1.Exercise preconditioning combined with bone marrow mesenchymal stem cell transplantation for myocardial infarction in rats
Zhikun WANG ; Shaoxuan BAI ; Wei ZHAO ; Chenyu WANG
Chinese Journal of Tissue Engineering Research 2025;29(1):65-73
BACKGROUND:Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction;however,alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells.Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium.However,little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation. OBJECTIVE:To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment. METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group,and combination group,with 20 rats in each group.The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery.The sham operation group was only threaded without ligature.The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling.In addition,the combination group also required 8 weeks of treadmill exercise(i.e.,exercise preconditioning)before modeling.Four weeks after stem cell transplantation,exercise performance was measured by incremental exercise exhaustion test;cardiac structure and function were measured by echocardiography;left ventricular hemodynamics was measured by pressure-volume catheterization,and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained.Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor(interleukin-1β,interleukin-6,tumor necrosis factor-α),anti-inflammatory factor(interleukin-10),sex-determining region of Y chromosome,and fetal genes(atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain)mRNA expression level at 1,7 days and 4 weeks after stem cell transplantation. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:compared with sham operation group,exercise performance,and left ventricular ejection fraction were reduced(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were increased(P<0.05);the mRNA expression of fetal genes and pro-inflammatory factors were up-regulated(P<0.05),and the mRNA expression of interleukin-10 was down-regulated(P<0.05)in the model group.Compared with the model group,exercise performance and left ventricular ejection fraction were increased(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were decreased(P<0.05);mRNA expression of fetal genes and pro-inflammatory factors was down-regulated(P<0.05),and that of interleukin-10 had no significant change(P>0.05)in the transplantation group.Compared with the transplantation group,all the above indicators in the combination group were further improved(P<0.05).(2)One day and 7 days after stem cell transplantation,compared with the transplantation group,the mRNA expression of sex-determining region of Y chromosome in the combination group increased(P<0.05).(3)Correlation analysis showed that interleukin-1β,interleukin-6(except on the 1st day after transplantation),and tumor necrosis factor-α were negatively correlated with the mRNA expression of sex-determining region of Y chromosome(P<0.05),while interleukin-10 was positively correlated with that of sex-determining region of Y chromosome(P<0.05).These findings suggest that exercise preconditioning can enhance the effect of bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction,which is characterized by suppression of cardiac remodeling and further amelioration of cardiac function.The mechanism is related to the improvement of the myocardial inflammatory microenvironment to promote bone marrow mesenchymal stem cell retention and survival.
2.Establishment and application of an artificial intelligence-assisted platform for detection of parasite eggs
Huiyin ZHU ; Yuting LI ; Daiqian ZHU ; Yaqian WANG ; Jinhong ZHANG ; Shaoxuan CHEN ; Xiaoyuan MA ; Huidi WANG ; Hongjun LI ; Jian LI
Chinese Journal of Schistosomiasis Control 2024;36(6):643-648
Objective To establish an artificial intelligence (AI)-assisted platform for detection of parasite eggs, and to evaluate its detection efficiency and accuracy, so as to provide technical supports for elimination of parasitic diseases. Methods A total of 1 003 slides of Enterobius vermicularis, horkworm, Trichuris trichiura, Clonorchis sinensis, Taenia, Ascaris lumbricoides, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski eggs were collected, and converted into digital images with an automatated scanning microscope to create a dataset. Based on the Object Detection platform on the Baidu Easy DL model, an AI-assisted platform for detection of parasite eggs was created through procedures of uploading, labeling, training, evaluation and optimization. Then, 70% of the datasets were randomly selected for model training, and the precision, recall and average accuracy were calculated to evaluate the effectiveness of platform for recognition of parasite eggs. In addition, the platform was deployed on the computer and smart phone terminals for use. Results An AI-assisted platform for detection of parasite eggs was successfully created. If the platform was deployed using the public cloud application programming interface (API), the average accuracy, precision and recall of the platform were 93.42%, 92.55% and 89.32% for recognition of parasite eggs. If the platform was deployed using the offline software development kit (SDK), the average accuracy, precision and recall of the platform were 92.97%, 94.78% and 87.63% for recognition of parasite eggs. In addition, the precision of the platform was 97.00% and 96.23% for identification of Taenia and C. sinensis eggs, respectively. Conclusions The AI-assisted platform for detection of parasite eggs has been successfully created, which is high in the accuracy for recognition of parasite eggs and convenient in use. This platform may provide a powerful technical support for parasitic disease diagnosis.
3.Effect of teriparatide on residual back pain after percutaneous kyphoplasty for osteoporotic thoracolumbar compression fracture
Yunxuan LI ; Jun SHU ; Zhihua WANG ; Hangchuan BI ; Limin GUO ; Shaoxuan HE ; Nannan KOU ; Hanbo CHEN
Chinese Journal of Trauma 2022;38(3):198-204
Objective:To investigate the effect of teriparatide on residual back pain (RBP) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was used to analyze the clinical data of 90 OVCF patients sustaining RBP after PKP admitted to Second Affiliated Hospital of Kunming Medical University from September 2015 to March 2019, including 18 males and 72 females, at age of 57-85 years[(68.0±5.9) years]. Teriparatide treatment was applied regularly in 32 patients (teriparatide group) and antiosteoporosis drug was administered routinely in 58 patients (routine treatment group). Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between the two groups before operation, at 24 hours, 1 month, 3 months, 6 months and 12 months after operation. Anterior vertebral body height (ABH), middle vertebral body height (MBH), kyphosis angle (KA), maintenance rate of anterior vertebral body height (MRABH), maintenance rate of middle vertebral body height (MRMBH) and difference of kyphosis angle (DKA) were measured at 24 hours and 12 months after operation to evaluate the maintenance of vertebral height and incidence of vertebral refracture. Levels of type I collagen carboxy-terminal peptide (β-CTX) and serum N-terminal osteocalcin (N-MID) were measured before operation and at 12 months after operation to evaluate the improvement of bone metabolism. The adverse reactions of teriparatide group were observed.Results:All patients were followed up for 12-36 months[(14.3±0.6)months]. VAS and ODI were decreased gradually with time in both groups (all P<0.01). There were no significant differences in VAS between the two groups before operation and at 24 hours after operation (all P>0.05). Teriparatide group showed VAS of (4.4±0.6)points, (3.2±0.5)points, (2.0±0.5)points, (1.1±0.1)points at 1, 3, 6 and 12 months after operation, significantly lower than those in routine treatment group[(4.9±0.6)points, (4.0±0.6)points, (3.2±0.7)points, (2.7±0.1)points, respectively](all P<0.01). Teriparatide group showed ODI of 26.5±1.3 and 20.6±1.2 at 6 months and 12 months after operation, significantly lower than those in routine treatment group (28.2±1.6, 23.6±1.6) (all P<0.01). There were no significant differences in ODI between the two groups at other time points (all P>0.05). Both groups presented significantly lowered levels of ABH and MBH at 12 months after operation as compared with those at 24 hours after operation (all P<0.01). There were no significant differences in ABH or MBH between the two groups at 24 hours after operation (all P>0.05). ABH, MBH, MRABH and MRMBH in teriparatide group were (1.9±0.2)cm, (1.7±0.2)cm, 0.91±0.02 and 0.92±0.02 at 12 months after operation, significantly higher than those in routine treatment group[(1.7±0.2)cm, (1.6±0.2)cm, 0.86±0.02 and 0.87±0.02](all P<0.01). KA in both groups showed significant increase at 12 months after operation as compared with that at 24 hours after operation (all P<0.01). There was no significant difference in KA between the two groups at 24 hours after operation ( P>0.05). KA in teriparatide group was (7.3±0.7)° at 12 months after operation, significantly lower than (9.5±0.5)° in routine treatment group ( P<0.01). DKA in teriparatide group was (5.3±1.3)° at 12 months after operation, significantly lower than (6.6±1.4)° in routine treatment group ( P<0.01). Incidence of vertebral refracture in teriparatide group was 7% (2/32), significantly lower than 35% (15/58) in routine treatment group ( P<0.05). Level of β-CTX was not significantly different between and within the two groups before operation and at 12 months after operation (all P>0.05). There was no significant difference in N-MID between the two groups before operation ( P>0.05). After treatment for 12 months, level of N-MID in teriparatide group was significantly increased[19.5 (17.6, 20.9)pg/ml]as compared with that before operation[18.2 (14.6, 21.0)pg/ml]( P<0.01), and was significantly higher than that in routine treatment group[17.6 (15.3, 19.9)pg/ml]( P<0.01). Routine treatment group showed no significant difference in level of N-MID before operation and at 12 months after operation ( P>0.05). Two patients in teriparatide group had orthostatic hypotension after treatment. Conclusion:For OVCF patients with RBP after PKP, teriparatide can effectively alleviate pain, improve motor dysfunction, maintain the height of bone cement vertebral body, reduce incidence of vertebral refracture and enhance the activity of osteoblasts, with less adverse reactions.
5.Risk factors of adjacent segment diseases after lumbar fusion
Yunxuan LI ; Yong LIU ; Jun SHU ; Zhihua WANG ; Shaoxuan HE ; Limin GUO ; Nannan KOU ; Hanbo CHEN ; Jia LYU ; Hao DUAN
Chinese Journal of Orthopaedics 2022;42(19):1283-1291
Objective:To explore the risk factors of adjacent segment diseases (ASDis) after lumbar fusion, summarize the prevention strategies and provide reference for clinical treatment.Methods:All of 258 patients who underwent lumbar interbody fusion from March 2014 to March 2019 were retrospectively analyzed, including 95 males and 163 females, the age of whom was 61.8±8.4 years (range, 39-77 years). The patients were divided into ASDis group and non-ASDis group according to whether ASDis occurred at the follow-up of 24 months after operation. The patient's individual factors [gender, age, body mass index (BMI), main diagnosis, preoperative paraspinal muscle fatty degree, etc.] and surgical factors (operation type, fixed segment, fusion segment, etc.), sagittal parameters [lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL] were recorded. After univariate analysis of potential risk factors, the factors with P<0.05 were substituted into logistic regression model for multivariate analysis to determine the risk factors of ASDis after lumbar fusion. Results:ASDis occurred in 24 patients after lumbar fusion, with an incidence of 9.3% (24/258); univariate analysis showed that age ≥ 60 years old, complicated with osteoporosis, preoperative fatty degree of paraspinal muscle (GCS grade≥3), PLIF operation, suspension fixation, total laminectomy and multi-segment fusion (≥ 3 segments) were the potential risk factors for ASDis after operation (P<0.05); Gender, education level, partner status, type of work, BMI, obesity (BMI≥24 kg/m 2) , smoking, use of bisphosphonates, concomitant lumbar spinal stenosis, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle, sacral slope angle, and PI-LL had no significant correlation with ASDis. Logistic regression analysis showed that age ≥ 60 years ( OR=5.63, 95% CI: 1.56, 20.29, P=0.008), preoperative paravertebral muscle fatty GCS ≥ 3 ( OR=4.82, 95% CI: 1.36, 17.13, P=0.015), combined with osteoporosis ( OR=14.04, 95% CI: 2.53, 77.79, P=0.002), PLIF ( OR=9.69, 95% CI: 1.91, 49.03, P=0.001), and multi-segment fixation ( OR=9.36, 95% CI: 1.77, 49.41, P=0.008) were the risk factors for ASDis after lumbar fusion; Incomplete laminectomy ( OR=0.09, 95% CI: 0.02, 0.37, P=0.001) and suspension fixation ( OR=0.16, 95% CI: 0.02, 0.94, P=0.042) were the protective factors of ASDis after lumbar fusion. Conclusion:The patients with age ≥ 60 years old, osteoporosis and preoperative paraspinal muscle fatty degree ≥ 3 grade GCS should be more careful in choosing the surgical methods, and try to choose transforaminal interbody fusion, posterolateral fusion, short segment fusion, decompression with preservation of vertebral lamina, suspension fixation and other surgical methods to reduce the incidence of postoperative ASDis.
6.A status analysis of the direct intrahepatic portacaval shunt (DIPS) treatment for portal hypertension
Jinmiao WANG ; Xiaoyu LIANG ; Yan CHEN ; Shaoxuan BAI
Chinese Journal of Hepatobiliary Surgery 2019;25(1):74-76
Transjugular intrahepatic portosystemic shunt (TIPS) is a surgery which was commonly used in portal hypertension therapy.It can control and prevent the complication caused by portal hypertension,such as esophageal gastric-fundus variceal bleeding.However,there is a fundamental flaw in the TIPS due to its lack of maintaining a long-lasting and effective shunt,and most of the stenosis or occlusion are in the draining vein:the hepatic vein.Accompanied by direct intrahepatic portosystemic shunt (DIPS),which has shown its advantage compared with traditional TIPS operation,such as the block of hepatic vein can be avoided,the radiation dose as well as the operation time is lesser,DIPS is safer and so on.Here we reviewed to present a brief introduction of DIPS development history and core concerns of the major medical centers at present.
7.Detection and analysis of EBV DNA integration in NK/T cell lymphoma genome
Xin WANG ; Xudong ZHANG ; Qingjiang CHEN ; Guannan WANG ; Junxia HU ; Shaoxuan WU ; Mijing MA ; Meifeng YIN ; Wanqiu YANG ; Meng DONG ; Mengjie DING ; Mingzhi ZHANG ; Linan ZHU
Chinese Journal of Clinical Oncology 2018;45(23):1194-1200
To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.
8.Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoprolif-erative disorders
Junxia HU ; Qingjiang CHEN ; Xudong ZHANG ; Wencai LI ; Guannan WANG ; Xin WANG ; Meng DONG ; Shaoxuan WU ; Mijing MA ; Meifeng YIN ; Wanqiu YANG ; Mengjie DING ; Mingzhi ZHANG ; Linan ZHU
Chinese Journal of Clinical Oncology 2018;45(24):1248-1253
Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.
9.Exploration of dissemation model for advanced medical techniques
Li YAO ; Yunting WANG ; Bogu SU ; Shaoxuan CHEN
Chinese Journal of Medical Science Research Management 2013;(2):94-98
In order to find out appropriate model to best disseminate laparoscopy for colorectal cancer clinical advanced technologies,it is necessary to establish a whole set of training system,which included selecting training site,intensive training,operation observation,advanced study at home and abroad,technical support,etc..Evaluation was based on operation time,hemorrhage in surgery,other injuries in surgery,conversion to open surgery and the ratio of in situ relapse in one year post surgery.These five indexes were compared between the training group and the control group with the gradually stable trend of learning curve as standard.Without previous laparoscopic surgery experience,the training group required 13.8±0.75,14±0.89,10.2±0.74,16.4±0.49 and 20.4±0.49 cases,respectively,to achieve expected proficiency,and the control group required 28.6± 1.69,29.2±1.16,27.8 ± 0.74,22.8 ± 0.40 and 25.4± 1.03 cases,respectively.The learning time required 13.4± 1.02 months on average for the training group and 27.8±2.13 months for the control group.In conclusion,the training system achieved obvious superiority to the controls to achieve expected skills and proficiency in laparoscopy for colorectal cancer.
10.Effects of psychological stress on small intestinal bacteria and mucosa in mice
Chinese Journal of Behavioral Medicine and Brain Science 2008;17(3):210-211
Objective To investigate the effects of psychological stress on small intestinal bacteria and mucosa in mice, and to explore the relationship between small intestinal disfunction and small intestinal bacteria and mucosa under psychological stress. Methods 48 mice were randomly divided into psychological stress group and control group. An animal model with psychological stress was established lodging the mice and a hungry cat in separate layers of a two-layer cage. D-xylose levels in plasma were measured for estimating the damage degree of small intestinal mucosa. A section of the proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (Escherichia coli) and anaerobes (Lactobacilli). The quantitation of bacteria was expressed as log10[colony forming units/g]. Results D-xylose concentrations in plasma in psychological stress mice were significantly higher than those in the control group (3.02±0.85 mmol/L vs 0.94±0.33 mmol/L,P<0.01).Psychological stress resulted in quantitative alterations in the aerobes (E. coli). There was an increase in the number of E. coli in the proximal small intestinal flora (1.79±0.27 log10(CFU/g) vs 1.32±0.22 log10(CFU/g),P<0.01), and there was decrease in relative proportion of Lactobacilli and E. coli of stressed mice (0.52±0.56 vs 1.14±1.07,P<0.05), while there was no significant difference in the anaerobes(Lactobacilli) between the two groups (2.31±0.63 log10(CFU/g) vs 2.41±0.34 log10(CFU/g) P>0.05). D-xylose concentrations in plasma was significantly and positively correlated with the number of E. coli in the proximal small intestinal flora (r=0.6713,P<0.05). Conclusion Small intestinal disfunction under psychological stress may be related to dysbacteriosis and the damage of mucosa.

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