1.Mechanism of Lijin manipulation regulating scar formation in skeletal muscle injury repair in rabbits
Kaiying LI ; Xiaoge WEI ; Fei SONG ; Nan YANG ; Zhenning ZHAO ; Yan WANG ; Jing MU ; Huisheng MA
Chinese Journal of Tissue Engineering Research 2025;29(8):1600-1608
BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.
2.Application and challenge of immunotherapy in perioperative therapy of gastric cancer
Chi XUE ; Peng GAO ; Zhi ZHU ; Zhenning WANG
China Oncology 2024;34(3):259-267
Gastric cancer is one of the common malignant tumors of digestive system in our country.The proportion of patients in advanced and late stage is large,and the choice of perioperative treatment program is always difficult in clinic.For most locally advanced gastric cancer,compared with standard radical surgery combined with postoperative adjuvant chemotherapy,perioperative treatment mode may further improve the survival of patients.However,the efficacy of conventional chemotherapy regimen has reached a plateau,while the progress of traditional molecular targeted therapy is relatively slow.In recent years,with the increasing role of immunotherapy in the treatment of advanced gastric cancer,more and more clinical studies have shown that immunotherapy can also achieve better efficacy in perioperative gastric cancer patients.This article reviewed the research progress of immunotherapy in perioperative gastric cancer in recent years.
3.Diagnostic value of cervical cell DNA ploidy analysis combined with B7-H4 and PKCδ for cervical cancer
Ningning ZHANG ; Zhe YANG ; Limei TAN ; Zhenning LI ; Di WANG ; Yongzhi WEI
Journal of International Oncology 2024;51(5):286-291
Objective:To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 (B7-H4) and protein kinase Cδ (PKCδ) for cervical cancer.Methods:A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime, 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results, they were divided into normal or inflammatory group ( n=52), low-grade cervical intraepithelial neoplasia (CIN) group ( n=68) and high-grade CIN group ( n=40). The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic (ROC) curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results:The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were 16 (30.8%), 27 (39.7%), 26 (65.0%) and 127 (79.4%), respectively, with a statistically significant difference ( H=55.86, P<0.001). Further pin-by-pair comparison showed that compared with normal or inflammatory groups, the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher (both P<0.05). The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group ( P<0.05). Serum B7-H4 levels in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were (57.21±10.21), (79.17±11.34), (92.73±15.36), (126.56±20.25) ng/ml, respectively, with a statistically significant difference ( F=285.45, P<0.001). Serum PKCδ levels were (89.34±18.29), (71.79±15.82), (53.39±11.84), (40.23±10.21) ng/ml, respectively, with a statistically significant difference ( F=216.28, P<0.001). Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups, low-grade CIN group, high-grade CIN group and cervical cancer group increased in turn (all P<0.05). Serum PKCδ levels in normal or inflammatory groups, high-grade CIN group and cervical cancer group were decreased in turn (all P<0.05). Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated ( r=-0.47, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 (95% CI: 0.78-0.86), and the sensitivity and specificity were 83.9% and 79.9%, respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 95.7% and 76.1%, respectively, and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 85.6% and 88.9%, respectively, and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 (95% CI: 0.97-0.99), and the sensitivity and specificity were 98.3% and 75.9%, respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy ( Z=8.00, P<0.001), serum B7-H4 ( Z=4.34, P<0.001), and serum PKCδ ( Z=4.61, P<0.001) alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum ( OR=2.94, 95% CI: 1.78-4.84, P<0.001), low level of PKCδ ( OR=4.33, 95% CI: 1.88-10.00, P=0.001) and positive DNA ploidy in cervical cells ( OR=5.77, 95% CI: 2.38-13.99, P<0.001) were independent risk factors for cervical cancer. Conclusion:The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased, the serum B7-H4 level is increased, the PKCδ level is decreased, and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.
4.Effects of computerized cognitive remediation therapy combined with social skill training on the negative symptoms of schizophrenia
Xianli FAN ; Zhenning WU ; Kewen WU ; Yutao ZHANG ; Lijuan BAI ; Yan WANG ; Dongmei YAN ; Xiu WU ; Huifang BAI ; Zhirui LI
Chinese Journal of Primary Medicine and Pharmacy 2023;30(2):235-239
Objective:To investigate the effects of computerized cognitive remediation therapy (CCRT) combined with social skill training on the improvement of negative symptoms of schizophrenia.Methods:A total of 102 schizophrenic patients who received treatment in Shanxi Province Social Welfare Kangning Psychiatry Hospital from March 2019 to June 2021 were included in this study. They were randomly divided into an intervention group and a control group ( n = 51/group). During the intervention process, because of the reasons such as midway discharge, only 93 patients were included in the final analysis, consisting of 47 patients in the intervention group and 46 patients in the control group. All patients received social skills training. Patients in the intervention group received 8-week CCRT. The Positive and Negative Syndrome Scale and Social Skills Checklist were used to evaluate curative effect in the two groups. Results:After treatment, total score of the Positive and Negative Syndrome Scale and the score of negative symptoms in the intervention group were (46.36 ± 9.33) points and (11.15 ± 3.53) points, respectively, which were significantly lower than (51.06 ± 10.26) points and (16.42 ± 4.75) points in the control group ( t = 2.07, 5.41, both P < 0.05). The total score of Social Skills Checklist, conflict resolution ability score and relationship building ability score in the intervention group were (16.05 ± 6.85) points, (3.36 ± 1.65) points and (3.14 ± 1.83) points, respectively, which were significantly lower than (21.08 ± 8.24) points, (5.92 ± 2.35) points and (6.75 ± 2.51) points, respectively ( t = 2.87, 5.34, 7.00, all P < 0.01). Conclusion:CCRT combined with social skill training can effectively improve the negative symptoms of patients with schizophrenia.
5.Research hotspots and frontier trends of flame retardants-induced adverse health effects on humans: A visualized bibliometric analysis
Danlei YANG ; Zhenning ZHANG ; Cheng-chen WANG ; Daolei CUI ; Zhihua DENG ; Ping XIANG
Journal of Environmental and Occupational Medicine 2022;39(4):410-418
Background As emerging environmental contaminants with ecological risks, flame retardants (FRs) exhibit obvious toxicity and persistence. In recent years, as FRs have been widely detected in indoor environments and human samples, the human health risks after FRs exposure are of great concern. Objective To systematically understand the topic evolution, research status, progress, and development trends on the toxicity and health effects of FRs on humans worldwide. Methods We retrieved the literature regarding toxicity of FRs and their effects on human health through the Web of Science database from 2000 to 2020, screened and processed the literature using Endnote software, and analyzed annual publications, important citations, and authors. CiteSpace and VOSviewer were employed to draw co-citation network, keyword co-occurrence network, and keyword clustering map for bibliometric visualization analysis. Results From 2000 to 2020, 472 international papers on toxic effects and human health impacts of FRs were published. In terms of publication years, FRs-related research was mainly divided into three stages: the infancy and exploration stage (2001—2006), when the research on the toxic effects of FRs was just starting; the growth stage (2007—2015), when the risk assessments of FRs on human health were conducted; and the acceleration stage (2016—), when the studies have shifted to the mechanism of FRs damage to human health. In this field, China published the largest number of published articles in the world (177 papers), but the intermediary centrality (reflecting academic influence) was only 0.19, far lower than that of European and American countries such as the Netherlands (0.78), Britain (0.51), and Germany (0.44). Among the top 10 research institutions in terms of the number of articles published, the Chinese Academy of Sciences topped the list with 49 articles. Van der Veen and other researchers had a strong influence on the research of the toxic effects of phosphorous FRs since their papers published in 2012 were cited 1319 times and in the most prominent node in the literature co-citation network. The high-frequency keywords in the literature on the human health effects of FRs were polybrominated diphenyl ethers (217 times), brominated FRs (166 times), toxicity (147 times), FRs (102 times), exposure, polychlorinated biphenyls, in vitro experiment, plasticizer, etc. Through keyword clustering and co-occurrence analyses, it was found that current research is systematically exploring the toxic mechanism of FRs from a perspective integrating pollution source-exposure route-final receptor of pollutants, and is evaluating the environmental health risks via different exposure routes. The visualized bibliometric analysis findings suggested that future studies understand the underlying mechanisms of various cell damage caused by FRs toxicity, identify the key factors of change and their relationships, aiming to provide a scientific basis for targeted prevention of health effects of FRs. Conclusion The research hotspots on the toxic effects of FRs and their effects on human health have changed over time, and the breadth and depth have been increasing. The toxic effects of brominated/phosphorus FRs have always been the mainstream direction in this field. Further studies will focus on the molecular mechanisms of human toxicity after FRs exposure.
6.Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis
Song YONGXI ; Wang JUN ; Sun JINGXU ; Chen XIAOWAN ; Shi JINXIN ; Wu ZHONGHUA ; Yu DEHAO ; Zhang FEI ; Wang ZHENNING
Genomics, Proteomics & Bioinformatics 2020;18(6):679-695
Gastric cancer (GC) is known as a top malignant type of tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated pro-teins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. More-over, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating character-istic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) values of this model were 0.996 and 0.886 for the training and testing sets, respectively, suggesting that the four-protein signature has a high diag-nostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC value of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC.
7.Research progress of translational medicine for gastric cancer
Zhenning WANG ; Zhi ZHU ; Jingxu SUN
Chinese Journal of Digestive Surgery 2018;17(4):338-342
Gastric cancer is one of the most common malignant digestive tumors globally.The comprehensive treatment based on surgery of gastric cancer can not satisfy the purpose to reduce morbidity and mortality.In recent years,translational medicine has emerged with the rapid development of basic medical research,such as molecular biology,and the change of medical patterns.The core of translational medicine is to establish a fast conversion channel between basic research and clinical applications which could translate basic research results into theories,technologies and products for clinical practice.In the present paper,the research progress of translational medicine in the diagnosis and treatment of gastric cancer will be summarized,and the role of translational medicine for precise treatment of gastric cancer will be discussed.
8.Effect of ERH gene knockdown on the proliferation and apoptosis of T24 cells in human bladder cancer
Kun PANG ; Lin HAO ; Zhenduo SHI ; Bo CHEN ; Zhiguo ZHANG ; Rongsheng ZHOU ; Guanghui ZANG ; Fei ZHOU ; Zijian SONG ; Tian XIA ; Xitao WANG ; Zhenning WEI ; Conghui HAN
Cancer Research and Clinic 2018;30(11):729-734
Objective To investigate the effect of ERH gene knockdown on the proliferation and apoptosis of human bladder cancer T24 cells. Methods T24 cells infected by lentivirus with interference on ERH gene sequence were cloned to establish stable T24 cells clone in ERH gene suppression. The expression of ERH mRNA gene in bladder cancer was detected by using quantitative real time polymerase chain reaction (qPCR). The effects of ERH knockout on the cell proliferation and apoptosis were examined by using methylthiazolyl tetrazolium (MTT) assay, colony formation assay and flow cytometry. The effect of ERH knockout on the tumorigenic effect of T24 cells in vivo was verified by subcutaneous tumor formation in nude mice. Results After lentiviral transfection, qPCR results showed that the knockdown effect of ERH mRNA in ERH normal group (untreated T24 cells) was better than that in ERH gene knockdown group, and the difference was statistically significant [(1.006±0.126) vs. (0.079±0.007); t=12.72, P=0.0002]. After knocking out ERH gene, MTT assay showed that the proliferation ability of T24 cells in ERH gene knockdown group was weakened compared with ERH normal group, and the difference was statistically significant [A490 value: (0.13±0.00) vs. (0.66±0.01);t=104.61, P<0.0001]. Colony formation assay indicated that the ability of clone in ERH normal group was weakened compared with ERH gene knockdown group [(10.5 ±1.2) vs. (196.4 ±4.0); t= 73.63, P< 0.0001]. Flow cytometry showed that the cell apoptosis rate in ERH gene knockdown group was higher than that in ERH normal group [(11.0 ±0.5) % vs. (4.2 ±0.5) %; t= 16.06, P<0.0001]. Imaging results of subcutaneous tumor formation in nude mice showed that the total fluorescence intensity of the tumor area in ERH gene knockdown group was (4.67 ±0.59) × 1010 μW/cm2, and the corresponding part in ERH normal group was (9.54±4.20) × 1010μW/cm2 (t=3.64, P=0.0051);tumor weight in ERH gene knockdown group was (0.80±0.62) g, and in ERH normal group was (1.79±0.71) g (t=3.33, P=0.0037). Conclusion ERH gene knockout can inhibit the proliferation of human bladder cancer T24 cells, and promote the cell apoptosis.
9.Effect of taurine on kidney injury induced by paraquat poisoning in rats
Haitao SHEN ; Na WU ; Yu WANG ; Zhiguang CHEN ; Zhenning LIU ; Min ZHAO
Chinese Journal of Pathophysiology 2017;33(7):1295-1300
AIM: To study the effects of taurine at different doses on renal oxidative stress and inflammation induced by paraquat in rats.METHODS: Male SD rats (n=48) were randomly divided into 4 groups: negative control group, paraquat group, paraquat + low-dose taurine group, and paraquat + high-dose taurine group.The serum levels of creatinine and urea nitrogen were detected by a biochemical analyzer.The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by colorimetry.The plasma concentrations of IL-6 and intercellular adhesion molecule (ICAM)-1 were detected by ELISA.Renal reactive oxygen species (ROS) was checked by fluorescence probe dihydroethidium (DHE).The protein levels of renal p-P38 MAPK, p-ERK1/2 and p-JNK were determined by Western blot.The mRNA expression of TNF-α, IL-6 and TGF-β1 was detected by real-time PCR.RESULTS: Serum creatinine and urea nitrogen increased after paraquat poisoning, and decreased after feeding with taurine in poisoned rats, with better result in high-dose taurine group.Taurine reduced the oxidative stress and inflammation in the renal tissue, and also reduced the protein levels of p-JNK, p-ERK1/2 and p-P38 in the kidney of paraquat-poisoned rats.CONCLUSION: Taurine attenuates renal injury induced by paraquat poisoning in rats.The mechanism may be related to reducing renal MAPK activity, oxidative stress and inflammatory response.
10.Integration and analysis of associated data in surgical treatment of gastric cancer based on multicenter, high volume databases.
Wei WANG ; Zhe SUN ; Jingyu DENG ; Zhenning WANG ; Zhiwei ZHOU ; Han LIANG ; Huimian XU
Chinese Journal of Gastrointestinal Surgery 2016;19(2):179-185
OBJECTIVETo elucidate the current diagnosis and treatment status of gastric cancer in the Chinese population based on three high volume databases.
METHODSClinical and pathological data of patients who underwent gastric cancer resection with complete follow-up information between January 2000 and December 2012 from Sun Yat-sen University Cancer Center, The First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital were retrospectively analyzed. The overall survival rate was calculated by Kaplan-Meier method. The prognostic risk factors were analyzed by using Cox proportional hazards model.
RESULTSA total of 8 338 cases were enrolled into the study, including 2 977 cases (35.7%) from Sun Yat-sen University Cancer Center, 3 043 cases (36.5%) from The First Affiliated Hospital of China Medical University and 2 318 cases (27.8%) from Tianjin Medical University Cancer Hospital. There were 5 852 male cases and 2 486 female cases with a ratio of 2.4 to 1.0. The age of patients was from 15 to 89 years old (median 59 years old). The ratio of early gastric cancer (T1NanyM0) was 11.5% (956/8 338). There were 2 226 gastric cancer cases (26.7%) originating from the fundus and cardiac region, 1 637 cases (19.6%) from the body, 3739 (44.9%) cases from the antrum, and 736 cases (8.8%) from the whole stomach. The median maximal tumor diameter was (4.5 ± 2.8) cm. Based on the Lauren classification, 3 448 cases (41.4%) were intestinal type and 4 890 cases (58.6%) diffuse type. A total of 1 975 cases (23.7%) and 6 363 cases (76.3%) underwent complete and subtotal gastrectomy respectively. The majority of patients (7 707 cases, 92.4%) underwent radical gastric resection, while 631 cases (7.6%) palliative resection. According to AJCC/UICC seventh edition of gastric cancer TNM staging system, 802 patients (9.6%) were stage I(A, 735 patients (8.8%) stage I(B, 695 patients (8.3%) stage II(A, 1 507 patients (18.1%) stage II(B, 1 247 patients (15.0%) stage III(A, 1 342 patients (16.1%) stage III(B, 1 583 patients (19.0%) stage III (C and 427 patients (5.1%) stage IIII(. The average number of retrieved lymph node was 21.0 ± 13.1, in which 5 761 patients (69.1%) had more than 15 retrieved lymph nodes. The overall 1-, 3-, 5- and 10-year survival rates were 83.0%, 56.8%, 49.1% and 43.0% respectively. For patients receiving radical resection, the 1-, 3-, 5- and 10-year survival rates were 84.9%, 59.5%, 51.7% and 45.3% respectively. The overall 5-year survival rates for different stages were as follows: stage I(A 93.8%, stage I(B 80.8%, stage II(A 70.8%, stage II(B 59.6%, stage III(A 44.4%, stage III(B 32.9%, stage III(C 18.9% and stage IIII( 10.2%. Cox regression model showed that age, tumor site, tumor size, Lauren type, T staging, N staging, M staging and number of retrieved lymph nodes were independent factors affecting the prognosis of gastric cancer patients (P=0.000).
CONCLUSIONRetrospective study on these domestic three high volume databases demonstrates the clinical and pathological characteristics of gastric cancer based on Chinese population, which is expected to stand as a ground of basic data for future clinical research.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Databases, Factual ; Female ; Gastrectomy ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; diagnosis ; surgery ; Survival Rate ; Young Adult

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