OBJECTIVE To study the efficacy evaluation of triptolide(TP) in rats with cerebral ischemia-reperfusion(I/R) injury and its mechanism. METHODS Rat brain I/R injury model was copied by middle cerebral artery wire embolism surgery, and TP (0.1, 0.2 mg·kg−1) was given to the treatment group, and set the sham surgery group. The Longa score method was used to measure the neural function of rats, and Niselferi staining was used to show the morphology of neurons in the ischemic side brain tissue of rats, immunofluorescence was used to detect the expression levels of MAP2 and Syn in ischemic lateral brain tissue. The expression levels of cAMP, PKA, BDNF, Syn and PSD-95 were detected by Western blotting. RESULTS Compared with the model group, the neurological scores of TP treatment group decreased significantly(P<0.01 or P<0.001), it had a protective effect on damaged neurons. Compared with the model group, cAMP, PKA, BDNF, Syn and PSD-95 in TP treatment group were significantly up-regulated. CONCLUSION TP treatment can significantly improve I/R injury, and the mechanism may be related to the activation of the cAMP/PKA/BDNF signaling pathway.

OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

Objective:To investigate the effect of Hong's One Stitch Method in pancreaticoduodenectomy(PD).Methods:A total of 40 patients who underwent PD in our hospital from Jan 2021 to Dec 2022 were divided into two groups according to random number table method,with 20 patients in each group.The control group was treated with end to end pancreatojejunal anastomosis,and the observation group was treated with"Hong's One Stitch Method".The perioperative indicators,complications,secondary surgery,mortality and quality of life were compared between the two groups.Results:The pancreatoenteroanastomosis time,operation time and hospitalization time in the observation group were shorter than those in the control group,and the incidence of pancreatic fistula was lower than that in the control group(P＜0.05).There were no significant differences in intraoperative blood loss,pancreatic biochemical leakage,bile fistula,hemorrhage,localized abdominal infection,gastric emptying obstruction,pulmonary infection,secondary surgery and mortality between the two groups(P＞0.05).The mental health score,emotional function score,social function score,energy score,general health status score,body pain score,and physiological function score in the observation group were higher than those in the control group(P＜0.05).Conclusion:In PD surgery,the application of"Hong's One Stitch Method"to perform pancreatoenterostomy is beneficial to shorten the pancreatoenterostomy time,operation time and hospitalization time,accelerate the postoperative recovery,reduce the incidence of pancreatic fistula,and improve the quality of life of patients.

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

The pathophysiological mechanisms of subarachnoid hemorrhage (SAH) include early brain injury (EBI) and delayed cerebral ischemia. In recent years, researches have mainly focused on EBI. After blood enters the subarachnoid space, it can cause neuronal apoptosis, blood-brain barrier disruption, brain edema and neuroinflammation. Red blood cells and their metabolites activate resident immune cells in central nervous system and recruit peripheral inflammatory cells tinto the subarachnoid space, inducing neuroinflammation. The latter plays an important role in EBI and has a significant impact on the outcome of patients with SAH. This article reviews the role of neuroinflammation in EBI after SAH.

A three-dimensional feature construction method based on spectral information is presented,in which the power values of each channel are arranged into two-dimensional feature vectors based on electrode positions.The different frequency band features are arranged into a three-dimensional integral feature tensor to extract the information in frequency domain.Meanwhile,in order to reduce the influence of volume conductor effect,functional connectivity is utilized to map the temporal electroencephalogram data to the spatial brain functional network for extracting the spatial information.By analyzing the relationship between features and target classes,a 3D-CNN-Attention network model is proposed to incorporate an Attention mechanism in 3D-CNN network to enhance the electroencephalogram feature learning capability.A series of comparative experiments on publicly available datasets show that 3D-CNN-Attention network framework outperforms other methods in depression detection,obtaining an accuracy rate of up to 96.32%.The proposed method provides an effective solution for depression detection.

Objective To investigate the effect of Gegen Qinlian Decoction on liver energy metabolism and free fatty acid(FFA)in rats with insulin resistance(IR).Methods IR rat model was established by feeding 60%fat high-fat diet for 13 consecutive weeks.SD rats were randomly divided into normal group,model group,Rosiglitazone(5 mg·kg-1)group and Gegen Qinlian Decoction low-,medium-and high-dose groups(1.65,4.96,14.86 g·kg-1),with 6 rats in each group.Intragastric administration was given once a day,continuous administration intervention lasted for 16 weeks.Determination of IR-related indicators:serum fasting insulin(FINS),fasting blood glucose(FPG),calculate the IR index;HPLC method was established for the determination of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)in rat liver tissue;ELISA was used to determine the content of FFA in rat liver tissue.The contents of serum total cholesterol(TC)and triglyceride(TG)were detected by automatic biochemical analyzer.The pathological changes of liver tissue were observed by HE staining.Results(1)After the model replication,compared with the normal group,the FINS,FPG levels and IR index of the model group were significantly increased(P＜0.05).(2)Compared with the normal group,the levels of FINS,FPG and IR index in the model group were significantly increased(P＜0.01),the contents of ATP,ADP and AMP in liver tissue were significantly decreased(P＜0.01),the content of FFA was significantly increased(P＜0.01),and the levels of TC and TG in serum were significantly increased(P＜0.05).Liver cells arranged in disorder,fatty degeneration,and there are a large number of lipid droplets.Compared with the model group,the FINS level and IR index of rats in each administration group were significantly decreased(P＜0.05,P＜0.01),and the FPG level of rats in the Rosiglitazone group was significantly decreased(P＜0.05).The contents of ADP and AMP in liver tissue of rats in each administration group were significantly increased(P＜0.05,P＜0.01),and the contents of ATP in liver tissue of rats in low-,medium-and high dose-groups of Gegen Qinlian Decoction were significantly increased(P＜0.05,P＜0.01).The content of FFA in liver tissue of rats in Rosiglitazone group and Gegen Qinlian Decoction low-and high-dose groups was significantly decreased(P＜0.01).The serum TC level of rats in the low-and high-dose groups of Gegen Qinlian Decoction was significantly decreased(P＜0.05,P＜0.01),and the serum TG level of rats in the Rosiglitazone group and the low-dose group of Gegen Qinlian Decoction was significantly decreased(P＜0.05,P＜0.01).The steatosis of hepatocytes in rats of each administration group was alleviated to varying degrees,and the lipid droplets were reduced,and the pathological damage was improved.Conclusion Gegen Qinlian Decoction may improve liver lipid metabolism disorder and restore lipid and energy balance by regulating energy metabolism and reducing FFA level,thus improving IR.

The causes of mental disorders are complex, and early recognition and early intervention are recognized as effective way to avoid irreversible brain damage over time. The existing computer-aided recognition methods mostly focus on multimodal data fusion, ignoring the asynchronous acquisition problem of multimodal data. For this reason, this paper proposes a framework of mental disorder recognition based on visibility graph (VG) to solve the problem of asynchronous data acquisition. First, time series electroencephalograms (EEG) data are mapped to spatial visibility graph. Then, an improved auto regressive model is used to accurately calculate the temporal EEG data features, and reasonably select the spatial metric features by analyzing the spatiotemporal mapping relationship. Finally, on the basis of spatiotemporal information complementarity, different contribution coefficients are assigned to each spatiotemporal feature and to explore the maximum potential of feature so as to make decisions. The results of controlled experiments show that the method in this paper can effectively improve the recognition accuracy of mental disorders. Taking Alzheimer's disease and depression as examples, the highest recognition rates are 93.73% and 90.35%, respectively. In summary, the results of this paper provide an effective computer-aided tool for rapid clinical diagnosis of mental disorders.
Humans ; Mental Disorders/diagnosis* ; Alzheimer Disease/diagnosis* ; Brain Injuries ; Electroencephalography ; Recognition, Psychology

Objective:To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa, and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients.Methods:DNA was extracted from peripheral blood samples of members from two families with dystrophic epidermolysis bullosa, and subjected to high-throughput sequencing and Sanger sequencing.Results:The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa, and the symptoms of the proband in family 1 were more serious than those of other patients in the family. Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C (p.G2028R) in the COL7A1 gene, and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2 (IVS91) T>G in the COL7A1 gene, both of which were first reported. The proband in family 2 carried the mutations c.6081_6082 ins C (p.G2028Rfs*71) and c.1892G>A (p.W631X, first reported) in the COL7A1 gene, which were inherited from her father and mother, respectively.Conclusion:The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1; the first reported mutations enriched the mutation spectrum of the COL7A1 gene.

OBJECTIVE To optimize the heart-nourishing granule extraction process by network pharmacology and Box-Behnken response surface method. METHODS The active ingredients of heart-nourishing granule were excavated through network pharmacology and their mechanism of action in the treatment of coronary heart disease was preliminarily explored. Molecular docking technology was used to predict the binding ability of the active ingredients to the main targets. At the same time, based on the compatibility relationship between the monarch, minister, assistant and guide of the prescription, the pharmacological effects of the ingredients, and the content determination index components of each medicinal flavor in the 2020 edition of the Chinese Pharmacopoeia, the process evaluation index components of heart-nourishing granule were further determined. In addition, combined with the analytic hierarchy process to determine the weight of each component, the Box-Behnken response surface method was used to optimize the extraction process of heart-nourishing granule. RESULTS The main active components of heart-nourishing granule screened were catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin. By acting on core targets such as AKT1, IL-6, IL-1b, VEGFA, JUN and MAPK3, they regulated lipid and atherosclerosis, MAPK signaling and other pathways played a role in the treatment of coronary heart disease. Molecular docking results showed that the binding energies of active components and core targets predicted by network pharmacology were all < -5.0 kJ·mol-1. Five components catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin were calculated by analytic hierarchy process method. The weight coefficients of arginyl glycosides were 0.329 7, 0.329 7, 0.164 8, 0.109 9, and 0.065 9, respectively. The Box-Behnken response surface method obtained the optimal water extraction process: 10 times the amount of water was used to extract twice, and each time was decocted for 1.5 h. The verification test showed that the contents of the five components were consistent with the predicted values, and the RSD values were all <5%. CONCLUSION The extraction process of heart-nourishing granule based on network pharmacology and Box-Behnken response surface methodology is stable and feasible, which provided an experimental basis for its further quality improvement.