Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

Objective:To explore the optimal blood glucose-lowering strategies for patients with diabetic ketoacidosis (DKA) to enhance personalized treatment effects using machine learning techniques based on the United States Critical Care Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ).Methods:Utilizing the MIMIC-Ⅳ database, the case data of 2 096 patients with DKA admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center from 2008 to 2019 were analyzed. Machine learning models were developed, and receiver operator characteristic curve (ROC curve) and precision-recall curve (PR curve) were plotted to evaluate the model's effectiveness in predicting four common adverse outcomes: hypoglycemia, hypokalemia, reductions in Glasgow coma scale (GCS), and extended hospital stays. The risk of adverse outcomes was analyzed in relation to the rate of blood glucose decrease. Univariate and multivariate Logistic regression analyses were conducted to examine the relationship between relevant factors and the risk of hypokalemia. Personalized risk interpretation methods and predictive technologies were applied to individualize the analysis of optimal glucose control ranges for patients.Results:The machine learning models demonstrated excellent performance in predicting adverse outcomes in patients with DKA, with areas under the ROC curve (AUROC) and 95% confidence interval (95% CI) for predicting hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stays being 0.826 (0.803-0.849), 0.850 (0.828-0.870), 0.925 (0.903-0.946), and 0.901 (0.883-0.920), respectively. Analysis of the relationship between the rate of blood glucose reduction and the risk of four adverse outcomes showed that a maximum glucose reduction rate > 6.26 mmol·L -1·h -1 significantly increased the risk of hypoglycemia ( P < 0.001); a rate > 2.72 mmol·L -1·h -1 significantly elevated the risk of hypokalemia ( P < 0.001); a rate > 5.53 mmol·L -1·h -1 significantly reduced the risk of GCS score reduction ( P < 0.001); and a rate > 8.03 mmol·L -1·h -1 significantly shortened the length of hospital stay ( P < 0.001). Multivariate Logistic regression analysis indicated significant correlations between maximum bicarbonate levels, blood urea nitrogen levels, and total insulin doses with the risk of hypokalemia (all P < 0.01). In terms of establishing personalized optimal treatment thresholds, assuming optimal glucose reduction thresholds for hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stay were x1, x2, x3, x4, respectively, the recommended glucose reduction rates to minimize the risks of hypokalemia and hypoglycemia should be ≤min{ x1, x2}, while those to reduce GCS score decline and extended hospital stay should be ≥ max{ x3, x4}. When these ranges overlap, i.e., max{ x3, x4} ≤ min{ x1, x2}, this interval was the recommended optimal glucose reduction range. If there was no overlap between these ranges, i.e., max{ x3, x4} > min{ x1, x2}, the treatment strategy should be dynamically adjusted considering individual differences in the risk of various adverse outcomes. Conclusion:The machine learning models shows good performance in predicting adverse outcomes in patients with DKA, assisting in personalized blood glucose management and holding important clinical application prospects.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

OBJECTIVE To explore the antitumor effect and mechanism of total alkaloids of Gelsemium elegans （TA） and sempervirine （SPV） in vitro. METHODS The effects of low， medium and high concentrations of TA （50， 100， 200 μg/mL） and SPV （10， 30， 50 μmol/L） on the morphology of human hepatoma cells （HepG2， Bel-7402）， human lung cancer cells （A549） and human colon cancer cells （HCT-8） were observed， and the toxicity of TA and SPV to four tumor cells was monitored. The effects of TA and SPV on the contents of caspase-3 and caspase-9 in the supernatant of HCT-8 cells， the protein expressions of phosphorylated protein kinase B （p-Akt） （Thr308， Ser473）， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， survivin， C/EBP-homologous protein （CHOP）， immunoglobulin binding protein （Bip） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） in HCT-8 cells were detected. RESULTS After the intervention of TA and SPV， the volume reduction and nuclear shrinkage were founded in four tumor cells； the cell activity decreased to varying degrees， among which TA and SPV had the best inhibitory effect on HCT-8 cells. After the intervention of TA and SPV， the contents of caspase-3 and caspase-9 in the supernatant of HCT-8 cells， the protein expressions of Bax， CHOP， Bip and LC3Ⅱ all increased to different degrees， while the protein expressions of p-Akt （Thr308， Ser473）， Bcl-2 and survivin in HCT-8 cells all decreased to different degrees. CONCLUSIONS TA and SPV have inhibitory effects on the above four tumor cells， and the inhibitory effect on HCT-8 cells is the best. The mechanism of their action on HCT-8 cells may be related to promoting apoptosis， activating endoplasmic reticulum stress and autophagy.

Objective : To explore the relationship between geriatric nutritional risk index( GNRI) and perioperative nutritional status，postoperative recovery and complications in elderly patients with gastric cancer． Methods : In this retrospective study，212 elderly patients ( aged ≥60 years ) with gastric cancer who underwent gastrectomy were recruited．GNRI was used to retrospectively assess the patients' preoperative nutritional status ，and analyze the relationship between GNRI and perioperative nutritional status，postoperative recovery and complications．The ROC curve was applied to explore the value of GNRI in predicting postoperative complications. Results : The inci- dence of preoperative nutritional risk in elderly patients undergoing gastric cancer surgery was 45. 07%．Compared with the patients whose GNRI＞98 points，the patients whose GNRI≤98 points had different degrees of decrease in serum total protein，albumin，prealbumin，hemoglobin and lymphocyte counts before surgery，day 1 and day 5－8 after surgery (P ＜0. 05) ．The patients whose GNRI ＜92 points had longer postoperative hospital stay than those with GNRI＞98 points (P＜0. 05) ．With the decrease of GNRI scores，the incidence of complications showed an upward trend(P＜0. 001) ．The multivariate analysis of the relationship between GNRI and postoperative complica- tions showed that TNM staging of III －IV and GNRI ＜92 points were independent risk factors for complications. GNRI had a good predictive value for the occurrence of complications (AUC = 0. 639，95% CI : 0. 570－0. 703，P = 0. 001，Cut-off value : 92. 21) ． Conclusion GNRI can be used for preoperative nutritional assessment for eld- erly gastric cancer patients．Patients with GNRI＜92. 21 points should be actively given nutritional therapy to im- prove perioperative nutritional status，speed up postoperative recovery，and reduce the occurrence of complications.

Objective:To explore the application effect of the co-management care intervention model based on mobile platform in home care of elderly patients after hip fractures.Methods:A total of 108 elderly patients who underwent hip arthroplasty in Department of Orthopedics of Fengxian District Central Hospital of Shanghai from June 2020 to February 2021 were selected by the convenient sampling method. According to random number table method, they were randomly divided into the control group and the observation group, with 54 cases in each group. After discharge, the control group received routine out-of-hospital care management, while the observation group received mobile platform based co-managed care home care management for 12 weeks. The hip function (Harris score) , activities of daily living (MBI score) , nutrition, quality of life (EQ-5D score) and incidence of complication were compared between the two groups.Results:Harris score, MBI score and serum albumin level of observation group after intervention were higher than those before intervention and EQ-5D score was lower than before intervention, and the differences were statistically significant ( P<0.05) . The Harris score and MBI score of the control group after the intervention were higher than those before the intervention, and the differences were statistically significant ( P<0.05) . After the intervention, the Harris score, MBI score and serum albumin level of the observation group were higher than those of the control group and the EQ-5D score was lower than that of the control group, and the differences were statistically significant ( P<0.05) . The total incidence of complications in the observation group and the control group were respectively 7.41% (4/54) and 31.48% (17/54) , and the difference was statistically significant (χ 2=9.990, P=0.002) . Conclusions:In the post-operative home care management of elderly hip fractures, the implementation of the co-management care model based on the mobile platform can effectively improve the hip function, nutrition and quality of life of patients, improve ability of daily living and reduce the occurrence of complications.

Objective:To evaluate the efficacy of stem cell transplantation in treatment of ischemic stroke.Methods:Randomized controlled studies about stem cell transplantation in the treatment of ischemic stroke were searched from Pubmed, Cochrane Library, Embase, Ovid, China National Knowledge Infrastructure (CNKI), Wanfang and VIP database from database establishment to March 2021. The literature was screened according to the inclusion and exclusion criteria and the clinical data of the stem cell transplantation patients and conventional treatment patients were extracted. The differences of baseline value and final value of National Institutes of Health Stroke Scale (NIHSS) scores, Function Independent Measurement (FIM) scores, Fugl-Meyer Measurement (FMA) scores, Barthel index (BI), Activity of Daily Living (ADL) scale scores, modified Rankin scale (mRS) scores between the two groups were combined for Meta analysis.Results:Eighteen articles were included in the study, including 1334 patients; 668 patients were from the stem cell transplantation group and 666 patients were from the conventional treatment group. The results showed that NIHSS scores (difference in means [ MD]=3.510, 95%CI: 2.540-4.480, P=0.000], FIM scores ( MD=11.380, 95%CI: 5.470-17.280, P=0.000), FMA scores ( MD=13.830, 95%CI: 12.590-15.070, P=0.000), BI ( MD=22.100, 95%CI: 19.430-24.770, P=0.000), ADL scores ( MD=9.290, 95%CI: 3.530-15.050, P=0.002), and mRS scores ( P=0.004) in the stem cell transplantation group were significantly higher as compared with those in the conventional treatment group ( P<0.05). Conclusion:Stem cell transplantation on the basis of conventional treatment has good clinical efficacy in the recovery of neurological function, improvement of activity of daily living, and improvement of limb motor function in patients with ischemic stroke.

Objective:To make the early clinical antibiotic regimen by finding out the infection of corynebacterium in the pus of patients with granulomatous mastitis in the early stage.Methods:A total of 42 patients who were diagnosed and treated in the Breast Center of Guangdong Maternal and Child Health Hospital from Jun. 2016 to Mar. 2017 with complete follow-up data were retrospectively analyzed. PCR method was used to detect corynebacterium in the patients’ pus. Patients in the positive group were treated with antibiotics alone, antibiotics + hormones and hormones alone, while patients in the negative group were treated with antibiotics + hormones and hormones alone. The postoperative recurrence rate and cure rate of different groups of patients were observed.Results:The antibiotic regimen for granulomatous mastitis in patients with corynebacterium infection included a combination of short-acting levofloxacin and azithromycin and long-acting anti-mycobacterium drugs. Among the 42 patients in the subgroup, 21 patients were confirmed positive for corynebacterium by PCR detection of pus, and the postoperative recurrence rate was 23.5%. There was a statistically significant difference between the antibiotic group, the antibiotic + hormone group and the hormone group in treatment of granulomatous mastitis infected with corynebacterium ( χ2=5.494, P=0.036) . PCR detection shouwed corynebacterium negative in 21 cases, and postoperative recurrence rate of 16.7%. No statistically significant difference in efficacy was found between antibiotic + hormone group and hormone only group for GM patients without bacterial infection ( χ2=1.129, P=0.719) . Conclusion:Early detection of corynebacterium infection in GM patients is significant for clinical guidance of the application of lipophilic antibiotics.

Objective To investigate alterations of blood perfusion in subcortical regions in patients with Parkinson′s disease (PD) by three dimentional arterial spin labeling (ASL) magnetic resonance imaging (MRI). Methods Thirty patients with PD and 40 control subjects were recruited from the inpatient and outpatient of the Department of Neurology of Northern Jiangsu People′s Hospital during October 2014 to October 2016, and routine brain MRI and 3D pseudo?continuous pulse ASL were performed on all the subjects. The cerebral blood flow (CBF) maps derived from 3D ASL were coregistered to the Montreal Neurological Institute brain space. The stereo?templates of bilateral caudate nucleus, putamen nucleus, globus pallidum and thalamus from Anatomical Automatic Labeling were used as region of interest (ROI) to exstract absolute CBF values in these subcortical regions, respectively. The CBF ratio (rCBF) values represented by individual whole brain CBF divided by each of the regional CBF were also calculated in consideration of the difference between individual whole brain CBF. The CBF and rCBF values were compared respectively between groups by one?way analysis of variance. Results The subcortical CBF values (ml·100 g-1·min-1) for each ROI in PD (caudate nucleus (left: 35.32±6.47, right: 36.17±7.07), globus pallidum (left: 40.42 ± 5.83, right: 40.18 ± 5.70), putamen nucleus (left: 41.97 ± 6.12, right: 42.91 ± 6.43) and thalamus (left: 46.58 ± 7.71, right: 49.11 ± 7.10)) were significantly lower than that in the control group (caudate nucleus (left: 41.38±7.05,right: 41.63±6.85), globus pallidum (left: 45.65±8.35,right: 45.53±8.94), putamen nucleus (left: 48.49±8.78, right: 48.99±8.88) and thalamus (left: 54.32±11.94,right: 56.21±11.98), F=13.58, 10.56, 12.11, 10.06, 8.59, 8.23, 9.57, 8.30, P=0.000, 0.002, 0.005, 0.005, 0.001, 0.002, 0.003, 0.005, respectively ). The whole brain mean CBF values of each subject were also extracted and compared bewteen groups, and mean CBF values (ml·100 g-1·min-1) in PD patients (42.14±9.61) decreased significantly than those in the control group (51.59±9.67, F=16.42, P<0.01), and there was a 18.31% decrement in whole brain mean CBF in the patient group. However, rCBF values for almost all subcortical ROIs of the patients significantly increased when compared with the control group. Conclusions The decreased absolute cerebral blood perfusion involved not only subcortical regions, but also the whole brain level in the course of PD. The CBF metabolism in patients with PD may have been redistributed, with relative hyperperfusion in the subcortical brain regions contrast to the whole brain perfusion level of patients themselves.

ObjectiveTo investigate the value of combined measurement of serum alpha-fetoprotein (AFP), Dickkopf-1 (DKK1), and cytoskeleton-associated protein 4 (CKAP4) in the diagnosis of hepatocellular carcinoma (HCC). MethodsA total of 122 patients with HCC (76 patients in the early stage), 152 patients with liver cirrhosis, and 105 patients with chronic hepatitis B, who were admitted to The First Affiliated Hospital of Soochow University from January 2013 to December 2017, were enrolled, and 101 individuals who underwent physical examination during the same period of time were enrolled as healthy control group. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between multiple groups. A binary logistic regression analysis was used to obtain the new variable of predicted probability, and the receiver operating characteristic (ROC) curve analysis was performed for each index and predicted probability to investigate the area under the ROC curve (AUC), sensitivity, and specificity of the three indices used alone or in combination. ResultsThe HCC group had significantly higher serum levels of AFP, DKK1, and CKAP4 than the liver cirrhosis group, the chronic hepatitis B group, and the healthy control groups (F=121.618, 84.559, and 91.769, P＜0.001). The combination of AFP, DKK1, and CKAP4 had an AUC of 0.967 (95% confidence interval ［CI］: 0.950-0.984), a sensitivity of 0.869, and a specificity of 0.980, which were significantly higher than the AUCs, sensitivities, and specificities of the three indices used alone (all P＜0.05). The combination of the three indices had an AUC of 0.965 (95%CI: 0.942-0.988), a sensitivity of 0.868, and a specificity of 0.980 in the diagnosis of early-stage HCC, which were significantly higher than the AUCs, sensitivities, and specificities of the three indices used alone (all P＜0.05). ConclusionCombined measurement of serum AFP, DKK1, and CKAP4 improves the accuracy, sensitivity, and specificity of HCC diagnosis and thus has an important clinical value in the screening for and early diagnosis of HCC.