxiety-like phenotypes from the fourth day after injection.The levels of ferroptosis-related proteins and mRNA, including glutathione peroxidase 4 (GPX4), cyclo-oxygenase 2 (COX2), ferritin heavy polypeptide 1 (FTH1), long-chain fatty acyl-CoA synthetase 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) were measured using real-time quantitative PCR and Western blot analysis.SPSS 22.0 software was used for statistical analysis.One-Way ANOVA was used for multi-group comparison, and LSD was used for further pound-wise comparison. Results:(1)Body weight and behavioral tests: there were no statistically significant differences in baseline body weight and behavioral tests in these groups ( F=0.02-1.15, all P>0.05). After intrahippocampal injection, compared with the control group, medium-dose Erastin induced depression-like behaviors in rats more significantly, as indicated by reduced bodyweight ((245.20±5.24)g, (267.45±13.16)), sucrose preference in SPT ((32.14±8.51)%, (68.17±13.67)%), central time in OFT ((6.01±2.57)s, (16.49±7.21)s), percentage of time in open arm in EPM ((5.00±3.83)%, (19.63±5.91)%) and increased immobility time in FST ((37.00±7.58)s, (12.50±5.51)s) and percentage of time in closed arm in EPM ((89.43±4.77)%, (59.96±9.91)%), and there were statistically significant differences in these groups (all P<0.05). (2)The expression of ferroptosis-related indicators: after intrahippocampal injection, the expression of mRNA ( F=2.23, 8.37, 2.91, 7.60, 3.16, all P<0.05) and protein ( F=3.31, 40.13, 8.52, 3.70, 70.79, all P<0.05) of FTH1, GPX4, SLC7A11, COX2 and ACSL4 in hippocampus were statistically significant differences in the 5 groups.The mRNA and protein levels of FTH1, GPX4 and SLC7A11 in Erastin medium-dose group were lower than those in the control group (all P<0.05), while the mRNA and protein levels of COX2 and ACSL4 were higher than those in the control group (all P<0.05). Conclusion:Intrahippocampal microinjection of Erastin(400 ng/μL) can induce ferroptosis in hippocampus of rats and can also induce depressive-like behaviors in rats.

Depression is a common psychiatric disorder characterized by low mood with complex pathophysiological mechanisms and poor effect of pharmacological treatment.The animals were placed in greater sensory, physical and/or social stimuli than those of the standard feeding environment, so that they can obtain positive plasticity and adaptability.Environmental enrichment(EE) is a common intervention to improve brain function in laboratory.A large number of studies have shown that EE had significant ameliorative effects on various animal models of depression, but the mechanisms have not been yet fully understood with outcome heterogeneity in ethology.There was no universally accepted and unified paradigm and standard for EE due to its multi-dimensionality and complexity.Therefore, it is necessary to improve the structural components and implementation steps of EE by integrating the existing data.Combined with recent studies on animal models of depression, this paper reviewed the anti-depression mechanism of EE from promoting hippocampal neurogenesis, reducing neuroinflammation, regulating neuroendocrine and affecting epigenetic modifications, in order to provide new ideas for mechanisms research and treatment of depression.As the rise of precision medicine and individualized medicine brings human growing interest in exploring the sources and mechanisms of inter-individual differences and intra-group effects of depression, it will be a challenge to translate EE to the human society in a rational way.

Objective    To evaluate whether long frozen elephant trunk (FET) increases the risk of spinal cord injury in patients with acute type A aortic dissection. Methods    From 2018 to 2019, 172 patients with acute type A aortic dissection were treated in Guangdong Provincial People’s Hospital. They were divided into two groups according to the length of FET: patients treated with stents of 100 mm in length were enrolled into a short FET group, and those with stents of 150 mm in length into a long FET group. There were 124 patients in the short FET group, including 108 (87.1%) males and 16 (12.9%) females with a mean age of 51.8±7.9 years. There were 48 patients in the long FET group, including 44 (91.7%) males and 4 (8.3%) females with a mean age of 50.6±9.7 years. The clinical data and prognosis of the patients were analyzed. Results    The mean distal stent graft was at the level of T 8.5±0.7 in the long FET group, and at the level of T 6.8±0.6 in the short FET group (P=0.001). Sixteen patients died after operation in the two groups, including 13 (10.5%) in the short FET group and 3 (6.2%) in the long FET group (P=0.561). There were 7 patients of spinal cord injury in the two groups, including 6 (4.8%) in the short FET group and 1 (2.2%) in the long FET group (P=0.675). There was no statistical difference in other complications between the two groups. The follow-up time was 16.7 (1-30) months. During the follow-up, 2 patients died in the long FET group and 5 died in the short FET group. No new spinal cord injury or distal reintervention occurred during the follow-up. Conclusion    Long FET does not increase the incidence of spinal cord injury in patients with acute type A aortic dissection.

Objective To investigate the value of albumin-bilirubin (ALBI) grade in evaluating liver function changes and prognosis of hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). Methods PubMed, the Cochrane Library, EMbase, Web of Science, OVID, CNKI, Wanfang Data, VIP, and CBM databases were searched for studies on ALBI grade for evaluating liver function changes and prognosis of HCC patients undergoing TACE published up to December 2020. After quality assessment and data extraction, RevMan 5.3 was used to perform a meta-analysis of the studies included. The chi-square test was used to evaluate heterogeneity between studies; hazard ratio ( HR )/odds ratio ( OR ) and corresponding 95% confidence interval ( CI ) were used to evaluate outcome measures; funnel plots were used to assess publication bias. Results A total of 18 articles were included, with 9940 patients in total. The meta-analysis showed that the HCC patients with higher ALBI grades after TACE had a shorter overall survival time than those with lower ALBI grades (2 nd vs 1 st : HR =1.48, 95% CI : 1.39-1.57, P < 0.000 01; 3 rd vs 1 st : HR =2.45, 95% CI : 1.92-3.13, P < 0.000 01; 3 rd vs 2 nd : HR =1.91, 95% CI : 1.71-2.13, P < 0.000 01). The degree of deterioration of ALBI caused by 2 times of TACE was higher than that caused by 1 time of TACE ( OR =1.91, 95% CI : 1.27-2.88, P < 0.05); the degree of deterioration of ALBI caused by 3 times of TACE was higher than that caused by 1 time of TACE ( OR =3.21, 95% CI : 1.95-5.28, P < 0.05); the degree of deterioration of ALBI caused by 3 times of TACE was higher than that caused by 2 times of TACE ( OR =1.70, 95% CI : 1.07-2.70, P < 0.05). In addition, ALBI grade could predict the onset of acute-on-chronic liver failure (ACLF) after TACE ( OR =4.57, 95% CI : 2.76-7.57, P < 0.000 01). Conclusion Repeated TACE treatment can cause continuous deterioration of liver function based on ALBI, and ALBI has an important clinical value in predicting prognosis and the risk of ACLF after TACE.

Objective:To evaluate the effects of sevoflurane on right ventricular myocardial fibrosis caused by pulmonary arterial hypertension (PAH) in rats.Methods:Eighteen SPF healthy adult male Wistar rats, weighing 260-300 g, were divided into 3 groups ( n=6 each) by a random number table method: control group (group C), group PAH and PAH plus sevoflurane group (group PS). The PAH model was established by single intraperitoneal injection of monocrotaline 60 mg/kg in group PAH and group PS, while the equal volume of normal saline was intraperitoneally injected in group C. Sevoflurane 1.5 MAC was inhaled for 1 h starting from the end of injection, twice a week for 6 weeks in total, in group PS.Echocardiography was performed at the end of 6th week to measure right ventricular end-diastolic diameter (RVEDD), right ventricular anterior wall end-diastolic thickness (RVWTd), interventricular septal end-diastolic thickness (IVSTd), pulmonary artery inner diameter (PAID) and pulmonary valve orifice maximum peak velocity (PV). At the end of 6th week, the hearts were taken to measure the weight of right ventricle, interventricular septum and left ventricle, and Fulton′s index was calculated, and the tissue of the lower lobe of the right lung was taken, the outer diameter and inner diameter of the vascular wall were measured to calculate the vascular wall thickness index (WT), and total vascular area and lumen area were measured to calculate the vascular wall area index (WA) after HE staining.The myocardial tissue of the right ventricle was obtained to observe the degree of myocardial fibrosis (with a light microscope after Masson staining) and to detect the expression of TGF-β1 (after immunofluorescence staining) and expression of TGF-β1, phosphorylated Smad3 (p-SMad3) and Smad7 (by Western blot). Results:Compared with group C, Fulton′s index, RVEDD, RVWTd, IVSTd, PAID, WT and WA were significantly increased, PV was decreased, the expression of TGF-β1 and pSmad3 in right ventricular myocardial tissues was up-regulated, the expression of Smad7 was down-regulated( P<0.01), and myocardial fibrosis occurred in group PAH.Compared with group PAH, Fulton′s index, RVEDD, RVWTd, IVSTd, PAID, WT and WA were significantly decreased, PV was increased, the expression of TGF-β1 and pSmad3 in right ventricular myocardial tissues was down-regulated, the expression of Smad7 was up-regulated ( P<0.05 or 0.01), and myocardial fibrosis was significantly improved in group PS. Conclusion:Sevoflurane can improve the myocardial fibrosis in right ventricle induced by PAH in rats, and the mechanism may be related to inhibiting activation of TGF-β1/Smad3 signaling pathway.

A series of triazole derivatives were designed and synthesized based on a natural product cembrane separated from Croton laevigatus Vahl which showed potential antitumor activity against HeLa cells.Twelve novel compounds were synthesized and their structures were characterized by 1H NMR, 13C NMR and HRMS.Their cytotoxicities in vitro were evaluated for HeLa,K562 and K562/A02 cells by MTT assay.The results showed that some cembrane derivatives possessed antitumor activities.Substituted triazole connected to cembrane derivatives exhibited potent activity toward drug-resistant K562/A02 cells.

Objective To evaluate the role of the angiotensin Ⅱ type 2 receptor (AT2R) in repeated propofol anesthesia-induced neuroapoptosis in the basal ganglia of newborn rats.Methods Fiftyfour pathogen-free Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),repeated propofol anesthesia group (group P) and AT2R agonist CGP42112A group (group G).In group C,0.9％ sodium chloride injection 3 ml/kg was intraperitoneally injected,and half of the initial dose 1.5 ml/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group P,propofol 30 mg/kg was intraperitoneally injected,and half of the initial dose 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group G,CGP42112A 1 mg/kg was intraperitoneally injected,propofol 30 mg/kg was intraperitoneally injected 5 min later,and half of the initial dose of propofol 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.Six rats were sacrificed at 2 h after emergence from anesthesia,and brains were removed for detection of neuroapoptosis in the basal ganglia by TUNEL assay.The apoptosis index was calculated.Another 6 rats were sacrificed,and the basal ganglia were isolated from brains to detect the expression of activated caspase-3,AT2R and peroxisome proliferator-activated receptor gamma (PPARγ) (by Western blot) and the expression of AT2R and PPARγ mRNA (by real-time polymerase chain reaction).The other 6 rats were fed until 28 days old,and the cognitive function was then assessed using Morris water maze test.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the target quadrant was shortened,the frequency of crossing the platform was decreased,the apoptosis index of the basal ganglia was increased,the expression of activated caspase-3 was up-regulated,and the expression of AT2R and PPARγprotein and mRNA was down-regulated in group P (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group P,the escape latency was significantly shortened,the time of staying at the target quadrant was prolonged,the frequency of crossing the platform was increased,the apoptosis index of the basal ganglia was decreased,the expression of activated caspase-3 was down-regulated,and the expression of AT2R and PPARγ protein and mRNA was up-regulated in group G (P＜0.05).Conclusion Inhibited activation of AT2R is involved in repeated propofol anesthesia-induced neuroapoptosis in the basal ganglia of newborn rats.