ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

There seems to be a contradiction among the symptoms of"non-thirst"and"thirst after oral use of the decoction"stated in original text 41 of Shang Han Lun(Treatise on Febrile Diseases)and the symptom of"probable thirst"stated in original text 40.In this article,the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction were expounded through the analysis of the basic theories of traditional Chinese medicine about body fluid metabolism and the pathogenic mechanism of thirst,and by synthesizing the relevant articles recorded in Jin Gui Yao Lve(Synopsis of the Golden Chamber)and the understanding of the syndrome of Xiao Qinglong Decoction by later generations of practitioners.After that,the following views are put forward:non-thirst symptom is the primary sympton of the syndrome of Xiao Qinglong Decoction,which results from the disease;thirst after oral use of the decoction is due to drug-induced thirst,which can be classified into the category of physiological thirst;probable thirst symptom is related with fluid consumption by febrile disease,indicating that the disease involves yangming.The analysis of the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction is helpful for evaluation of therapeutic efficacy,and can also be used as the indications of modified medications and differential diagnosis of the disease.The exploration will provide references for the clinical use of Xiao Qinglong Decoction and will be beneficial to improving the clinical efficacy of Xiao Qinglong Decoction.

Objective:To investigate the annual growth rate of obesity prevalence of residents aged 18 and above in China and prevention keypoints for target populations from 2013 to 2018.Methods:This was a cross-sectional study. Subjects from China Chronic Disease and Risk Factor Surveillance project in 2013 and 2018 were included. The prevalence of obesity and growth rate in 31 provinces (autonomous regions and municipalities) in China were collected through survey questionnaires and on-site measurements. Other demographic data such as the proportion of obesity control measures, diet, exercise and drug use was also analyzed. Obesity among adults was defined as body mass index≥28.0 kg/m2.Results:A total of 174 736 residents, aged (51.5±14.2) years, which included 74 704 (42.8%) males were recruited in 2013, and 179 125 residents, aged (55.1±13.8) years, which included 79 337 (44.3%) males were included in 2018. The average annual increase rate of adult obesity prevalence in China from 2013 to 2018 was 3.2% (uncertainty interval ( UI) 2.7%-3.6%), and the average increase rate of obesity prevalence among men (5.2% ( UI 4.6%-5.9%)) was higher than that of women (0.9% ( UI 0.5%-1.3%)). For subgroups analysis, the average increase rate of obesity prevalence among residents aged 18 to 29 (7.4% ( UI 6.9%-7.9%)), education level beyond college degree (6.3% ( UI 5.5%-7.1%)), and unmarried population (11.2% ( UI 10.2%-12.1%)) were higher than that of other subgroups between 2013 and 2018. The residents in Hainan province showed the highest average annual growth rate of obesity. With the exception of Shanxi, Hunan, Gansu and Ningxia province, the annual growth rate of obesity prevalence among adults increased in all other provinces (autonomous regions and municipalities) from 2013 to 2018. For the obese population, the proportion of people who took weight control measures increased from 22.6% in 2013 to 32.7% in 2018. Conclusions:The prevalence of obesity growth characteristics in subpopulations and regions in China are obviously different. Accordingly the focus points of obesity prevention and control in different regions should have their own emphasis.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Objective:To investigate the effect of safflower yellow pigment injection combined with alprostadil on patients after coronary artery bypass grafting(CABG).Methods:A total of 92 patients with coronary heart disease who received CABG in Department of Cardiovascular Surgery,Handan Central Hospital between September 2018 and September 2020 were selected.According to order of admission,they were divided into control group(n=46,from September 2018 to Sep-tember 2019,routine therapy+alprostadil after CABG)and study group(n=46,from October 2019 to September 2020,safflower yellow pigment injection based on control group),both groups were treated for 28d.On 3d after drug withdraw-al,therapeutic effect,cardiac function indexes,four myocardial enzyme spectrum and perioperative indexes were compared between two groups.Results:On 3d after drug withdrawal,compared with control group,patients in study group had sig-nificant higher total effective rate(73.9％vs.91.3％),left ventricular ejection fraction(LVEF)[(55.77±4.48)％vs.(62.18±4.21)％](P=0.028,＜0.001),and significant lower left atrial diameter(LAD)[(36.83±3.45)mm vs.(32.09±3.23)mm],left ventricular end-diastolic diameter(LVEDd)[(49.04±4.65)mm vs.(43.83±5.24)mm],levels of creatine kinase(CK)[(125.13±14.21)U/L vs.(62.56±8.42)U/L],lactate dehydrogenase(LDH)[(203.58±31.63)U/L vs.(156.07±22.26)U/L],aspartate aminotransferase(AST)[(44.25±12.98)U/L vs.(35.41±12.37)U/L]and creatine kinase isoenzyme MB(CK-MB)[(28.11±9.84)U/L vs.(17.59±7.41)U/L](P＜0.001 all).Conclusion:The combination of safflower yellow pigment injection and alprostadil can improve the thera-peutic effect and heart function,and reduce myocardial injury in patients after CABG.

Objective To explore the mechanism of'homotherapy for heteropathy'Zhigancao Decoction in the treatment of coronary heart disease arrhythmia and pulmonary fibrosis by network pharmacology and molecular docking technology.Methods All the active components of Zhigancao Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Herbal Compendium(HERB).The SwissTargetPrediction database was used to predict the targets.Cytoscape software was used to construct the drugs-targets network diagram and network topology analysis was performed to obtain the core drug targets.The disease targets of coronary heart disease,arrhythmia and pulmonary fibrosis were obtained in GeneCards and OMIM databases,and the intersection targets of Chinese medicine and disease were obtained by Venny software.The intersection targets were imported into the STRING online database to construct a protein-protein interaction network,and the data were imported into Cytoscape software for visualization and screening of core targets.Gene ontology(GO)function enrichment analysis and kyto encyclo-pedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using the Metascape database.Molecular docking verification and heat map visualization were performed on the core intersection target and the core drug target through the CB-DOCK2 online platform.Results A total of 137 active components of Zhigancao Decoction were screened out,and 848 corresponding drug targets were obtained by removing repeated values.A total of 9 962 targets of coronary heart disease,5 735 targets of arrhythmia and 7 722 targets of pulmonary fibrosis were obtained.A total of 362 drug-disease intersection targets were obtained by Venny platform processing.The potential core targets with higher degree values were GAPDH,IL-6,ALB,STAT3,TNF,MMP-9 and so on by network topology analysis.GO functional enrichment analysis showed that the main biological processes(BP)involved in Zhigancao Decoction'homotherapy for heteropathy'were the response to hormones,the positive regulation of circulatory system process,phosphorus metabolism process,the response to exogenous stimulation,and the response to organic matter,the main cellular components(CC)include lipid rafts,receptor complexes,cytoplasmic perinuclear regions,dendrites,membrane sides,etc.,the main molecular functions(MF)include protein kinase activity,kinase binding,protein homopolymerization activity,nuclear receptor activity,heme binding,etc..KEGG pathway enrichment analysis showed that the main signaling pathways involved in Zhigancao Decoction'homotherapy for heteropathy'were lipid and atherosclerosis,calcium signaling pathway,cAMP signaling pathway,insulin resistance,cGMP-PKG signaling pathway,JAK-STAT signaling pathway,NF-κB signaling pathway,etc..The results of molecular docking suggested that there was a good binding activity between the main active component targets of Zhigancao Decoction and the core targets of'homotherapy for heteropathy'.Conclusion Zhigancao Decoction mainly regulates JAK-STAT,NF-κB,cAMP and other signaling pathways,acts on IL-6,STAT3,TNF,MMP-9 and other gene targets,and exerts the effect of'homotherapy for heteropathy'on coronary heart disease arrhythmia and pulmonary fibrosis.