1.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.
2.Predictive value of early indicators changes in blood test on the prognosis of patients with acute paraquat poisoning
Linlin CHAO ; Zhenning LIU ; Min ZHAO ; Mengying YANG ; Yongzhuang YE ; Guigui WEI
Chinese Critical Care Medicine 2020;32(6):732-736
Objective:To investigate the predictive value of early indicators changes in blood test on the prognosis of patients with acute paraquat poisoning.Methods:The clinical data of patients with acute paraquat poisoning admitted to emergency department of Shengjing Hospital of China Medical University from January 2012 to June 2019 were retrospectively analyzed. The changes of blood test indexes within 24 hours after admission were collected, including white blood cell count (ΔWBC), neutrophils count (ΔNE), lymphocytes count (ΔLY), monocytes count (ΔMO), arterial partial pressure of oxygen (ΔPaO 2), arterial partial pressure of carbon dioxide (ΔPaCO 2), arterial blood pH (ΔpH), bicarbonate radical (ΔHCO 3-), base excess (ΔBE), lactate (ΔLac), total protein (ΔTP), albumin (ΔALB), alanine aminotransferase (ΔALT), aspartate aminotransferase (ΔAST), total bilirubin (ΔTBil), direct bilirubin (ΔDBil), blood urea nitrogen (ΔBUN), serum creatinine (ΔSCr), serum calcium concentration (ΔCa 2+), and serum potassium concentration (ΔK +). Multivariate Logistic regression was used to analyze the risk factors of prognosis in patients with acute paraquat poisoning, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of ROC curve for the death of patients with paraquat poisoning. Results:A total of 251 patients with acute paraquat poisoning were included, with 99 cases dead, and the mortality was 39.4%. The increase of the markers including ΔWBC, ΔLac, ΔALT, ΔAST, ΔTBil, ΔDBil, ΔBUN, ΔSCr and ΔK + within 24 hours of admission in the death group were significantly higher than that in the survival group; the decrease of the markers including ΔPaCO 2, ΔHCO 3-, ΔBE, ΔTP, and ΔALB in the death group were significantly greater than those in the survival group. The variables with statistical significance in the above single factor analysis were included in the multivariate Logistic regression analysis. The results showed that ΔLac, ΔSCr and ΔK + were independent risk factors for the prognosis of patients with acute paraquat poisoning [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.662 (0.997-2.772), 1.045 (1.010-1.083) and 4.555 (1.190-17.429), respectively, all P < 0.05]. The area under the ROC curve (AUC) of ΔLac, ΔSCr and ΔK + for predicting death of patients with acute paraquat poisoning was 0.639 (95% CI was 0.505-0773), 0.811 (95% CI was 0.704-0.917), and 0.649 (95% CI was 0.519-0.779), respectively. When the cut-off of ΔLac was 1.85 mmol/L, the sensitivity was 87.9%, the specificity was 47.7%, and the diagnostic accuracy was 70.2%; when the cut-off of ΔSCr was 37.75 μmol/L, the sensitivity was 84.4%, the specificity was 77.9%, and the diagnostic accuracy was 80.5%; when the cut-off of ΔK + was 0.42 mmol/L, the sensitivity was 36.6%, the specificity was 90.7%, and the diagnostic accuracy was 68.3%. The efficiency of combination of ΔLac, ΔSCr, and ΔK + was greater than a single indicator in predicting death of patients with acute paraquat poisoning, with AUC of 0.911, and 95% CI of 0.834-0.989. Conclusions:ΔLac, ΔSCr, ΔK + within 24 hours of admission were all independent risk factors for the prognosis of patients with acute paraquat poisoning. ΔSCr > 37.75 μmol/L within 24 hours of admission would predict a poor prognosis in the patients with acute paraquat poisoning. Combined analysis of ΔLac, ΔSCr, and ΔK + can predict the prognosis of paraquat poisoning patients more accurately than single index.
3.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.
4.Experimental study of the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment
Zhenduo SHI ; Zhenning WEI ; Lin HAO ; Kun PANG ; Jiahe ZHOU ; Bingzheng DONG ; Zhiguo ZHANG ; Yan ZHAO ; Yufeng SUN ; Conghui HAN
Chinese Journal of Radiological Medicine and Protection 2020;40(8):573-581
Objective:To investigate the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment. Methods:125I-RSOAds-hTERT/PSA ( 125I-virus complex) oncolytic adenovirus was constructed by PCR amplification and double restriction enzyme ligation. TUNEL staining, flow cytometry and Caspase-3 immunoblotting assay were used to detect the killing effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on prostate cancer cells in vitro and in vivo, respectively. To explore the effect of 125I-virus complex on tumor tissue cytokine secretion levels, interleukin 2 (IL-2), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the culture supernatant of human prostate cancer cell line PC3, mouse prostate adenocarcinoma cell line RM-1, and mice serum were detected by ELISA. We explored the regulation of 125I-virus complex on the expression of CD24, CD44 and prostate stem cell antigen (PSCA) in prostate tumor tissues and tumor cells through immunohistochemistry. Meanwhile, the expression levels of CD32 and vascular endothelial growth factor (VEGF), as well as CD4+ , CD8+ and macrophage infiltration in tumor tissue were detected through immunofluorescence experiments. Results:125I-virus complex oncolytic adenovirus significantly increased tumor cell apoptosis in vitro and in vivo that was significantly higher than that of 125I group and virus complex group. Meanwhile, IL-2 ( t=-183.30, -38.20, P<0.05), IL-10 ( t=113.80, 92.71, P<0.05), TNF-α ( t=-73.20, -73.91, P<0.05), IFN-γ ( t=-65.37, -139.70, P<0.05) increased in vitro and in vivo. 125I-virus complex reduced the expression of CD24, CD44 and PSCA in tumor cells and tumor tissue, reduced the weight of tumor tissue, inhibited angiogenesis of tumor tissue ( t=8.55, P<0.05), and regulated the immune response in tumor tissue. Conclusions:125I-virus complex targeting prostate cancer can significantly kill cancer cells, reduce the weight and angiogenesis of tumor, and improve tumor microenvironment.
5.Video-assisted thoracoscopic lung resection in tuberculosis treatment: A retrospective cohort study
DING Chao ; LIU Yugang ; WEI Lin ; GU Zhenning ; ZHU Changsheng
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2019;26(7):653-659
Objective To investigate the feasibility of video-assisted thoracoscopic surgery (VATS) lung resection in the treatment of tuberculosis. Methods We retrospectively analyzed the clinical data of 164 tuberculosis patients who underwent lung resection in Xi'an Chest Hospital from 2013 to 2017. Patients were divided into two groups according to the surgical procedure: a VATS group (85 patients, 56 males and 29 females) and a thoracotomy group (79 patients, 52 males and 27 females). The clinical effect of the two groups was compared. Results Compared to the thoracotomy group, the VATS group had less operation time (151.59±76.75 min vs. 233.48±93.89 min, P<0.001), amount of intraoperative blood loss (200.00 ml vs. 600.00 ml, P<0.001), the postoperative drainage (575.00 ml vs. 1 110.00 ml, P=0.001), extubation time (4 d vs. 6 d, P<0.001) and hospital stay (13.00 d vs. 17.00 d, P<0.001). There was no statistical difference in postoperative complications (10 patients vs.17 patients, P=0.092) between the two groups. A total of 97 patients underwent lobectomy, including 36 of the VATS group and 61 of the thoracotomy group. The operation time (211.39±70.88 min vs. 258.20±87.16 min, P=0.008), the intraoperative blood loss (400.00 ml vs. 700 ml, P<0.010), the postoperative drainage (800.00 ml vs. 1 250.00 ml, P=0.001), extubation time (5.00 d vs. 8.00 d, P=0.002) and hospital stay (13.11±4.45 d vs. 19.46±7.74 d, P<0.010) in the VATS group were significantly better than those in the thoracotomy group. There was no statistical difference in postoperative complication rate (4 patients vs. 14 patients, P=0.147) between the two[1],groups. Conclusion Compared with conventional thoracotomy, VATS lung resection has obvious advantages in treatment of tuberculosis, which may be the preferred technique.
6.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.
7.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