ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.

Hepatic ischemia-reperfusion injury （HIRI） is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy， and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies， in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasomes in curcumin-induced reduction of sevoflurane-induced postoperative cognitive dysfunction in rats.Methods:Forty SPF healthy male Sprague-Dawley rats, aged 17-18 months, with body mass index of 580-600 g, were divided into 4 groups ( n=10 each) by a random number table method: control group (C group), postoperative cognitive dysfunction group (P group), curcumin group (CU group), and curcumin+ NLRP3 inflammasome activator group (CN group). The rat model of postoperative cognitive dysfunction was prepared by inhaling 1.5% sevoflurane to explore the abdominal cavity. Curcumin suspension 300 mg/kg was given by intragastric administration in CU group and CN group, and the rats received intragastric administration of nidrisin sodium 5 mg/kg simultaneously in CN group, once a day for 6 consecutive days. Rats received the equal volume of normal saline instead in C group and P group. The frequency of crossing the original platform and time spent in the target quadrant were measured by the Morris water maze test. The histopathological changes of hippocampus were observed by HE staining, neuronal apoptosis was detected by TUNEL staining, and the expression of NLRP3, Bcl-2 and Bax was detected by Western blot. Results:Compared with C group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in P group ( P<0.05). Compared with P group, the frequency of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the apoptosis rate of neurons was decreased, and the expression of NLRP3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in CU group ( P<0.05). Compared with CU group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in CN group ( P<0.05). Conclusions:The NLRP3 inflammasome is involved in curcumin-induced reduction of postoperative cognitive dysfunction in sevoflurane-anesthetized rats.

Objective:To explore the value of ultrasonic velocity vector imaging(VVI)in assessing motion abnormality of myocardial segment of hyperthyroid heart disease.Methods:A total of 76 patients with hyperthyroid heart disease who admitted to hospital from August 2019 to August 2021 were selected.According to the damage degree of ascending aorta of patients,30 patients whose inner diameter of ascending aorta was greater than 30 mm were included in the"inner diameter>30mm"group,and 46 patients whose inner diameter of ascending aorta was less than 30 mm were included in the"inner diameter<30mm"group.Additionally,40 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.All subjects underwent routine echocardiography examination,and the images were imported into the velocity vector imaging(VVI)workstation.And then,the clear and standard two-dimensional grayscale dynamic images were selected to conduct analysis.The left ventricle was tracked and analyzed,and the left ventricular long axis,the apical four chamber,and the velocity of reaching peak value,the time of 50%velocity and the time of 75%velocity of longitudinal myocardial movement of 18 segments of two chambers,as well as the mitral valve level of short axis,the velocity of reaching peak value of reaching peak value,the time of 50%velocity and the time of 75%velocity of radial myocardial movement of 12 segments of horizontal section of papillary muscle,of three cardiac cycles were stored and recorded.Results:There were significant differences in the time to peak of longitudinal contraction at the basal segment and middle segment of left ventricular lateral wall,and the basal segment of front wall,the basal segment,middle segment and apical segment of inferior wall,as well as the basal segment,middle segment and apical segment of posterior wall among three groups(F=45.02,23.19,8.70,19.82,16.17,18.07,36.85,48.65,36.64,P<0.05),respectively.There were significant differences in the velocity and time of reaching peak value of the radial contraction of the levels of papillary muscle and mitral valve of short axis of left ventricular inferior wall among the three groups(F=15.44,40.35,P<0.001),respectively.Conclusion:VVI technique can accurately detect the subtle changes of the synchronization of myocardial systolic motion of left ventricular short axis and long axis of patients with hyperthyroid heart disease,which has higher application value in assessing the abnormalities of myocardial segmental motion of patients with hyperthyroid heart disease.

Objective:Based on the construction of intelligent intensive care unit(ICU)in hospital,to analyze the effectiveness of intelligent ICU life support equipment in clinical decision-making assistance.Methods:The functional modules of the ICU ward interaction system,equipment management system,risk response system and intelligent ward round system were designed to collect information and data of life support equipment in diagnosis and treatment,nursing,operation and technical support in real time to provide medical auxiliary decision-making basis for the improvement of diagnosis,treatment and nursing measures for critically ill patients.115 life-support equipment in clinical use in 3 hospitals including Zhujiajiao People's Hospital of Qingpu District,Shanghai from July 1,2018 to December 31,2022 were selected,the traditional assisted decision-making management mode(referred to as traditional mode,83 sets)and intelligent assisted decision-making management mode(referred to as intelligent mode,89 sets,including 57 units of the traditional mode and 32 newly added units)were adopted respectively.The management level and management effect of life support equipment of the two management modes were compared.Results:The data collection time of the equipment of intelligent mode was(5.67±2.80)min,which was less than that of the traditional mode,the accuracy and completeness of data acquisition,as well as the effective resolution rate of equipment deployment and use,monitoring and alarm,equipment failure and emergency response were(99.02±1.14)%,(94.35±3.46)%,(98.78±0.90)%,(98.99±0.91)%,(88.26±5.31)% and(90.23±5.54)%,respectively,which were higher than those of the traditional mode,the difference between was statistically significant(t=6.504,6.474,3.574,7.620,6.784,4.522,3.719,P<0.05).The effective utilization rates of diagnostic decisions for treatment,care and rehabilitation of intelligent mode equipment were(93.83±3.12)%,(94.99±2.47)% and(91.44±4.62)%,respectively,the comprehensive scores of respiratory function support equipment,circulatory function support equipment,blood purification support equipment and emergency monitoring support equipment were(92.97±4.35)points,(94.34±2.95)points,(93.01±2.44)points and(94.11±1.89)points,respectively,which were higher than those of the traditional mode,the difference was statistically significant(t=4.169,4.875,5.159,4.069,3.033,2.757,6.893,P<0.05).Conclusion:Based on the construction of intelligent ICU,it can improve the quality of life support equipment operation data collection,solve the equipment operation problems in a timely manner,provide an effective basis for the decision-making of diagnosis and treatment,nursing and rehabilitation of critically ill patients,and improve the clinical service level of equipment.