Objective To investigate the effects of Buyang Huanwu Decoction on nerve regeneration after cerebral ischemia in mice based on Cav-1/Notch1/Hes1 signaling pathway.Methods Wild(WT)and Cav-1-/-(KO)male mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group,with 10 mice in each group.The middle cerebral artery occlusion method was used to construct the mouse cerebral ischemia model.After modeling,5-ethynyl-2'-deoxyuridine(EdU)was injected intraperitoneally every 7 days for 3 times(with an interval of 8 hours).Buyang Huanwu Decoction group was given 18.5 g/kg Buyang Huanwu Decoction by gavage daily,while the sham-operation group and model group were given distilled water of equal volume by gavage for 21 consecutive days.The neurological function of mice was evaluated using modified neurological severity score,brain tissue morphology was observed through HE staining,nerve regeneration in the ischemic side injury area was detected using dual immunofluorescence staining,Western blot was used to detect the expressions of Notch1 and Hes1 protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurological function score of the mice in the WT and KO model groups significantly increased(P<0.01),the arrangement of neurons in the ischemic cortical area was disordered,with nucleoli shrinking,marginalization,and even rupture,widened intercellular spaces,intracellular edema and vacuolar changes,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area significantly increased(P<0.01).Compared with the same genotype model group,the neurological function score of the WT and KO Buyang Huanwu Decoction group significantly decreased(P<0.01),the neurons in the ischemic cortical area were arranged neatly and structurally intact,with reduced intercellular space and clear nucleoli,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area was significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area were significantly decreased(P<0.01).Compared with the corresponding WT group,the neurological function scores of mice in the KO model group and KO Buyang Huanwu Decoction group significantly increased(P<0.01),the neurons in the ischemic cortical area had more severe nucleolar condensation,marginalization and rupture,with more vacuolar changes and ischemic injury,the co-localization of EdU/Nestin and EdU/NeuN in the ischemic side injury area was significantly decreased(P<0.01),and the expression of Notch1 and Hes1 proteins in ischemic cortical area significantly increased(P<0.01).Conclusion Buyang Huanwu Decoction can promote nerve regeneration after cerebral ischemia,which may be related to the regulation of Cav-1 thereby inhibition Notch1//Hes1 signaling pathway activity.

Objective To investigate the effects of Buyang Huanwu Decoction on nerve regeneration after cerebral ischemia in mice based on Cav-1/Notch1/Hes1 signaling pathway.Methods Wild(WT)and Cav-1-/-(KO)male mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group,with 10 mice in each group.The middle cerebral artery occlusion method was used to construct the mouse cerebral ischemia model.After modeling,5-ethynyl-2'-deoxyuridine(EdU)was injected intraperitoneally every 7 days for 3 times(with an interval of 8 hours).Buyang Huanwu Decoction group was given 18.5 g/kg Buyang Huanwu Decoction by gavage daily,while the sham-operation group and model group were given distilled water of equal volume by gavage for 21 consecutive days.The neurological function of mice was evaluated using modified neurological severity score,brain tissue morphology was observed through HE staining,nerve regeneration in the ischemic side injury area was detected using dual immunofluorescence staining,Western blot was used to detect the expressions of Notch1 and Hes1 protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurological function score of the mice in the WT and KO model groups significantly increased(P<0.01),the arrangement of neurons in the ischemic cortical area was disordered,with nucleoli shrinking,marginalization,and even rupture,widened intercellular spaces,intracellular edema and vacuolar changes,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area significantly increased(P<0.01).Compared with the same genotype model group,the neurological function score of the WT and KO Buyang Huanwu Decoction group significantly decreased(P<0.01),the neurons in the ischemic cortical area were arranged neatly and structurally intact,with reduced intercellular space and clear nucleoli,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area was significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area were significantly decreased(P<0.01).Compared with the corresponding WT group,the neurological function scores of mice in the KO model group and KO Buyang Huanwu Decoction group significantly increased(P<0.01),the neurons in the ischemic cortical area had more severe nucleolar condensation,marginalization and rupture,with more vacuolar changes and ischemic injury,the co-localization of EdU/Nestin and EdU/NeuN in the ischemic side injury area was significantly decreased(P<0.01),and the expression of Notch1 and Hes1 proteins in ischemic cortical area significantly increased(P<0.01).Conclusion Buyang Huanwu Decoction can promote nerve regeneration after cerebral ischemia,which may be related to the regulation of Cav-1 thereby inhibition Notch1//Hes1 signaling pathway activity.

Objective:To evaluate the effects of adipose-derived stem cells (ADSCs) and ADM microparticle on diabetic wound healing.Methods:ADSCs was co-cultured with ADM microparticle in vitro. The models of diabetic nude mice were established by intraperitoneal injection of STZ and the full-thickness skin defects were designed on the back. All 24 diabetic mice were randomly divided into 4 group: experimental groups were transplanted with ADSCs and ADM microparticle and the other groups were transplanted with ADSCs, ADM microparticle and blank control group was set up. On the 7th and 14 th days, the wound healing rate of 3 mice randomly selected from each group was calculated, and the thickness between dermis and epidermis was measured by hematoxylin and eosin staining. The density of neovascularization was measured by immunohistochemical staining. The differences were compared between the groups.Results:Compared to the ADSCs groups, the mice of the experimental groups showed higher cell survival rate. The wound healing rate in the experimental groups was (86.0±2.7)% (7 days) and (98.5±1.1)% (14 days), thicker dermis-epidermis distance was (99.1±1.8) μm (7 days) and (124.3±4.3) μm (14 days) ( P<0.05), and higher density of neovascularization was noted. Conclusions:The transplantation with active ADM microparticle can significantly promote neovascularization and wound healing of diabetic wound.

Objective::Older patients with comorbidity, such as coronary heart disease (CHD) and malignant gastrointestinal tumors, are at a high risk of bleeding events. However, risk prediction models based on risk factor assessment remain unclear. This study aimed to establish an individualized bleeding risk assessment system based on the analysis of 10-year inpatient clinical big data.Methods::Total clinical data of 56,819 patients with CHD and 25,988 patients with malignant digestive tract tumors (admitted from January 2008 to December 2017) were retrospectively collected at the First and Second Medical Centers of Chinese People’s Liberation Army General Hospital. Among them, 1307 patients with CHD and malignant digestive tract tumors were screened as the derivation cohort. The dependent variable was the occurrence of major clinical bleeding events. Baseline statistics and hypothesis tests of differences were performed for independent variables according to the occurrence of bleeding. Decision Tree, eXtreme Gradient Boosting (XGBoost), logistic regression, and random forest models were used for comparison. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC-ROC) were applied as the criteria for evaluating and verifying model performance. To evaluate this developed model, another cohort comprising 454 patients (admitted from January 2018 to December 2019) was prospectively enrolled as the validation cohort based on the same inclusion and exclusion criteria.Results::Among the 64 variables with <50% missing values, the recursive feature elimination method with a random forest model was used to screen the selected variables. The highest accuracy was obtained following the selection of 10 scalars, and the final model was constructed accordingly. XGBoost demonstrated the best performance comprehensively. The AUC-ROC of this model was 0.981, with an accuracy, sensitivity, and specificity of 0.939, 0.950, and 0.927, respectively. In the validation cohort, the AUC-ROC, accuracy, sensitivity, and specificity of the XGBoost model were 0.702, 0.718, 0.636, and 0.725, respectively. The rate of major bleeding events has a positive correlation with the bleeding risk score quintiles. To allow for convenient clinical application, a smartphone application was developed for easy access and calculation (http://fir.master-wx.com/sghr).Conclusion::We successfully established a risk model and score for predicting bleeding events in older patients with comorbidity, such as CHD and gastrointestinal cancer.

Objective::Older patients with comorbidity, such as coronary heart disease (CHD) and malignant gastrointestinal tumors, are at a high risk of bleeding events. However, risk prediction models based on risk factor assessment remain unclear. This study aimed to establish an individualized bleeding risk assessment system based on the analysis of 10-year inpatient clinical big data.Methods::Total clinical data of 56,819 patients with CHD and 25,988 patients with malignant digestive tract tumors (admitted from January 2008 to December 2017) were retrospectively collected at the First and Second Medical Centers of Chinese People’s Liberation Army General Hospital. Among them, 1307 patients with CHD and malignant digestive tract tumors were screened as the derivation cohort. The dependent variable was the occurrence of major clinical bleeding events. Baseline statistics and hypothesis tests of differences were performed for independent variables according to the occurrence of bleeding. Decision Tree, eXtreme Gradient Boosting (XGBoost), logistic regression, and random forest models were used for comparison. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC-ROC) were applied as the criteria for evaluating and verifying model performance. To evaluate this developed model, another cohort comprising 454 patients (admitted from January 2018 to December 2019) was prospectively enrolled as the validation cohort based on the same inclusion and exclusion criteria.Results::Among the 64 variables with <50% missing values, the recursive feature elimination method with a random forest model was used to screen the selected variables. The highest accuracy was obtained following the selection of 10 scalars, and the final model was constructed accordingly. XGBoost demonstrated the best performance comprehensively. The AUC-ROC of this model was 0.981, with an accuracy, sensitivity, and specificity of 0.939, 0.950, and 0.927, respectively. In the validation cohort, the AUC-ROC, accuracy, sensitivity, and specificity of the XGBoost model were 0.702, 0.718, 0.636, and 0.725, respectively. The rate of major bleeding events has a positive correlation with the bleeding risk score quintiles. To allow for convenient clinical application, a smartphone application was developed for easy access and calculation (http://fir.master-wx.com/sghr).Conclusion::We successfully established a risk model and score for predicting bleeding events in older patients with comorbidity, such as CHD and gastrointestinal cancer.

Objective A database of normal people's external nose was established through 3D measurement. This database was used to customize the external nose for patients with nasal defects and to assist the operator to carry out the whole nose reconstruction surgery, so as to carry out the postoperative evaluation.Methods 3D scanning of the subject's face, measurement of relevant indexes of the nose and establishment of a database, the operator used normal nose database to customize the customized external nose for 17 patients with nasal defects, assisted them in the whole nose reconstruction surgery, and used independent sample t test for data statistics to evaluate the expected effect of surgery. Results There was no statistically significant differences between the postoperative actual data and the preoperative personalized data (P> 0.05) in right root wing distance, left root wing distance, nose length, nasal base width, nose width, right side vertical bisect nasal line, left side vertical bisect nasal line, nose height, medial malleolus spacing, face width, mouth split width, facial height, nasal width index, nasal width index, interondylar-nasal width index and nasal high index. The actual data of nasal deep was statistically different from preoperative personalized data (P < 0.05). Conclusions Analysis showed no significant difference between the actual data nasal surgery and preoperative customization data. 3D measurement of normal human external nasal establishment database to customize the external nose for patients with nasal defects, can assist the surgeon to perform total nasal reconstruction surgery and improve predictability and make surgery more precise. Postoperative assessments can also be performed to compare preoperative and postoperative outcomes.

Objective To explore the clinical characteristics of renal transplantation in patients with diabetes mellitus (DM)-induced end-stage nephropathy.Methods The clinical data of 408 cases who underwent renal transplantation in our center from 2009 to 2013 were retrospectively analyzed.The patients were divided into DM group (n =82) and non-DM group (n =326).The postoperative infection,delayed graft function (DGF),adverse events,and the survival rate of patients/kidneys were comparatively analyzed.Results The incidence of postoperative infection,DGF and adverse events was significantly higher in DM group than in non-DM group (23.2％ vs.15.6％,P =0.04;17.1％ vs.8.6 ％,P =0.04;13.4％ vs.8.3 ％,P =0.03).No significant difference was found in the 1-,2-,and 3-year survival rate of patients and kidneys between the two groups after operation (P＞ 0.05).Conclusion The incidence of postoperative infection,DGF and adverse events is higher in DM patients.The DM does not affect the survival rate of patients/kidneys through appropriate treatment.It is important to prevent complications in DM patients after renal transplantation.

Objective To study the effect of electrical stimulation of the fastigial nucleus of the cerebellum (FNS) on learning,memory and the expression of growth-association protein-43 (GAP-43) after cerebral ischemia and reperfusion.Methods Sixty healthy,adult,male Sprague-Dawley rats were randomly divided into a normal group,a sham-operation group (sham group),a model group and an FNS group,with 15 rats in each.Left middle cerebral artery occlusion and reperfusion (MCAO/R) was administered to the rats in the FNS and model groups using the thread embolism method.The rats of the FNS group were given FNS treatment using a pair of needle electrodes inserted into the cerebellar fastigial nucleus 3hrs after the MCAO/R.Needle electrodes were similarly inserted in the model group rats,but no electrical stimulus was applied.Then the rats' learning and memory abilities were tested using a Morris water maze on days 1,3 and 7 after the MCAO/R modeling.The expression of GAP-43 mRNA on the side of the cerebral infarction was detected using a quantitative,real-time polymerase chain reaction.Results The average escape]atencies of the rats in the model and FNS groups were significantly longer than those of the normal and sham groups at all time points,but the FNS group rats demonstrated a significantly shorter average escape latency than the rats of the model group at each time point.The normal and sham groups showed a significantly lower expression of GAP-43 mRNA than the model and FNS group rats at all time points.The FNS group rats had a significantly higher level of GAP-43 mRNA than the rats of the model group.Conclusion FNS improved the rats' learning and memory abilities.This might be associated with the up-regulation of GAP-43 mRNA in neurons on the side of the cerebral infarction which could promote the regeneration and repair of peripheral nerve axons in the area of the infarction.

INTRODUCTIONWe compared the agreement of diabetic retinopathy (DR) assessment between trained non-physician graders (NPGs) and family physicians (FPs) in a primary healthcare setting.

METHODSThis was a cross-sectional study conducted retrospectively over a period of one month. The participants were diabetic patients from two primary healthcare clinics (polyclinics) in Singapore. Single-field digital retinal images were obtained using a non-mydriatic 45-degree fundus camera. Retinal images were graded for the presence or absence of DR by FPs at the polyclinics and by NPGs at a central ocular grading centre. The FPs' and NPGs' assessments of DR were compared with readings by a single retinal specialist (reference standard).

RESULTSA total of 367 diabetic patients (706 eyes) were included in the study. The mean age of the patients was 63 years, and the majority were Chinese (83.8%). For DR assessment, the agreement between NPGs and the retinal specialist was substantial (ĸ = 0.66), while the agreement between FPs and the retinal specialist was only fair (ĸ = 0.40). NPGs' assessment showed higher sensitivity (70% vs. 45%) and comparable specificity (94% vs. 92%) as compared to FPs' assessment. The area under the receiver operating characteristic curve of NPGs' assessment of DR was greater than that of the FPs' (0.82 vs. 0.69, p < 0.001).

CONCLUSIONThis study has demonstrated that trained NPGs are able to provide good detection of DR and maculopathy from fundus photographs. Our findings suggest that DR screening by trained NPGs may provide a costeffective alternative to FPs.

Aged ; Cross-Sectional Studies ; Diabetic Retinopathy ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Mydriatics ; Nurses ; Observer Variation ; Ophthalmology ; manpower ; Physicians, Family ; Primary Health Care ; methods ; ROC Curve ; Referral and Consultation ; Reproducibility of Results ; Sensitivity and Specificity ; Singapore