1.Diagnosis of an Outbreak of Canine Distemper in Cynomolgus Monkeys in an Experimental Monkey Farm in 2019
Chenjuan WANG ; Lingyan YANG ; Lipeng WANG ; Xueping SUN ; Jingwen LI ; Lianxiang GUO ; Rong RONG ; Changjun SHI
Laboratory Animal and Comparative Medicine 2025;45(3):360-367
Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.
2.Diagnosis of an Outbreak of Canine Distemper in Cynomolgus Monkeys in an Experimental Monkey Farm in 2019
Chenjuan WANG ; Lingyan YANG ; Lipeng WANG ; Xueping SUN ; Jingwen LI ; Lianxiang GUO ; Rong RONG ; Changjun SHI
Laboratory Animal and Comparative Medicine 2025;45(3):360-367
Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.
3.Establishment and validation of a risk-scoring model for predicting delayed onset of lactogenesis stage Ⅱ in preterm mothers during maternal separation
Fei SUN ; Min LIU ; Shanshan HU ; Huijuan CHEN ; Jie HUA ; Hui YAN ; Lingyan WU
Chinese Journal of Perinatal Medicine 2024;27(7):544-552
Objective:To construct and validate a risk-scoring model for predicting delayed onset of lactogenesis stage Ⅱ (DOL Ⅱ) in mothers separated from their premature infants.Methods:This was a retrospective study. (1) Modeling group: This group enrolled 310 mothers who were separated from their premature infants after delivery at Wuxi Maternal and Child Health Hospital from December 2021 to November 2022. They were further divided into the DOL Ⅱ group (144 cases) and the non-DOL Ⅱgroup (166 cases) according to whether they had DOL Ⅱ or not. Based on the results of multivariate logistic regression analysis, each risk factor was assigned a score, and a risk prediction scoring model was established. (2) Validation group: This group included 130 mothers of premature infants who experienced mother-infant separation after delivery at Wuxi Maternal and Child Health Hospital from December 2022 to March 2023. The area under the receiver operating characteristic (ROC) curve was used to evaluate the discrimination, and the Hosmer-Lemeshow test was used to assess the goodness of fit. The Chi-square test (or Fisher's exact probability test) or Wilcoxon rank sum test were used for inter-group data comparison. Results:This risk prediction scoring model included 10 risk factors [maternal age≥35 years old, hypertensive disorders of pregnancy, anemia, gestational diabetes mellitus, preterm rupture of membrane, start breastfeeding >6 hours, postpartum admission of maternal intensive care unit, cesarean section, score of Edinburgh Postpartum Depression Scale >9.5, postpartum neutrophil-to-lymphocyte ratio ≥4.369, Fatigue Scale-14 ≥7.5, body mass index in the first trimester ≥23.719 kg/m 2, postpartum BMI≥27.661 kg/m 2,and increase of BMI during pregnancy ≥5.393 kg/m 2], with an area under the ROC curve of 0.838 (95% CI: 0.795-0.882, P<0.001), a maximum Yoden index of 0.526, a specificity of 0.825, a sensitivity of 0.701, and an optimal threshold of 4.5. After rounding the score off to the nearest whole number, those with a score≥5 were defined as at high risk of DOL Ⅱ, while those with a score<5 were at low risk. Hosmer-Lemeshow test showed χ2=3.43 and P=0.634. The positive predictive value, the negative predictive value, and the accuracy were 77.7%, 76.1%, and 76.8%, respectively. In the modeling group, 130 out of the 310 cases (41.9%) were predicted to be at high risk by the model with 101 (32.6%) experiencing DOL Ⅱ, while 180 cases (58.1%) were predicted to be at low risk with 43 (13.9%) experiencing DOL Ⅱ. Among the 130 cases in the validation group, 59 (45.4%) were predicted to be at high risk with 39 (30.0%) experiencing DOL Ⅱ, while 71 (54.6%) were predicted to be at low risk with 19 (14.6%) experiencing DOL Ⅱ. The model validation results showed that the area under the ROC curve was 0.774 (95% CI: 0.693-0.855, P<0.001) and the Hosmer-Lemeshow test showed χ2=3.09 and P=0.687, with the positive predictive value of 66.1%, the negative predictive value of 73.2%, and the accuracy of 70.0%. Conclusions:This study preliminarily establishes a risk scoring model for predicting DOL Ⅱ in mothers separated from their premature infants which is of certain predictive value and can provide a reference for developing predictive lactation support measures.
4.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
5.Role of p-AKT-mTOR-P70S6K signaling pathway in radiation therapy for polyploid cervical cancer cells
Li ZHOU ; Ying YAN ; Fanjie MENG ; Song ZHAO ; Shuo LIU ; Lingyan SUN ; Huiying YU
Cancer Research and Clinic 2024;36(8):569-575
Objective:To investigate the role of p-AKT-mTOR-P70S6K signaling pathway in radiation therapy for polyploid cervical cancer cells.Methods:Human cervical cancer HeLa cell lines were selected and HeLa cells were radiated under 7 Gy of 6 MV X-ray. The morphological changes of the cells were observed with an inverted microscope on day 5 after radiation induction. All cells were divided into the 7 Gy group (7 Gy X-ray radiation but not transfected polyploidy HeLa cells) and the control group (the non-radiation-induced and not transfected HeLa cells). In addition, the plasmid carrying pcDNA3 negative control sequence and the plasmid carrying pcDNA3-TT-AKT sequence were transfected into HeLa cells, respectively, which were induced by 7 Gy X-ray radiation after 48 h of transfection, and then they were recorded as the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group. Cell proliferation ability was detected by using CCK-8 assay, cell cycle was detected by using flow cytometry, cell apoptosis was detected by using mitochondrial membrane potential assay, the relative expression levels of cell proliferation, cell cycle, apoptosis and autophagy related proteins were tested by using Western blot.Results:Most of the normal HeLa cells in the 7 Gy group died on day 5 after radiation induction, and only a few surviving cells increased in size with multiple nuclei. The results of Western blot showed that the relative expression levels of p-AKT, p-mTOR and p-P70S6K in HeLa cells of the 7 Gy group were lower than those of the control group (all P < 0.05). CCK-8 assay showed that the absorbance ( A) values were 0.45±0.06, 0.65±0.06 after 48 h of culture and 0.75±0.05, 1.05±0.02 after 72 h of culture, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant (all P < 0.05), and the A values in the pcDNA3-TT-AKT + 7 Gy group were all higher than those in the pcDNA3 +7 Gy group. Flow cytometry results showed that the proportion of cells was (29.2±3.6)%, (26.7±1.7)% in G 0/G 1 phase and (29.6±1.6)%, (30.3±0.6)% in G 2/M phase, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were not statistically significant (all P > 0.05); the proportion of cells in S phase was (10.2±0.9)% and (14.6±1.5)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant ( t = 2.86, P = 0.043). Mitochondrial membrane potential assay showed that the green fluorescence proportion was (23.1±2.5)% and (14.3±1.9)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the different was statistically significant ( t = 4.82, P = 0.009). Western blot results showed that the relative expression level of p-cdc25c (Ser216) in the pcDNA3-TT-AKT+7 Gy group was higher than that in the pcDNA3+7 Gy group ( P < 0.001); and the relative expression levels of Bak and LC3-Ⅱ/Ⅰ in the pcDNA3-TT-AKT+7Gy group were lower than those in the pcDNA3 +7 Gy group, respectively (all P < 0.05). Conclusions:The p-AKT-mTOR-P70S6K signaling pathway may be involved in the regulation of radiation-induced polyploidy HeLa cell proliferation, cell cycle and cell apoptosis.
6.Comparative efficacy of vNOTES and LESS in the management of benign uterine lesions in obese patients
Wenyuan LI ; Min WEI ; Jie HAN ; Ruifeng LI ; Zhen WANG ; Hailan LI ; Jing XU ; Dongmei JIN ; Lingyan XU ; Rong PENG ; Yan ZHANG ; Xinhua SUN
The Journal of Practical Medicine 2024;40(22):3184-3189
Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.
7.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
8.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
9.Effects of sarcopenia on the occurrence of overt hepatic encephalopathy in patients with liver cirrhosis
Lingyan CAI ; Chunyan SUN ; Xin ZENG
Chinese Journal of Digestion 2023;43(6):376-381
Objective:To investigate the risk factors of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis, and to clarify the effect of sarcopenia on OHE.Methods:Based on the liver cirrhosis cohort established by our research group, from January 1, 2013 to December 31, 2017, 480 patients diagnosed with liver cirrhosis and underwent upper abdominal computed tomography were selected from 3 centers, including the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai East Hospital Affiliated to Tongji University, and Shandong Provincial Hospital. The L3 skeletal muscle index (L3-SMI) <44.77 cm 2/m 2 for males and L3-SMI <32.50 cm 2/m 2 for females were used as the diagnostic criterion for sarcopenia. The clinical data of all the patients were collected, including baseline medical history, age, serum total bilirubin, serum levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), albumin, sodium, prothrombin time (PT), international normalized ratio (INR), hemoglobin, platelet count, etc, as well as Child-Pugh classification of liver function, and model for end-stage liver disease (MELD) score. Independent sample t test, rank sum test, and chi-square test were used for statistical analysis. Binary logistic regression analysis was used to analyze the independent risk factors for OHE in patients with liver cirrhosis, and Kaplan-Meier method was used to analyze the effect of sarcopenia on the incidence of OHE in patients with liver cirrhosis. Results:After 2 years of follow-up, the incidence of OHE was 16.2% (78/480). The age, serum total bilirubin level, AST, GGT, PT, INR, Child-Pugh score, and MELD score of OHE patients were all higher than those of non-OHE patients ((59.67±10.30) years old vs. (53.41±12.06) years old, 35.25 μmol/L(20.10 μmol/L, 60.53 μmol/L) vs. 22.70 μmol/L(15.10 μmol/L, 35.20 μmol/L), 40.00 U/L(27.25 U/L, 61.00 U/L) vs. 33.00 U/L(24.75 U/L, 47.00 U/L), 52.50 U/L(26.25 U/L, 86.75 U/L) vs. 34.50 U/L(22.00 U/L, 73.00 U/L), (17.71±3.52) s vs. (15.50±2.98) s, 1.50±0.34 vs. 1.31±0.29, 8.95±2.19 vs.7.20±1.94, 13.56±4.42 vs.11.42±3.92), while serum albumin, serum sodium and platelet count of OHE patients were all lower than those of non-OHE patients ((29.72±5.55) g/L vs. (33.19±5.89) g/L, 139.00 mmol/L(136.00 mmol/L, 142.00 mmol/L)vs.140.00 mmol/L (138.00 mmol/L, 142.00 mmol/L), 60.00×10 9/L(43.75×10 9/L, 90.25×10 9/L) vs. 80.00×10 9/L(56.00×10 9/L, 131.00×10 9/L)), and the differences were statistically significant ( t=-4.77; Z=-4.10, -3.13, -2.24; t=-5.19, -4.71, -6.57, -3.98, 4.99; and Z=2.44 and 3.48; all P<0.05). The proportions of ascites, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis at baseline, and the incidence of sarcopenia in OHE patients were all higher than those in non-OHE patients (82.1%, 64/78 vs. 63.7%, 256/402; 41.0%, 32/78 vs. 3.5%, 14/402; 5.1%, 4/78 vs. 1.0%, 4/402; 14.1%, 11/78 vs. 2.5%, 10/402; 37.2%, 29/78 vs. 19.7%, 79/402), and the L3-SMI of OHE patients was lower than that of non-OHE patients ((43.14±8.97) cm 2/m 2 vs. (46.29±8.49) cm 2/m 2), and the differences were statistically significant ( χ2=9.11, 101.97, 4.52, 18.38, 10.53; t=2.86; all P<0.05). The results of binary logistic regression analysis indicated that platelet count ( OR=0.995, 95% confidence interval (95% CI) 0.991 to 1.000, P=0.038), L3-SMI ( OR=0.959, 95% CI 0.922 to 0.997, P=0.035) and hepatic encephalopathy ( OR=14.724, 95% CI 6.741 to 32.161, P<0.001) were independent influencing factors for OHE in patients with liver cirrhosis. The incidence of OHE in patients with sarcopenia was higher than that of patients without sarcopenia (26.9%, 29/108 vs. 13.2%, 49/372), and the difference was statistically significant ( χ2=10.53, P=0.001). The results of Kaplan-Meier analysis demonstrated that patients with sarcopenia were more likely to develop OHE ( P<0.001). Conclusion:Sarcopenia is closely correlated to OHE and is an independent predictor of OHE in patients with liver cirrhosis.
10.Study on changes of proliferation, migration and invasion abilities of radiation-induced polyploid colon cancer SW1116 cells and their progeny and the related mechanisms
Li ZHOU ; Ying YAN ; Fanjie MENG ; Song ZHAO ; Shuo LIU ; Lingyan SUN ; Huiying YU
Cancer Research and Clinic 2023;35(3):161-166
Objective:To investigate the characteristics related to proliferation, migration and invasion of radiation-induced polyploid colon cancer SW1116 cells and their progeny.Methods:Colon cancer SW1116 cells were conventionally cultured in Leibovitz's L-15 medium containing 10% fetal bovine serum. SW1116 cells at logarithmic growth stage were irradiated with 7 Gy X-ray, and the morphological changes of the cells were observed by inverted microscope on days 3, 5, 10 and 19 after radiation induction. According to the morphological changes of the cells, the cells at day 3 after radiation induction were labeled as polyploid giant cancer cell (PGCC) group, and the cells at day 19 were recorded as PGCC progeny group. SW1116 cells without radiation induction were used as control group. Flow cytometry was used to detect cell ploidy in the control, PGCC and PGCC progeny groups, CCK-8 assay was used to detect the proliferation ability of the three groups, cell migration and invasion abilities of the three groups were detected by cell scratch assay and Transwell assay, and Western blotting was used to detect the expressions of cell cycle and proliferation-related proteins and epithelial-mesenchymal transition (EMT) marker N-cadherin (N-cad) in the three groups.Results:The volume of SW1116 cells gradually became larger on days 3, 5 and 10 after radiation induction, and returned to normal on day 19. The proportions of polyploid (DNA content >4N) cell subsets in the control group, PGCC group and PGCC progeny group were (2.3±1.1)%, (23.1±8.1)% and (3.2±0.5)%, the difference was statistically significant ( F = 18.52, P < 0.05), and the proportion of polyploid cell subpopulations in the PGCC group was higher than that in the control group ( t = 5.38, P < 0.01), but the differences between the PGCC progeny group and the control group were not statistically significant ( t = 0.22, P > 0.05). After 72 h of culture, the cell proliferation rates of the control, PGCC and PGCC progeny groups were (100.0±4.1)%, (73.5±0.7)% and (123.9±3.5)%, and the difference was statistically significant ( F = 190.27, P < 0.001). After 48 h of cell scratching, the scratch healing rates in the control, PGCC and PGCC progeny groups were (38.0±2.7)%, (41.5±4.0)% and (63.7±4.2)%, and the difference was statistically significant ( F = 43.05, P < 0.001). After 24 h of culture, the number of invasive cells in the control, PGCC and PGCC progeny groups was 12.9±1.2, 3.4±0.6 and 23.7±1.5, and the difference was statistically significant ( F = 63.64, P < 0.001). The expression levels of cell cycle-related proteins P-cdc25c, cdc25c and cdc2 in the PGCC group were lower than those in the control group (all P < 0.05), and the expression levels of transcription factor-related proteins E2F-2, E2F-3 and EMT marker N-cad were downregulated compared with the control group (all P < 0.05); the expression levels of P-cdc25c, cdc25c, cdc2, E2F-2, E2F-3 and N-cad proteins in the PGCC progeny group were higher than those in the control group (all P < 0.05). Conclusions:Radiation can induce colon cancer SW1116 cells to produce polyploid, which may then generate daughter cells through asymmetric mitosis and gain new life, and then promote the recurrence and metastasis of colon cancer.

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