1.Role of HK2 and VDAC1 in Diacetylmorphine-induced Cardiomyocyte Apoptosis
Jinling XIAO ; Yaling GUAN ; Sensen ZHU ; Mengjie ZHUANG ; Liping SU ; Hongwei PU
Journal of Kunming Medical University 2024;45(2):7-13
Objective To investigate the role of HK2 and VDAC1 in diacetylmorphine-induced cardiomyocyte apoptosis.Methods A dose-escalation method was used to establish a rat model of diacetylmorphine addiction.Forty SD rats were randomly divided into three groups,the normal group(n=10)was injected with an equal amount of saline subcutaneously,the model group(n=15)was injected with 5 mg/kg of diacetylmorphine for the first time,and then the dose was increased by 2.5 mg/(kg·d)day by day for 20 days,and the group of model +10 D(n=15)continued to increase the dose based on the model group up to the 10th day.Lactate dehydrogenase(LDH)and glutamic oxaloacetic transaminase(GOT)were detected by ELISA;HE staining was used to observe the pathological changes of myocardial tissues in each group;TUNEL staining was used to detect apoptosis in myocardial tissues in each group;and immunohistochemistry,RT-q-analysis,and immunochemistry were used to detect apoptosis in myocardial tissues in each group.Immunohistochemistry,RT-qPCR and Western bl-ot were used to detect the mRNA and protein expression of HK2,VDAC1 and apoptosis-related factors.Results HE staining revealed that myocardial tissues exhibited different degrees of damage with the prolongation of diacetylmorphine intervention.Compared with the normal group,serum LDH,GOT content and myocardial apoptosis rate increased in the model group,mRNA and protein levels of HK2 and anti-apoptotic factor Bcl-2 decreased,mRNA and protein levels of VDAC1 and pro-apoptotic factors Bax and Caspase-3 increased,and the protein level of Clevead Caspase-3 increased;in the model +10 D group the above indexes,there was a statistically significant difference(P<0.05).Conclusion Diacetylmorphine can cause cardiomyocyte apoptosis,and VDAC1 may be involved in the process of cardiomyocyte apoptosis caused by diacetylmorphine.
2.Clinical application of narrow elastic disposable tourniquet in liposuction reduction for lower limb lymphedema
Yuan GAO ; Xiaorong QU ; Hongwei ZHENG ; Wenbing SHEN ; Kun HAO ; Lei GUAN
Journal of Jilin University(Medicine Edition) 2024;50(3):791-796
Objective:To analyze the application effect of narrow elastic disposable tourniquet in liposuction reduction surgery for the lower extremity lymphedema,and to provide the basis for its clinical application.Methods:The retrospective analysis was conducted on the clinical data of 309 patients who underwent liposuction reduction surgery for the lower extremity lymphedema.The patients were divided into non-narrow elastic disposable tourniquet group(n=163)and narrow elastic disposable tourniquet group(n=146).The intraoperative blood loss,rates of allogenic blood transfusion,incidence of adverse reactions related to dilation fluid into blood,incidence of blood pressure fluctuations,and preoperative and postoperative 24 h levels of hemoglobin(Hb)and albumin(Alb)of the patients in two groups were compared.Results:Compared with non-narrow elastic disposable tourniquet group,the intraoperative blood loss,allogenic blood transfusion rate,and incidence of adverse reactions related to dilation fluid into blood of the patients in narrow elastic disposable tourniquet group were decreased(P<0.05),while the incidence of intraoperative blood pressure fluctuations was increased(P<0.05).Compared with non-narrow elastic disposable tourniquet group,the ΔHb level(preoperative Hb level-postoperative 24 h Hb level)and ΔAlb level(preoperative Alb level-postoperative 24 h Alb level)of the patients in narrow elastic disposable tourniquet group were decreased(P<0.05 or P<0.01).Conclusion:The application of narrow elastic disposable tourniquet in liposuction reduction surgery for the lower extremity lymphedema can effectively reduce the intraoperative bleeding and the need for allogenic transfusions,decrease the level of ΔAlb,and prevent the occurrence of adverse reactions related to dilation fluid into blood.However,attention should be given to the potential adverse reactions related to intraoperative circulatory fluctuations.
3.Influence of ultrasound guidance combined with CT verification on the puncture effect of radiofre-quency thermocoagulation of semilunar ganglion
Ran WANG ; Xianzhong GAO ; Min HUA ; Weiping LU ; Hua GUAN ; Hongwei SHI ; Chenjie XU
The Journal of Clinical Anesthesiology 2024;40(11):1178-1183
Objective To investigate the puncture effect of radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale with ultrasound guidance and CT verification in the treatment of V3 branch trigeminal neuralgia(TN).Methods Forty-eight V3 branch TN patients,19 males and 29 females,aged>18 years,BMI≤28 kg/m2,undergoing radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale were selected.Patients were divided into two groups by random number table method:ultrasound guidance combined with CT verification group(group U)and CT guidance group(group C),24 patients in each groups.According to grouping result,patients received radiofrequency ther-mocoagulation of semilunar ganglion with foramen ovale puncture performed under the ultrasound guidance and CT verification or CT guidance respectively.The success cases of puncture,the number of puncture,ra-diation dose,puncture time,operation time and the occurrence of treatment complications were recorded.Numerical rating scale(NRS)scores and Barrow neurological institute(BNI)scores were recorded before surgery,2,4,12,and 24 weeks after surgery,and good postoperative pain relief rate(BNI Ⅰ or Ⅱ)was calculated.Results All patients in both groups completed puncture operationand radiofrequency thermo-coagulation.Compared with group C,group U had fewer number of puncture,lower radiation exposure,and shorter puncture and surgical times(P<0.05).Compared with baseline before operation,NRS scores were significantly lower in both groups at 2,4,12,and 24 weeks after surgery(P<0.05).There was no signif-icant difference in the rate of good pain relief 2,4,12,and 24 weeks after surgery between the two groups.There was no significant difference in the incidence of facial hematoma between the two groups.No other se-rious complications were found in both groups.Conclusion Radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale with ultrasound guidance and CT verification is a safe and feasible method for the treatment of the V3 branch TN.Compared with CT guidance,ultrasound guidance combined with CT verification can significantly improve the puncture accuracy and reduce the radiation exposure related to treatment.
4.Investigation and factor analysis of postoperative surgical site infections in emergency abdominal surgery in China from 2018 to 2021 based on Chinese SSI Surveillance
Zhiqiang ZHENG ; Yangyang LIU ; Wenqiang LUO ; Hongwei ZHANG ; Yuyi WANG ; Hong WANG ; Xuemin LI ; Hongping CHEN ; You LI ; Weidong JIN ; He HUANG ; Yuting GUAN ; Hongmei ZHANG ; Shikuan LI ; Jian'an REN ; Peige WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(9):827-836
Objective:We investigated the incidence of surgical site infection (SSI) following emergency abdominal surgery (EAS) in China and further explored its risk factors, providing a reference for preventing and controlling SSI after EAS.Methods:This was an observational study. Data of patients who had undergone EAS and been enrolled in the Chinese SSI Surveillance Program during 2018–2021were retrospectively analyzed. All included patients had been followed up for 30 days after surgery. The analyzed data consisted of relevant patient characteristics and perioperative clinical data, including preoperative hemoglobin, albumin, and blood glucose concentrations, American Society of Anesthesiologists (ASA) score, grade of surgical incision, intestinal preparation, skin preparation, location of surgical site, approach, and duration. The primary outcome was the incidence of SSI occurring within 30 days following EAS. SSI was defined as both superficial and deep incisional infections and organ/space infections, diagnoses being supported by results of microbiological culture of secretions and pus. Secondary outcomes included 30-day postoperative mortality rates, length of stay in the intensive care unit (ICU), duration of postoperative hospitalization, and associated costs. The patients were classified into two groups, SSI and non-SSI, based on whether an infection had been diagnosed. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with SSI following EAS.Results:The study cohort comprised 5491 patients who had undergone EAS, comprising 3169 male and 2322 female patients. SSIs were diagnosed in 168 (3.1%) patients after EAS (SSI group); thus, the non-SSI group consisted of 5323 patients. The SSIs comprised superficial incision infections in 69 (41.1%), deep incision infections in 51 (30.4%), and organ or space infections in 48 (28.6%). Cultures of secretions and pus were positive in 115 (68.5%) cases. The most frequently detected organism was Escherichia coli (47/115; 40.9%). There were no significant differences in sex or body mass index between the SSI and non-SSI groups (both P>0.05). However, the proportion of individuals aged 60 years or older was significantly greater in the SSI than in the non-SSI group (49.4% [83/168] vs. 27.5% [1464/5323), χ 2=38.604, P<0.001). Compared with the non-SSI group, the SSI group had greater proportions of patients with diabetes (11.9% [20/168] vs. 4.8% [258/5323], χ 2=16.878, P<0.001), hypertension (25.6% [43/168] vs. 12.2% [649/5323], χ 2=26.562, P<0.001); hemoglobin <110 g/L (27.4% [46/168] vs. 13.1% [697/5323], χ 2=28.411, P<0.001), and albuminemia <30 g/L (24.4% [41/168] vs. 5.9% [316/5323], χ 2=91.352, P<0.001), and a reduced rate of preoperative skin preparation (66.7% [112/168] vs. 75.9% [4039/5323], χ 2=7.491, P=0.006). Furthermore, fewer patients in the SSI group had preoperative ASA scores of between one and two (56.0% [94/168] vs. 88.7% [4724/5323], χ 2=162.869, P<0.001) in the non-SSI group. The incidences of contaminated and infected incisions were greater in the SSI group (63.1% [106/168] vs. 38.6% [2056/5323], χ 2=40.854, P<0.001). There was a significant difference in surgical site distribution between the SSI and non-SSI groups (small intestine 29.8% [50/168] vs. 10.6% [565/5323], colorectal 26.2% [44/168] vs. 5.6% [298/5 323], and appendix 24.4% [41/168] vs. 65.1% [3465/5323]) χ 2=167.897, P<0.001), respectively. There was a significantly lower proportion of laparoscope or robotic surgery in the non-SSI group (24.4 % [41/168] vs. 74.2% [3949/5323], χ 2=203.199, P<0.001); the percentage of operations of duration less than 2 hours was significantly lower in the SSI than non-SSI group (35.7% [60/168] vs. 77.4% [4119/5323], χ 2=155.487, P<0.001). As to clinical outcomes, there was a higher 30-day postoperative mortality rate (3.0%[5/168] vs. 0.2%[10/5323], χ 2=36.807, P<0.001) and higher postoperative ICU occupancy rate (41.7% [70/168] vs. 19.7% [1046/5323], χ 2=48.748, P<0.001) in the SSI group. The median length of stay in the ICU (0[2] vs. 0[0] days, U=328597.000, P<0.001), median total length of stay after surgery (16[13] vs. 6[5] days, U=128146.000, P<0.001), and median hospitalization cost (ten thousand yuan, 4.7[4.4] vs. 1.7[1.8], U=175965.000, P<0.001) were all significantly greater in the SSI group. Multivariate logistic regression analysis revealed that the absence of skin preparation before surgery (OR=2.435,95%CI: 1.690–3.508, P<0.001), preoperative albuminemia <30 g/L (OR=1.680, 95%CI: 1.081–2.610, P=0.021), contaminated or infected incisions (OR=3.031, 95%CI: 2.151–4.271, P<0.001), and laparotomy (OR=3.436, 95% CI: 2.123–5.564, P<0.001) were independent risk factors of SSI. Operative duration less than 2 hours (OR=0.465, 95%CI: 0.312–0.695, P<0.001) and ASA score of 1–2 (OR=0.416, 95% CI: 0.289–0.601, P<0.001) were identified as independent protective factors for SSI. Conclusions:It is important to consider the nutritional status in the perioperative period of patients undergoing EAS. Preoperative skin preparation should be conducted and, whenever possible, laparoscope or robot-assisted surgery. Duration of surgery should be as short as possible while maintaining surgery quality and improving patient care.
5.Investigation and factor analysis of postoperative surgical site infections in emergency abdominal surgery in China from 2018 to 2021 based on Chinese SSI Surveillance
Zhiqiang ZHENG ; Yangyang LIU ; Wenqiang LUO ; Hongwei ZHANG ; Yuyi WANG ; Hong WANG ; Xuemin LI ; Hongping CHEN ; You LI ; Weidong JIN ; He HUANG ; Yuting GUAN ; Hongmei ZHANG ; Shikuan LI ; Jian'an REN ; Peige WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(9):827-836
Objective:We investigated the incidence of surgical site infection (SSI) following emergency abdominal surgery (EAS) in China and further explored its risk factors, providing a reference for preventing and controlling SSI after EAS.Methods:This was an observational study. Data of patients who had undergone EAS and been enrolled in the Chinese SSI Surveillance Program during 2018–2021were retrospectively analyzed. All included patients had been followed up for 30 days after surgery. The analyzed data consisted of relevant patient characteristics and perioperative clinical data, including preoperative hemoglobin, albumin, and blood glucose concentrations, American Society of Anesthesiologists (ASA) score, grade of surgical incision, intestinal preparation, skin preparation, location of surgical site, approach, and duration. The primary outcome was the incidence of SSI occurring within 30 days following EAS. SSI was defined as both superficial and deep incisional infections and organ/space infections, diagnoses being supported by results of microbiological culture of secretions and pus. Secondary outcomes included 30-day postoperative mortality rates, length of stay in the intensive care unit (ICU), duration of postoperative hospitalization, and associated costs. The patients were classified into two groups, SSI and non-SSI, based on whether an infection had been diagnosed. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with SSI following EAS.Results:The study cohort comprised 5491 patients who had undergone EAS, comprising 3169 male and 2322 female patients. SSIs were diagnosed in 168 (3.1%) patients after EAS (SSI group); thus, the non-SSI group consisted of 5323 patients. The SSIs comprised superficial incision infections in 69 (41.1%), deep incision infections in 51 (30.4%), and organ or space infections in 48 (28.6%). Cultures of secretions and pus were positive in 115 (68.5%) cases. The most frequently detected organism was Escherichia coli (47/115; 40.9%). There were no significant differences in sex or body mass index between the SSI and non-SSI groups (both P>0.05). However, the proportion of individuals aged 60 years or older was significantly greater in the SSI than in the non-SSI group (49.4% [83/168] vs. 27.5% [1464/5323), χ 2=38.604, P<0.001). Compared with the non-SSI group, the SSI group had greater proportions of patients with diabetes (11.9% [20/168] vs. 4.8% [258/5323], χ 2=16.878, P<0.001), hypertension (25.6% [43/168] vs. 12.2% [649/5323], χ 2=26.562, P<0.001); hemoglobin <110 g/L (27.4% [46/168] vs. 13.1% [697/5323], χ 2=28.411, P<0.001), and albuminemia <30 g/L (24.4% [41/168] vs. 5.9% [316/5323], χ 2=91.352, P<0.001), and a reduced rate of preoperative skin preparation (66.7% [112/168] vs. 75.9% [4039/5323], χ 2=7.491, P=0.006). Furthermore, fewer patients in the SSI group had preoperative ASA scores of between one and two (56.0% [94/168] vs. 88.7% [4724/5323], χ 2=162.869, P<0.001) in the non-SSI group. The incidences of contaminated and infected incisions were greater in the SSI group (63.1% [106/168] vs. 38.6% [2056/5323], χ 2=40.854, P<0.001). There was a significant difference in surgical site distribution between the SSI and non-SSI groups (small intestine 29.8% [50/168] vs. 10.6% [565/5323], colorectal 26.2% [44/168] vs. 5.6% [298/5 323], and appendix 24.4% [41/168] vs. 65.1% [3465/5323]) χ 2=167.897, P<0.001), respectively. There was a significantly lower proportion of laparoscope or robotic surgery in the non-SSI group (24.4 % [41/168] vs. 74.2% [3949/5323], χ 2=203.199, P<0.001); the percentage of operations of duration less than 2 hours was significantly lower in the SSI than non-SSI group (35.7% [60/168] vs. 77.4% [4119/5323], χ 2=155.487, P<0.001). As to clinical outcomes, there was a higher 30-day postoperative mortality rate (3.0%[5/168] vs. 0.2%[10/5323], χ 2=36.807, P<0.001) and higher postoperative ICU occupancy rate (41.7% [70/168] vs. 19.7% [1046/5323], χ 2=48.748, P<0.001) in the SSI group. The median length of stay in the ICU (0[2] vs. 0[0] days, U=328597.000, P<0.001), median total length of stay after surgery (16[13] vs. 6[5] days, U=128146.000, P<0.001), and median hospitalization cost (ten thousand yuan, 4.7[4.4] vs. 1.7[1.8], U=175965.000, P<0.001) were all significantly greater in the SSI group. Multivariate logistic regression analysis revealed that the absence of skin preparation before surgery (OR=2.435,95%CI: 1.690–3.508, P<0.001), preoperative albuminemia <30 g/L (OR=1.680, 95%CI: 1.081–2.610, P=0.021), contaminated or infected incisions (OR=3.031, 95%CI: 2.151–4.271, P<0.001), and laparotomy (OR=3.436, 95% CI: 2.123–5.564, P<0.001) were independent risk factors of SSI. Operative duration less than 2 hours (OR=0.465, 95%CI: 0.312–0.695, P<0.001) and ASA score of 1–2 (OR=0.416, 95% CI: 0.289–0.601, P<0.001) were identified as independent protective factors for SSI. Conclusions:It is important to consider the nutritional status in the perioperative period of patients undergoing EAS. Preoperative skin preparation should be conducted and, whenever possible, laparoscope or robot-assisted surgery. Duration of surgery should be as short as possible while maintaining surgery quality and improving patient care.
6.Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer
Ce JU ; Jingchun GAO ; Pengxin ZHANG ; Kaina ZHANG ; Sen YANG ; Tiejin KANG ; Hongzhen ZHAO ; Wenjing QI ; Qiuping ZHANG ; Fandou KONG ; Hongwei GUAN ; Hong SHI
Chinese Journal of Obstetrics and Gynecology 2020;55(8):529-534
Objective:To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis.Methods:The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ,included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed.Results:(1) PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups ( P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different ( P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups ( P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC (type Ⅱ) than those of low-grade (type Ⅰ) and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences ( P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant ( P<0.05). Conclusions:The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.
7.The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification.
Jun GUAN ; Liying XIE ; Xuezhen LUO ; Bingyi YANG ; Hongwei ZHANG ; Qin ZHU ; Xiaojun CHEN
Journal of Gynecologic Oncology 2019;30(1):e13-
OBJECTIVES: Although patients with grade I and II endometrioid endometrial adenocarcinoma (EEA) are considered with good prognosis, among them 15%–25% died in 5 years. It is still unknown whether integrating estrogen receptor (ER) and progesterone receptor (PR) into clinical risk stratification can help select high-risk patients with grade I–II EEA. This study was to investigate the prognostic value of ER and PR double negativity (ER/PR loss) in grade I–II EEA, and the association between ER/PR loss and The Cancer Genome Atlas (TCGA) classification. METHODS: ER and PR were assessed by immunohistochemistry on hysterectomy specimens of 903 patients with grade I–II EEA. ER and PR negativity were determined when < 1% tumor nuclei were stained. Gene expression data were obtained from the TCGA research network. RESULTS: Compared with ER or PR positive patients (n=868), patients with ER/PR loss (n=35) had deeper myometrial infiltration (p=0.012), severer FIGO stage (p=0.004), and higher rate of pelvic lymph node metastasis (p=0.020). In univariate analysis, ER/PR loss correlated with a shorter progression-free survival (PFS; hazard ratio [HR]=5.25; 95% confidence interval [CI]=2.21–12.52) and overall survival (OS; HR=7.59; 95% CI=2.55–22.60). In multivariate analysis, ER/PR loss independently predicted poor PFS (HR=3.77; 95% CI=1.60–10.14) and OS (HR=5.56; 95% CI=1.37–22.55) for all patients, and poor PFS for patients in stage IA (n=695; HR=5.54; 95% CI=1.28–23.89) and stage II–IV (n=129; HR=5.77; 95% CI=1.57–21.27). No association was found between ER/PR loss and TCGA classification. CONCLUSION: Integrating ER/PR evaluation into clinical risk stratification may improve prognosis for grade I–II EEA patients.
Adenocarcinoma*
;
Carcinoma, Endometrioid
;
Classification
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Disease-Free Survival
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Endometrial Neoplasms
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Estrogens*
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Female
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Gene Expression
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Genome
;
Humans
;
Hysterectomy
;
Immunohistochemistry
;
Lymph Nodes
;
Multivariate Analysis
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Neoplasm Metastasis
;
Progesterone*
;
Prognosis
;
Receptors, Progesterone*
8.Expression and significance of MAPK/ERK in the specimens and cells of epithelial ovarian cancer
Xuelian JIANG ; Jingchun GAO ; Li JIANG ; Pengxin ZHANG ; Tiejin KANG ; Qian SUN ; Wenjing QI ; Qiuping ZHANG ; Hongwei GUAN ; Hong SHI
Chinese Journal of Obstetrics and Gynecology 2019;54(8):541-547
Objective To detect phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) protein expression in epithelial ovarian cancer and cell lines,and to examine the effects of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor AZD6244 on cell proliferation,apoptosis as well as cell cycle of ovarian cancer cells.To explore the function and significance of MAPK/extracellular signal-regulated kinase (ERK) signaling pathway in the development of ovarian cancer.Methods (1) A total of 104 cases of patients with ovarian cancer who accepted the treatment of gynecological surgery and being confirmed by pathological examination in First Affiliated Hospital,Dalian Medical University from January 2004 to December 2013 were selected.The expressions of p-ERK1/2 protein were detected by immunohistochemistry in ovarian cancer specimens,and the relationship between the expressions of p-ERK1/2 and the clinical features of patients was analyzed.(2) p-ERK1/2 and other related proteins were determined by western blot in various ovarian cancer cells,including SKOV3,OV2008,C13,A2780S,A2780CP,OVCAR4,OVCAR5,OVCAR8 and CAOV3 treated with or without MEK inhibitor.The cellular proliferation,apoptosis and cell cycle of ovarian cancer cells after treatment with MEK inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry,respectively.Results (1) The immunohistochemical method showed that p-ERK1/2 between low grade serous carcinoma and clear cell carcinoma were not significantly higher expressed (P>0.05).However,a lower level of the p-ERK1/2 expression were observed among high grade serous carcinoma,mucinous carcinoma and endometrioid carcinoma (all P<0.05).There was no significant correlation between the protein expression of p-ERK1/2 and patients' age,pathological stage of surgery,and preoperative serum CA125 level (P>0.05).(2) Western blot showed that the protein p-ERK1/2 was widely expressed in various ovarian cancer cell lines such as SKOV3,OV2008,C13,A2780S,A2780CP,OVCAR4,OVCAR5,OVCAR8 and CAOV3.After treatment with AZD6244 (5,10 μmol/L),the level of p-ERK 1/2 in OVCAR5 and OVCAR8 decreased significantly in dose-dependent manner.Additionally,we found a reduction of the expression level of cyclin D 1,caspase-3 and appeared cleaved poly adenosine diphosphate ribose polymerase (PARP) in OVCAR5 and OVCAR8,compared with control groups.MTT assays showed that OVCAR5,OVCAR8 and A2780S were differently inhibited in the dose-dependent manner after being treated with different concentrations of AZD6244 (0,2.5,5,10,25,50 and 100 μmol/L,all P<0.05).Further tested by flow cytometry,the results showed that AZD6244 (5,10 μmol/L) was able to induce the apoptosis of OVCAR5,OVCAR8 and A2780S,as well as G0/G1 phase arrest,both in a dose-dependent manner (P<0.05).Conclusions As the main active and functional unit of MAPK/ERK signaling pathway,p-ERK1/2 protein is expressed in both the tissues and various ovarian cancer cell lines.AZD6244 could down-regulated the expression of p-ERK1/2 in ovarian cancer cells,accompanied by the decreased proliferation and increased cell apoptosis of ovarian cancer cells.In conclusion,MAPK/ERK signaling pathway might play a role in the development and progression of ovarian cancer,and may be provide a novel option for molecular targeted therapies of the disease.
9.Expression and significance of IKKεin the specimens and cells of epithelial ovarian cancer
Lu PANG ; Jingchun GAO ; Pengxin ZHANG ; Qian SUN ; Wenjing QI ; Heli GAO ; Hongwei GUAN ; Hong SHI
Chinese Journal of Obstetrics and Gynecology 2017;52(7):483-489
Objective To examine the expressions of IKKε protein in the specimens and cells of epithelial ovarian cancer and investigate the effect of IKKε inhibitor on cell proliferation and apoptosis. Methods (1) A total of 118 cases of patients with the median age of 59 who have accepted surgical treatment due to ovarian cancer in the First Affiliated Hospital of Dalian Medical University from January 2006 to April 2013 were selected. Twenty cases of patients with the median age of 55 who have accepted hysterectomy and salpingo-oophorectomy due to uterine leiomyoma during the same period were selected as the control. The expressions of IKKε protein were detected by immunohistochemistry in normal ovarian tissues and epithelial ovarian cancer specimens,and the relationship between the expressions of IKKε and the clinical features of patients was analyzed. IKKε protein was determined by western blot in various ovarian cancer cells, including SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 treated with or without IKKε inhibitor. The cellular proliferation and apoptosis of ovarian cancer cells after 48 hours treatment of IKKε inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results (1) The immunohistochemical results showed that IKKε was highly expressed in epithelial ovarian cancer specimens with the expression rate 66.1% (78/118), compared with normal ovarian tissue with the expression rate 35.0% (7/20), which exhibited statistically significant difference (χ2=6.993, P=0.008). The expression of IKKε protein was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, the level of CA125 in preoperative serum and distribution of the tumor (P<0.05), but no correlation with age, histological type, the incidence pattern, and tumor size (all P>0.05). (2) IKKε was widely overexpressed in different levels in SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 cells, and the expression of IKKε decreased as the increase of the concentration of IKKε inhibitor (0.1 and 0.5 μmol/L) in OV2008, C13, A2780S, and A2780CP cells after 48 hours treatment. Different concentrations of IKKε inhibitor (0.05, 0.1, 0.5, 1, 5, 10, and 25 μmol/L) significantly inhibited the proliferation of OV2008, C13, A2780S, A2780CP, and SKOV3 cells in a concentration-dependent manner (P<0.05), and the half maximal inhibitory concentration (IC50) was 0.43, 0.86, 0.10, 0.19, and 0.24 μmol/L, respectively. The cell apoptotic rate of OV2008, C13, A2780S, A2780CP, and SKOV3 cells was significantly increased after 48 hours treatment of IKKεinhibitor with the concentration of 0.1 and 0.5 μmol/L (P<0.05). Conclusions The IKKε protein in epithelial ovarian cancer specimens and cells is overexpressed. IKKε inhibitor could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner. Together, the result indicated that IKKε may be a candidate target for the treatment of ovarian cancer in future.
10.Advances in the research on the stature estimation of forensic anthropology
Wei WU ; Lili GUAN ; Peng XIA ; Hongwei LI ; Lihua WAN
Chinese Journal of Forensic Medicine 2017;32(4):368-370,374
Stature is one of the important criteria to individual recognition. And it is always a focus in forensic anthropology. There are some new progresses studies in stature estimation in recent years. We review some studies in stature estimation published in domestic and foreign in the past six years, and find some progresses in stature estimation: (1) As the increasing average human stature, the stature estimation equation is needed to be corrected; (2) Gender, age, race and territory have a great influence to stature estimation. Thus when the study protocol designed, these influences should be considered; (3)The medical imaging technology, especially Computed Tomography, is becoming a new tool to infer stature estimation in forensic anthropology.

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