1.Effects of sensory and motor nerve homogenates at different concentrations on proliferation and osteogenesis differentiation of bone marrow mesenchymal stem cells
Huijie JIANG ; Junqin LI ; Jimeng WANG ; Donglin LI ; Pengzhen CHENG ; Yi GAO ; Chunmei WANG ; Liu YANG ; Guoxian PEI
Chinese Journal of Orthopaedic Trauma 2017;19(2):151-156
Objective To investigate the effect of sensory and motor nerve homogenates at different concentrations on the proliferation and osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) in rats.Methods The saphenous nerve and the muscle branch of the sciatic nerve in rats were extracted surgically as sensory and motor nerve tissues,respectively.The primary nerve homogenates (10 mg/mL) were prepared as per 10 mg tissue with 1 mL osteoblast inducing conditional media,and 10 times diluted after filtration purification to prepare sensory and motor nerve homogenates at concentration gradients of 1.0,0.1,0.01,0.001 and 0.0001 mg/mL.Cultivation GFP ± rat pups BMSCs in vitro were trained to P3 generation.The experiment was carried out in 3 groups.The sensory and motor nerve homogenates of 500 μL at the above 6 concentration gradients were added during cultivation respectively in the sensory nerve group (n =18) and the motor nerve group(n =18) while 500 μL of osteoblast inducing conditional media was added in the control group(n =3).Cell proliferation quantity detection and alkaline phosphatase (ALP) staining were used to assess the proliferation and differentiation of BMSCs after 14 days.Results According to the results of CCK-8,the cellular absorbance values at concentrations of 1.0 and 0.1 mg/mL homogenate in the sensory nerve group (1.957 ±0.065 and 1.751±0.073) were significantly greater than in the control group (1.145±0.087) while the cellular absorbance value at concentration of 10.0 mg/mL homogenate in the motor nerve group (0.304 ± 0.619) was significandy smaller than in the control group (1.145 ± 0.087) (P < 0.05).According to the ALP staining,the amounts of cellular calcium nodules in the sensory and motor nerve groups (2.667 ± 0.816 and 3.000 ± 0.632,respectively) were significantly smaller than in the control group (11.833 ± 1.471) (P < 0.05).Conclusion Sensory nerve homogenate is different from motor nerve homogenate in that it may promote proliferation of BMSCs and inhibit osteogenesis differentiation of BMSCs in a certain rage of concentrations.
2.Prevascularization of tissue-engineered bone grafts promotes repair of femoral bone defects in rats
Donglin LI ; Pengzhen CHENG ; Huijie JIANG ; Jimeng WANG ; Yi GAO ; Shuaishuai ZHANG ; Tianqing CAO ; Junqin LI ; Chunmei WANG ; Liu YANG ; Guoxian PEI
Chinese Journal of Orthopaedic Trauma 2017;19(4):333-339
Objective To investigate the effect of prevascularized tissue-engineered bone graft on regeneration of femoral bone defects in rats.Methods Models of femoral bone defect were created at the bilateral hind limbs of 20 healthy female 10 week-old rats which were divided into 2 even groups randomly (n =10).In group A,conventional tissue-engineered bone grafts were transplanted into the femoral bone defects;in group B,tissue-engineered bone grafts and vascular bundles were implanted into the femoral defects.At 1,4 and 8 weeks after operation,3 rats were sacrificed each time in each group to harvest samples.The remaining one in each group served as a spare animal.Regeneration of bone defects and degradation of scaffolds were assessed by radiologic modality and hematein eosin staining.Results At week 1,the new bone ratio (BV/TV) was 5.47% ± 1.90% in group A and 8.49% ± 1.26% in group B,showing no significant difference (P > 0.05);at weeks 4 & 8,the BV/TV were 17.54% ±2.04% and 39.73% ± 4.01% in group A,significantly lower than those in group B (25.32% ± 2.15% and 53.22% ± 2.94%) (P < 0.05).At weeks 1 & 4,the scaffold degradation ratios (RSV/SV) were 97.33% ± 2.52% and 80.60% ±4.00%,showing no significant differences from those in group B (95.67% ±3.51% and 75.22% ±6.20%) (P > 0.05).At week 8,the scaffold degradation ratio in group A (65.46% ±4.51%) was significantly higher than that in group B (50.19% ±4.91%) (P < 0.05).At week 8,hematein eosin staining showed better integration of scaffolds with the femur,faster degradation of the interior scaffolds and greater osteogenetic activity in group B.Conclusion Prevascularization of tissue-engineered bone graft may increase new bone volume and scaffold degradation rate,promoting repair of femoral bone defects in rats.
3.Construction and validation of risk prediction models for unplanned readmissions within 30 days in elderly emergency patients based on different machine learning algorithms
Pengzhen WANG ; Hengya JIA ; Jin LIU
Chinese Journal of Practical Nursing 2024;40(29):2285-2292
Objective:To construct the risk prediction model of unplanned readmission for elderly patients in emergency department within 30 days based on different machine learning algorithms, so as to help clinical staff identify high-risk patients early and formulate preventive interventions.Methods:A total of 1 207 elderly patients admitted to the emergency department of the First Affiliated Hospital of Naval Medical University from May 2022 to December 2023 were retrospectively selected as the study objects and were divided into the training set ( n = 842) and the test set ( n = 365) in a ratio of approximately 7∶3. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen the factors affecting the unplanned readmission of elderly patients within 30 days. Six prediction models, including extreme Gradient Boost (XGBoost), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost) Logistic regression, K-nearest neighbor (KNN) and Gauss Naive Bayes classification (GNB) were constructed respectively. The models were summarized, evaluated and validated, and the importance of key variables was analyzed using Shapley Additive Interpretation (SHAP). Results:Among 1 207 elderly patients, there were 842 in the training set, 430 males with a median age of 77 years, and 365 in the test set, 176 males with a median age of 78 years. Eight variable features were selected by LASSO regression. The GNB model performed the best among the 6 prediction models constructed based on XGBoost, LightGBM, AdaBoost, Logistic regression, KNN, GNB. The AUC of the test set was 0.818, and the sensitivity was 0.890, while the specificity was 0.660, and the train set and the verification set had strong fitting ability and high stability. The eight characteristics affecting the unplanned readmitted of elderly patients in the emergency department within 30 days were ranked in importance by age, chronic obstructive pulmonary disease, length of stay, Charson comorbidity index≥3, hypoproteinemia, abnormal vital signs≥2, stroke, anemia.Conclusions:The GNB model based on machine learning algorithms for unplanned readmission of elderly emergency patients within 30 days has good predictive performance, which helps medical staff to identify high-risk patients as early as possible before discharge, formulate targeted preventive measures, thereby reducing the short-term unplanned readmission rate of patients and improving their quality of life.
4.Intravascular NK/T cell lymphoma: report of 2 cases and review of literature
Longrong RAN ; Pengzhen WANG ; Zailin YANG
Journal of Leukemia & Lymphoma 2023;32(10):605-608
Objective:To investigate the clinical features,differential diagnosis and treatment of intravascular NK/T cell lymphoma.Methods:The clinical data and diagnosis and treatment process of 2 patients with intravascular NK/T cell lymphoma admitted to Chongqing University Cancer Hospital were retrospectively analyzed, and related literatures were reviewed.Results:Both patients were initially presented with cutaneous symptoms. Patient 1 was diagnosed with intravascular NK/T cell lymphoma, and received 4 courses of programmed-death receptor 1 (PD-1) inhibitor toripalimab + P-Gemox (pegaspargase + gemcitabine + oxaliplatin) regimen, 1 course of PD-1 + ME (toripalimab + mitoxantrone + etoposide) regimen and then underwent autologous hematopoietic stem cell transplantation; patient 2 was diagnosed with intravascular NK/T cell lymphoma involving the nasal cavity, and received 4 courses of P-Gemox regimen, and then received autologous hematopoietic stem cell transplantation in the other hospital. Both patients achieved good therapeutic efficacy.Conclusions:Intravascular NK/T cell lymphoma is very rare, frequently involving the skin and central nervous system. Intravascular growth of tumor cells derived from NK cells is the key point of diagnosis and differential diagnosis. P-Gemox regimen and hematopoietic stem cell transplantation could bring better curative effect.
5.Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease.
Qian GUO ; Xiaoyao ZHENG ; Peng YANG ; Xiaoying PANG ; Kang QIAN ; Pengzhen WANG ; Shuting XU ; Dongyu SHENG ; Liuchang WANG ; Jinxu CAO ; Wei LU ; Qizhi ZHANG ; Xinguo JIANG
Acta Pharmaceutica Sinica B 2019;9(3):590-603
Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.