1.Effects of micro-electric field on proliferation and osteogenic differentiation of human umbilical cord mesenchymal stem cells
Zhong LIU ; Kewei LI ; Min WANG ; Wenhui LIU ; Leilei ZHANG ; Song GUO ; Hui QIAN ; Qiang FU
Chinese Journal of Tissue Engineering Research 2024;28(13):1983-1988
BACKGROUND:Electrical stimulation is a physical method that can be used to induce various cellular activities such as cell proliferation,differentiation,and apoptosis.The induction of osteogenic differentiation of stem cells will be beneficial in the field of bone regeneration. OBJECTIVE:To observe whether micro-current field can promote the proliferation and osteogenic differentiation of human umbilical cord mesenchymal stem cells. METHODS:The fresh human umbilical cord tissue was cut to obtain umbilical cord mesenchymal stem cells,which were inoculated into a 6-well plate after cell culture and passage to the third generation.After 24 hours,the cells were cultured under a stimulation of 0,50,and 100 mV/mm micro-electric field,at a frequency of 1 hour per day for 3 continuous days.The growth and morphological changes of human umbilical cord mesenchymal stem cells were observed by a microscope.The cell proliferation was detected by CCK-8 assay and EdU staining.Alizarin red staining was used to detect the osteogenic differentiation ability of cells.Western blot assay was used to determine the expression of ERK signal pathway proteins. RESULTS AND CONCLUSION:(1)The optical density value and the number of proliferating cells in 50 and 100 mV/mm groups were significantly higher than those of the unstimulated group(P<0.05).(2)Human umbilical cord mesenchymal stem cells could be induced to differentiate into osteocytes before and after micro-electric field stimulation,but the differentiation rate of 50 and 100 mV/mm groups was faster than that of unstimulated groups.(3)The protein expression of p-ERK1/2 in the 50 and 100 mV/mm groups was higher than that in the unstimulated group,and significant difference was detected between the 100 mV/mm group and the unstimulated group(P<0.05).(4)Micro-electric field can promote the proliferation of human umbilical cord mesenchymal stem cells,and the mechanism may be achieved by promoting the phosphorylation of ERK.
2.Genetic characterization of varicella-zoster virus in Jilin province from 2010 to 2023
Xiang LI ; Leilei WEI ; Biao HUANG ; Tao CHENG ; Yuanchun SHAN ; Guixiang QIN ; Hongyan SUN ; Shangwei JI ; Xin TIAN ; Simei FU ; Shuang WANG
Chinese Journal of Experimental and Clinical Virology 2024;38(5):521-526
Objective:This study aimed to analyze the genomic characteristics of Varicella-Zoster Virus (VZV) strains circulating in Jilin province from 2010 to 2023.Methods:Vesicle fluid from 78 sporadic cases with VZV infection were collected in Jilin province from 2010 to 2023, after detecting by Real-time PCR, 26 specimens (CT<25) were detected by PCR. Open reading frame 22(ORF22), ORF38 and ORF62 were amplified and analyzed. Genotyping was confirmed by SNPs ORF22 (37902, 38019, 38055, 38081 and 38177) and ORF38 (69424). Vaccine strains were indentified from wild-type strains according to ORF38 (69349) and ORF62 (106262, 107252, and 108111). Sequences were analyzed by homologous comparison and phylogenetic analysis.Results:The comparison with Dumas sequence revealed that SNPs (37902, 38055, 38081 and 38177) in ORF22 and ORF38 (69424) have mutations similar to the pOka strain, which belong to clade 2. Compared to the Dumas and Baike strains, all 26 samples were wild-type strains. JL2016-4 strain changes from threonine to asparaginyl at position 38059, JL2021-4 strain changes from arginine to proline at position 37933, from aspartic acid to tyrosine at position 37935, and from aspartic acid at base 38031 to tyrosine. JL2023-1 strain changes from arginine to leucine at position 37933.Conclusions:VZV has been prevalent for 14 years in Jilin province. The main epidemic strains belong to the clade 2. We should strengthen the monitoring of VZV outbreaks and raise the coverage rate of VZV vaccination.
3.Application of virtual surgery combined with three-dimensional guide plate in the surgery of mandibular benign tumors resection and bone defect repairation
Kun FU ; Ning GAO ; Leilei YANG ; Kangyan LIU ; Jinghua CAI ; Zhenjie GAO ; Hao CHEN ; Bin ZHAO ; Wei HE
Chinese Journal of Plastic Surgery 2024;40(3):258-263
Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.
4.Application of virtual surgery combined with three-dimensional guide plate in the surgery of mandibular benign tumors resection and bone defect repairation
Kun FU ; Ning GAO ; Leilei YANG ; Kangyan LIU ; Jinghua CAI ; Zhenjie GAO ; Hao CHEN ; Bin ZHAO ; Wei HE
Chinese Journal of Plastic Surgery 2024;40(3):258-263
Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.
5.Logistic regression model study of thromboelastogram parameters on cognitive impairment in patients with recurrent ischemic stroke
Leilei FU ; Weiwei CHEN ; Liuyan WANG
Chinese Journal of Postgraduates of Medicine 2024;47(10):949-953
Objective:To evaluate the diagnostic value of thromboelastogram (TEG) parameters for cognitive impairment in patients with recurrent ischemic stroke (RIS), and construct a nomograph model.Methods:The clinical data of 75 patients with RIS and treated in the Yiwu Central Hospital from June 2020 to June 2022 were retrospectively summarized. Multivariate Logistic regression model was used to screen the risk factors of cognitive impairment in RIS patients. R software was used to establish a nomogram model, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of TEG index and nomogram on cognitive impairment in RIS patients.Results:The results of multivariate Logistic regression analysis showed that National Institutes of Health Stroke Scale (NIHSS) score on admission, stroke interval, change in clotting time 48 h after admission and 48 h before discharge (ΔR) and change in maximum clot intensity (ΔMA) were the risk factors for cognitive impairment 3 months after RIS ( P<0.05). Age, ΔR and ΔMA were the risk factors for cognitive impairment 12 months after the onset of RIS ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) predicted by the nomogram for cognitive impairment 3 and 12 months after the onset of RIS was higher than that of the patients with ΔR and ΔMA ( P<0.01). Conclusions:Detection of TEG parameters, especially ΔR and ΔMA, establishment of nomogram model have good practical value for guiding clinical rapid identification of high-risk patients with cognitive impairment.
6.Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.
Leilei FU ; Wenke JIN ; Jiahui ZHANG ; Lingjuan ZHU ; Jia LU ; Yongqi ZHEN ; Lan ZHANG ; Liang OUYANG ; Bo LIU ; Haiyang YU
Acta Pharmaceutica Sinica B 2022;12(2):532-557
Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.
7.Assessment of platelet function using a Platelet Function Analyzer-100 for metabolic syndrome patients
Tingting WANG ; Li FU ; Yinfeng ZHANG ; Lingling LIU ; Lili MA ; Leilei DING ; Li LI
Chinese Journal of Health Management 2021;15(2):163-166
Objective:Metabolic syndrome (MS) patients and determine factors related to platelet hyperactivation.Methods:A total of 999 participants (822 males and 177 females) were enrolled. Participants were divided into two groups according to the metabolic index: MS group (501) and normal control (NC) group (498). Platelet function was tested with PFA100 (Siemens USA, Deerfield, Illinois) which measures the time it takes for blood to occlude an aperture (closure time, CT) following stimulation with collagen and adenosine diphosphate. Statistical analyses were performed using the SPSS statistical software package, version 22.0 (IBM Corporation, Armonk, NY, USA).Results:MS group had significantly shorter CT values compared with NC group (106.6±27.8s) vs (113.7±27.9s). Higher BMI, WC, BP, TC, TG, LDL-C, UA, and PRL were correlated with shorter CT values (all P<0.05). Conclusion:Our results indicated platelet hyperactivation exists in MS which was related to obesity and elevated blood pressure, blood lipids, uric acid, and PLR.
8.Predicting response to non-small cell lung cancer immunotherapy using pre-treatment contrast-enhanced CT texture-based classification
Leilei SHEN ; Guangyu TAO ; Hongchao FU ; Xuemei LIU ; Xiaodan YE ; Jianding YE
Chinese Journal of Oncology 2021;43(5):541-545
Objective:To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy.Methods:From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results:In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95% CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion:Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.
9.Predicting response to non-small cell lung cancer immunotherapy using pre-treatment contrast-enhanced CT texture-based classification
Leilei SHEN ; Guangyu TAO ; Hongchao FU ; Xuemei LIU ; Xiaodan YE ; Jianding YE
Chinese Journal of Oncology 2021;43(5):541-545
Objective:To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy.Methods:From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results:In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95% CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion:Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.
10.Effect of massive blood transfusion protocol on curative effect and coagulation function of patients with multiple injuries
Chinese Journal of Primary Medicine and Pharmacy 2020;27(11):1335-1339
Objective:To explore and analyze the effect of massive transfusion protocol (MTP) in early massive transfusion and prevention of coagulation disease for patients with multiple injuries.Methods:A retrospective analysis was made in 117 patients with multiple injuries admitted to Yiwu Central Hospital from March 2015 to May 2019.According to different blood transfusion schemes, they were divided into control group(53 cases) and observation group(64 cases). The patients in the control group received routine blood transfusion scheme, and the patients in the observation group received MTP blood transfusion scheme.The changes of blood routine and coagulation function, the amount of blood loss within 24h, the amount of allogeneic blood component input, the length of hospital stay and mortality were compared between the two groups.Results:The levels of Hb, HCT and PLT in the two groups after 24h of blood transfusion were significantly higher than admission[(112.73±12.73)g/L vs.(96.74±10.28)g/L, (115.28±19.27)g/L vs.(95.37±11.47)g/L, (39.72±5.21)% vs.(31.47±4.22)%, (39.10±4.97)% vs.(30.56±4.13)%, (220.93±54.28)×10 9/L vs.(142.83±36.47)×10 9/L, (216.87±64.03)×10 9/L vs.(148.96±40.22)×10 9/L, t=7.818, 6.464, 9.844, 9.621, 9.554, 6.538, all P<0.05], but there were no statistically significant differences between the two groups( t=0.681, 1.172, 0.864, 0.746, 0.740, 1.363, all P>0.05). After 24h of blood transfusion, the time of Pt and APTT in the observation group were significantly lower than admission[(13.21±2.93)s vs.(16.28±4.26)s, (46.28±3.97)s vs.(54.37±6.42)s, t=4.705, 8.574, all P<0.05], but there were no statistically significant changes in the control group[(15.84±3.62)s vs.(16.93±5.17)s, (54.02±6.39)s vs.(55.29±7.02)s, t=0.212, 0.332, all P>0.05]. The time of Pt and APTT in the observation group after 24h of blood transfusion were significantly lower than those in the control group ( t=4.344, 8.006, all P<0.05). There were no statistically significant differences in FIB levels between the two groups[(4.30±0.48)g/L vs.(4.36±0.56)g/L, (4.41±0.58)g/L vs.(4.51±0.63)g/L, t=0.651, 0.934, all P>0.05]. There were no statistically significant differences in 24h bleeding volume and fresh frozen plasma(RBC) input between the two groups[(2 684.92±703.47)mL vs.(2 725.86±810.32)mL, (17.28±3.74)U vs.(17.02±2.95)U, t=0.293, 0.411, all P>0.05]. The input amount of red blood cell suspension(PF) and the ratio of PF: RBC in the observation group were significantly higher than those in the control group[(9.28±3.27)U vs.(6.29±3.18)U, (0.55±0.12) vs.(0.39±0.10), t=4.985, 7.733, all P<0.05]. The observation group had significantly lower SOFA scores and ICU stays compared with the control group[(5.93±1.64)points vs.(7.28±2.10)points, (7.21±1.85)d vs.(9.10±2.37)d, t=3.814, 4.732, all P<0.05], and the mortality rate in the observation group was significantly lower than that in the control group[6.25%(4/64) vs.20.75%(11/53), χ 2=5.457, P<0.05]. Conclusion:The standardized rescue strategy of a large number of blood transfusion treatment schemes and the early proportion of components of blood products (erythrocyte suspension, fresh frozen plasma, platelets) can significantly improve the coagulation function of patients with multiple injuries, reduce the incidence of coagulopathy and help reduce the fatality rate of major bleeding, which is worthy of clinical promotion.

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