OBJECTIVE To investigate the effects and mechanism of total alkaloids of Corydalis Rhizoma （TAC） on the regulation of cuproptosis in rats with diabetic cardiomyopathy （DCM） based on silence information regulator 1（Sirt1）/tumor protein 53（P53）signaling pathway. METHODS DCM rat model was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. Thirty-two model rats were randomly divided into model group， TAC low-dose， medium-dose and high-dose groups （7， 10.5， 14 mg/kg）， with 8 rats in each group. An additional 8 rats were assigned to normal control group. Related drugs or normal saline were administered intragastrically in each group， once a day， for 4 weeks. After the last medication， the fasting blood glucose （FBG） levels of the rats were measured. The levels of myocardial creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in serum and myocardial tissue of rats were all detected. The pathological morphology， fibrosis degree， and Cu2+ deposition of myocardial tissue in rats were observed. The levels of Cu2+ and glutathione （GSH） in myocardial tissue， the expressions of Sirt1/P53 signaling pathway-related proteins [Sirt1， P53， solute carrier family 7 membrane 11 （SLC7A11）]， and iron-sulfur cluster-related proteins [ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， aconitase 2 （ACO2）， NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）， dihydrolipoamide acetyltransferase （DLAT）， dihydrolipoamide succinyltransferase （DLST）]， and heat shock protein 70 （HSP70） were all determined. RESULTS Compared with normal control group， the model group exhibited significantly elevated levels of FBG， CK， CK-MB and LDH in both serum and myocardial tissue， as well as increased 2+ levels of Cu in myocardial tissue and the expression of P53 and HSP70 proteins （P＜0.05）； the level of GSH and the expression levels of Sirt1， SLC7A11， FDX1， LIAS， ACO2， NDUFS8， DLAT， and DLST proteins in myocardial tissue were all significantly decreased （P＜0.05）； the myocardial tissue exhibited severe pathological damage， with numerous inflammatory cell infiltrations and significant fibrosis， as well as increased deposition of Cu2+. Compared with model group， most of the above quantitative indicators in rats were significantly reversed in TAC groups （P＜0.05）； the pathological damage to the myocardial tissue was alleviated， with reduced fibrosis and Cu2+ deposition. CONCLUSIONS TAC can ameliorate DCM in rats， and its mechanism of action may be related to activating the activity of the Sirt1/P53 signaling pathway， promoting the chelation of GSH with Cu2+， and inhibiting cuproptosis of cardiomyocyte.

Evoked Potentials ; Social Isolation ; Attention ; Humans

By applying "homeostasis" to the study of the meridian and collateral system， the concept of meridian and collateral homeostasis has been proposed which refers to a balanced and stable state of meridian and collateral system， and plays an important role in maintaining body health and can provide a reference for the diagnosis and treatment of diseases. Phenomics realizes the cross-scale correlation from micro-phenotypic data， such as genome， proteome， and metabolome， to macro-phenotypic data， such as physiological state， behavioral activities， and external manifestations. From the perspective of phenomics， this paper proposes a meridian and collateral homeostasis dynamic mapping model of "macroscopic signs and microscopic expression". This model combines macro signs such as the four examinations of traditional Chinese medicine （TCM）， biophysical indicators of acupoints， and micro expression information such as genes， proteins， and metabolism， and systematically investigates the relationship between meridian and collateral homeostasis and health and disease， thereby providing ideas and references for the identification of pre-disease states as well as precise diagnosis and treatment in TCM.

Objective To construct a morphological brain network in patients with cerebral small vessel disease(CSVD)and predict it application for cognitive function.Methods A total of 64 eld-erly CSVD patients admitted in our hospital from January 2020 to February 2024 were retrospec-tively recruited.Cognitive function was assessed with Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Their clinical data,and results of cognitive function and multi-modal MRI scanning were collected and analyzed.3D T1-weighted imaging based on Kullback-Leibler divergence similarity was used to construct individual morphological brain net-work,and the connectome-based predictive model was employed to construct a cognitive predic-tion model.Results The network,which is significantly and positively correlated with the MMSE and MoCA scores,was mainly located in the default mode network,and could effectively predict individual MMSE and MoCA scores(r=0.795,P=4.436×10-15;r=0.794,P=4.974×10-15,P＜0.01).The connections,which were significantly negatively correlated with MMSE or MoCA scores,were mainly located between the salience/ventral attention network and other networks,and could also effectively predict individual MMSE and MoCA scores(r=0.766,P=1.679× 10-13;r=0.850,P=6.915×10-19,P＜0.01).Combined positive correlation and negative correla-tion networks,the model showed further improved predictive performance(r=0.849,P=7.603 × 10-19;r=0.888,P=1.445 × 10-22,P＜0.01).Conclusion Individual morphological brain network can effectively predict cognitive function in elderly CSVD patients,and can be used as a convenient tool for early warning of cognitive impairment related to CSVD.

ObjectiveA method was developed for the rapid determination of 18 common disinfection by-products including halogenated oxides and haloacetic acid （HAAs） in drinking water by high performance liquid chromatography tandem mass spectrometry （HPLC-MS/MS）. MethodThe water sample was filtered by 0.22 μm hydrophilic membrane then the analytes were separated on a PFP （2.1 mm× 100 mm， 2.7 μm） pentafluorophenyl column with 0.1% acetic acid and acetonitrile as mobile phase gradient elution. Ionization in anionic electrospray mode was detected by multi-reaction monitoring （MRM） mode. The external standard method was used for quantitation. ResultsThe correlation coefficients of 18 disinfection by-products were above 0.999 in the corresponding linear range. The average spiked recoveries of 1， 10 and20 times of LOQ of each analyte were 91.6%‒101.8%， and the relative standard deviation （RSD） was 1.2%‒6.4%. The LOD and LOQ were 0.020‒2 μg·L^-1 and 0.050‒5 μg·L^-1， respectively. ConclusionThis method is simple， sensitive and accurate， and could be used for the routine analysis of 18 common disinfection by-products in drinking water.

The main clinical manifestation of dyslipidemia is hyperlipidemia， which is an important risk factor leading to the occurrence of cardiovascular and cerebrovascular diseases such as atherosclerosis， coronary heart disease and stroke. In clinical practice， lipid-lowering drugs are mainly used for treatment， but there are issues such as individual differences and genetic effects. Therefore， it is necessary to perform gene detection on patients， so as to guide individualized application of lipid-lowering drugs. This review mainly previews the definition of gene detection and the individualized treatment of lipid-lowering drugs， and introduces the application of gene detection in the individualized treatment of lipid-lowering drugs （statins， fibrates， nicotinic acid and ezetimibe）. Among them， the gene polymorphisms of APOE， SLCO1B1 and CYP450 family play a key role in the efficacy and safety of statins； the gene polymorphisms of APOA/B/C family have a significant impact on the efficacy of fenofibrate； the gene polymorphisms of HCAR2 and DGAT2 have an important impact on the efficacy of niacin； the gene polymorphisms of NPC1L1 have a significant impact on the efficacy of ezetimibe. It is suggested to conduct genotype detection for patients with dyslipidemia to select appropriate treatment strategies， so as to provide individualized medication guidance.

Objective To investigate the effect of total alkaloids of Rhizoma Corydalis(TAC)on the expression of silencing information regulator 1(Sirt1)/tumor suppressor P53 protein signaling pathway-related proteins in the hippocampus of rats with chronic cerebral ischemia(CCH),and to explore its mechanism.Methods The rats were randomly divided into Sham operation group,model group,TAC high-dose group(14 mg/kg)and TAC low-dose group(7 mg/kg),with 6 rats in each group.A modified bilateral common carotid artery permanent occlusion method(BCCAO)was used to establish a rat model of CCH,and only bilateral common carotid arteries were separated in the Sham group.After the modeling was completed,each group was given the corresponding drug or isotonic saline by gavage,once a day,and the treatment lasted for 14 days.Hematoxycin-eosin staining was used to observe the pathological changes in the hippocampus of rats,in situ terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphate-biotin nick end labeling assay(TUNEL)was used to detect neuronal apoptosis,and Western blotting and immunohistochemistry were used to detect expression of Sirt1,P53,P53 positive apoptosis regulator(PUMA),B-cell lymphocytoma-2(Bcl-2)protein,Bcl-2-related X protein(BAX),respectively in the hippocampus of rats.Results(1)There were significant differences in the number of apoptotic cells and apoptosis rate among the four groups(F-values were 71.417 and 76.835,respectively,both P＜0.01).There were statistically significant differences in the mean integral optical density values of Sirt1,P53,PUMA,BAX and Bcl-2 protein positive expression areas among the four groups(F-values were 1 178.390,42.465,867.413,110.656 and 131.801,all P＜0.01).There were significant differences in the relative expression levels of Sirt1,P53,PUMA,BAX and Bcl-2 among the four groups(F-values were 9.497,11.863,58.552,186.855 and 12.466,all P＜0.01).(2)Compared with the Sham operation group,the neuronal arrangement of brain tissue in the hippocampus of the model group was disordered,the nuclear consolidation increased,and the glial cells and inflammatory cells increased significantly,and the number and apoptosis rate of neurons in the hippocampus of the model group increased significantly(respectively[10.8±1.5]cells vs.[2.0±0.9]cells and[35.5±4.5]％vs.[6.2±2.6]％;both P＜0.05),and the average integral optical density values of the positive expression areas of Sirt1 and Bcl-2 proteins decreased significantly(84.6±6.6 vs.244.6±4.9,138.5±6.7 vs.210.9±10.0;both P＜0.05),the average integral optical density values of P53,PUMA and BAX proteins were significantly increased(156.8±11.6 vs.93.5±11.6,151.3±3.3 vs.38.0±4.0,87.0±5.0 vs.38.4±5.5;all P＜0.05),the relative expression levels of Sirt1 and Bcl-2 proteins were significantly decreased(0.51±0.07 vs.0.74±0.07,0.36±0.03 vs.0.53±0.05;both P＜0.05),and the relative expression levels of P53,PUMA and BAX proteins were significantly increased(0.37±0.06 vs.0.21±0.02,0.62±0.06 vs.0.23±0.02,1.08±0.06 vs.0.45±0.03;all P＜0.05).(3)Compared with the model group,the hippocampal tissue structure of the high-dose and low-dose TAC groups was relatively compact and uniform,the neurons were neatly arranged,and the cell structure was relatively clear and complete,while the number of neuronal apoptotic cells and the apoptosis rate decreased significantly(respectively[3.8±0.7]cells vs.[6.2±1.2]cells,[12.4±2.8]％vs.[20.2±3.9]％;both P＜0.05),and the average integrated optical density values of the positive expression areas of Sirt1 and Bcl-2 proteins(the high-dose and low-dose TAC groups:Sirt1 150.0±4.8,131.3±1.3,and Bcl-2 207.1±7.4,169.5±3.9,respectively)were significantly increased(both P＜0.05),the average integral optical density values of P53,PUMA and BAX proteins were significantly decreased(the high-dose and low-dose TAC groups:P53 105.9±8.8,115.5±9.0,and PUMA56.8±5.1,74.4±3.9,and BAX40.5±5.6,48.4±5.0,respectively,all P＜0.05),the relative expression levels of Bcl-2 protein(the high-dose and low-dose TAC groups:0.53±0.05,0.47±0.02,respectively)were significantly increased(P＜0.05),the relative expression levels of P53(the high-dose and low-dose TAC groups:0.21±0.02,0.24±0.04,respectively),PUMA(the high-dose and low-dose TAC groups:0.36±0.02,0.28±0.04,respectively)and BAX proteins(the high-dose and low-dose TAC groups:0.52±0.02,0.54±0.03,respectively)were significantly decreased(all P＜0.05),the relative expression level of Sirt1 protein in the TAC high-dose group was significantly decreased(0.71±0.05,P＜0.05),and the relative expression level of Sirt1 protein in the TAC low-dose group was not statistically significant(0.52±0.08,P＞0.05).Conclusion TAC can alleviate neuronal damage and reduce the apoptosis rate of neurons in the hippocampus of CCH rats,and the mechanism may be related to the activation of Sirt1/P53 pathway,inhibition of P53 protein activity,and thus the expression level of apoptosis-related proteins in the downstream of TAC.

Background: Crawling-type gastric adenocarcinoma is a rare subtype of gastric cancer, however, the understanding on this special entity of gastric cancer is still lacking. Aims: To investigate the clinical, endoscopic and pathological characteristics of crawling-type early gastric adenocarcinoma. Methods: Patients diagnosed as crawling-type early gastric adenocarcinoma in Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were recruited consecutively in a retrospective study. The clinical data were reviewed, the pathological specimens were collected for immunohistochemical staining, and a telephone follow-up was conducted for prognosis analysis. Results: Fourteen patients with crawling-type early gastric adenocarcinoma and fulfilling the inclusion criteria were enrolled in the study, of them, 9 were male, 5 were female, and the mean age was 65.9 years old. No family history of gastric cancer was reported. The clinical manifestations were not specific. All patients were positive for Helicobacter pylori (Hp) infection. Tumors were more likely to occur in the middle and lower thirds of the stomach, with marked atrophic background mucosa. Macroscopically, 11 lesions were superficial-depressed (0-IIc) and 3 were superficial-flat type (0-IIb+ IIc). The color of the lesions was red. Lesions with indistinct border were observed endoscopically in 10 cases. Complete resection was achieved in all 14 patients after endoscopic submucosal dissection n=10 or surgical treatment n=4. Three submucosal and 11 intramucosal infiltration were observed pathologically. Immunohistochemical results of gastric (MUC5AC and MUC6) and intestinal (MUC2, CD10 and CDX-2) markers showed that most of the patients were mixed immunophenotype; the Ki-67 index ranged mostly between 30% and 70%. In a mean follow-up time of 38 months, all 14 patients were survived. Two patients with heterochronous early gastric cancer were found by follow-up endoscopy. Conclusions: When a superficial-depressed or superficial-flat type tumor with reddish color change and atrophic background mucosa is observed endoscopically in an Hp-positive patient, the possibility of crawling-type early gastric adenocarcinoma should be considered. Adequate preoperative evaluation should be carried out to judge the extent and depth of tumor invasion, which may guide the decision of treatment strategy. Postoperative endoscopic surveillance is recommended.

Objective:To discuss the safety and curative effect of transurethral plasmakinetic enucleation of prostate(TUKEP) in the treatment of large-volume prostate hyperplasia.Methods:From October 2015 to April 2017, the clinical data of 126 patients with large-volume prostate hyperplasia(weight of prostate>80 g) who admitted to Yuncheng Central Hospital were retrospectively analyzed.Different enucleation methods were used according to weight of prostate: ball enucleation for 80~120 g prostate; divided enucleation for more than 120 g prostate.The clinical data were analyzed and summarized.Results:All 126 patients completed operation successfully.The mean enucleation time, cutting time upon harvesting, intraoperative blood loss and intraoperative mean weight of prostate removed of the 126 patients were (19.4±2.4)min, (61.9±16.7)min, (65.3±47.5)mL and (104.5±23.1)g, respectively.Five cases of them had capsule perforation during operation and indwelling catheter for one week after operation, and unobstructed micturition was recovered after removing the urinary catheter, with no repeated hemorrhage or urinary tract infection.Seven cases received intra-operative blood transfusion, with no transurethral resection syndrome(TURS) during and after operation.These patients were followed up for 1~6 months, 23 cases lost to follow up and 14 cases suffered from temporary urinary incontinence.They received health education and levator ani training and were able to completely control urination during follow-up.The IPSS score, QOL score, Qmax and PVR of the patients after operation were (7.6±1.4)points, (1.7±0.6)points, (20.2±3.1)mL/s and (15.0±9.3)mL, respectively, which showed statistically significant differences compared with before operation( t=15.712, 18.331, -21.382 and 16.380, all P<0.001). All of these indicators were obviously improved than before operation, but there was no statistically significant difference in normal ejaculation before and after operation( P=0.252). Conclusion:TUKEP can radically remove prostate tissue and is an effective and safe surgical method in the treatment of large-volume prostate hyperplasia.

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor β1 (TGF-β1) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (ATRvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-β1-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-β1 reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory κB kinase 16 (IKK 16), which is known to inhibit the NF-κB pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-β1-induced EndMT, but it had no effect on TGF-β1-induced EndMT alone. Smad7, which is a key regulator of TGF-β/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-β1-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.
Actins ; Endothelial Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation ; Oxidative Stress* ; Permeability ; Phosphotransferases ; Transforming Growth Factors ; Umbilical Veins ; Vimentin