1.Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer
Feng XU ; Kun XU ; Lingling FAN ; Xintong LI ; Yiqiu LIU ; Fang YANG ; Chengjun ZHU ; Xiaoxiang GUAN
Chinese Medical Journal 2024;137(3):338-349
Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.
2.Characteristics and influencing factors for family resilience among Chinese Army personnel
Shujuan SUN ; Dongxia LIU ; Pingmei LI ; Chengjun DU ; Ke XIONG ; Mengxue ZHAO ; Zhengzhi FENG
Journal of Army Medical University 2024;46(14):1609-1617
Objective To explore the characteristics and influencing factors of family resilience among Chinese PLA Army personnel.Methods A total of 8 094 military personnel subjected with cluster sampling were surveyed with family resilience scale(FRS)and self-designed questionnaire for basic information on military families.Independent sample t test,one-way analysis of variance and step-up regression analysis were employed to analyze the family resilience.Results ① The results of demographic variable analysis showed that there were significant differences in family resilience among the personnel with different marital status,from one-child family or not,birth in rural/urban areas,personnel category,age and education level(P<0.05).② Family factors analysis indicated that different family structure,different family relationships,family rearing styles,recent separation from family members,and frequency of contacting family members had certain effects on family resilience(P<0.05).③ When family relationship,family rearing styles,frequency of contacting family members,birth place,recent separation from family,personnel category,from one-child family,and education level entered the regression equation,the resilience level of army personnel'families was increased by 8.197 for every 1 unit increase in family relationship,and the level of family resilience was increased by 4.688 for every 1 unit increase in family contact frequency(F=202.168,P<0.05).Conclusion The overall level of family resilience of army personnel is good.The risk factors for family resilience are recent separation from their families for ≥1 year,officers,not from only-children family,and the protective factors are harmonious relationship with their families,democratic family rearing style,contacting with their families weekly,urban birth,and bachelor degree or above.
3.Reconstruction points of intrauterine applicator in intracavitary brachytherapy for cervical cancer
Yongfu FENG ; Shaojun CHEN ; Yusong LONG ; Junwen TAN ; Xiantao HE ; Gang LI ; Chengjun FENG ; Zhanyu WANG
Chinese Journal of Radiation Oncology 2024;33(9):825-832
Objective:To evaluate the effect of different reconstruction points of intrauterine applicator on the source dwell positions and plan dosimetry in intracavitary brachytherapy for cervical cancer.Methods:Clinical data of 43 patients with cervical cancer who had completed radical radiotherapy in Liuzhou Workers' Hospital from May 2020 to October 2022 were retrospectively analyzed. Among 43 patients, aged 32-79 years, 40 cases were diagnosed with squamous carcinoma and 3 cases of adenocarcinoma. All patients received external irradiation for 50.4 Gy / 28 fractions and CT-guided intracavitary brachytherapy (45° intrauterine applicator) was 36 Gy / 6 fractions. Brachytherapy was performed by using Fletcher applicator, the curvature of intrauterine applicator were 15°, 30°and45°. Two sets of brachytherapy plans were simulated for each patient. One set of plans extracted the simulated CT positioning images and the original plan of the patient's brachytherapy. The reconstruction point of the curved part of the 45° intrauterine applicator was adjusted to slice-by-slice reconstruction. The plan was optimized to meet clinical requirements according to the prescription, which was called the slice-by-slice group. In the other set of plans, slice-by-slice group was used as a template. The reconstruction points of the curved section of the 45° intrauterine applicator were adjusted to 1, 3, 5, and 7, without modifying the applicator weights and other parameters, which was called the average group 1, 3, 5 and 7. The deviation analysis of 15°, 30° and 45° intrauterine applicator with different number of reconstruction points was carried out, the reconstruction deviation of 45°, 30° and 15° intrauterine applicator at different reconstruction points was compared. Paired-sample t-test or Wilcoxon signed rank test were used to compare the differences in high-risk clinical target volume (HR-CTV) D 50%, D 90%, D 100%, V 100%, V 150%, V 200% and conformity index (CI) as well as D 2 cm3, D 1 cm3 and D 0.1 cm3 in bladder, rectum, and small intestine between two groups of 45° intrauterine applicator. Results:The reconstruction deviation in the average group was mainly from the vertical direction of the 45° intrauterine applicator. The mean reconstruction deviations of 45° (1, 3, 5, 7 reconstruction points), 30° (1, 3, 5 reconstruction points) and 15° (1, 2 reconstruction points) were 1.30 mm, 0.32 mm, 0.14 mm and 0.08 mm; 0.57 mm, 0.14 mm and 0.06 mm; 0.14 mm and 0.06 mm, respectively. There was no significant difference in the parameters of high-risk clinical target volume (HR-CTV) in the slice-by-slice group compared with the average group 5 and 7 (all P>0.005), and no significant difference was found between the average group 5 and 7 (all P>0.005). There were no statistically significant differences in bladder and rectum doses between the slice-by-slice group and the average groups or within the average groups (all P>0.005). The parameters of small intestine in the slice-by-slice group were higher than those of the average group 1, the difference was statistically significant ( P=0.002,<0.001,<0.001). The dose of small intestine in the slice-by-slice group was not statistically significant compared with those in the average group 5 and 7 (both P>0.005). The dose of small intestine in the average group 5 was not statistically significant compared with that in the average group 7 ( P>0.005). The small intestine dose deviations of D 0.1 cm3, D 1 cm3 and D 2 cm3 in the average groups at 1 reconstruction point were 2.41%±1.70%, 1.95%±1.27% and 1.71%±1.10%, respectively. Conclusion:The number of reconstruction points is recommended to be no less than 1, 3 and 5 of the curved part of the 15°, 30°and 45° Fletcher intrauterine applicator, respectively, during intracavitary brachytherapy for cervical cancer.
4.Rac1 promotes the formation of heterotypic cell-in-cell structure.
Tao HU ; Pengfei FENG ; Haoyuan LI ; Lulin ZHOU ; Zubiao NIU ; Yinuo HUANG ; Xiaoning WANG ; Chenxi WANG ; Hui LIU ; Chengjun WU
Chinese Journal of Biotechnology 2023;39(10):4123-4134
Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.
5.Effect of obesity on in-hospital prognosis of patients with mechanical ventilation in PICU
Qin HU ; Chengjun LIU ; Yingfu CHEN ; Fang FANG ; Feng XU
Chinese Pediatric Emergency Medicine 2022;29(3):211-214
Objective:To evaluate the effect of obesity on in-hospital prognosis of patients with mechanical ventilation in PICU.Methods:We enrolled 301 patients who received mechanical ventilation treatment in PICU at Chongqing Medical University Affiliated Children′s Hospital, between June 2015 and June 2020, and stratified them into obese group(49 cases), overweight group(96 cases)and normal weight group(156 cases). Obesity was determined by reference to the growth and development standards published by the World Health Organization.Indicators included PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital and the rates of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers were observed.The influence of obesity on hospitalized prognosis of children in PICU was analyzed.Results:In obesity group, overweight group and normal weight group, PICU hospital mortality(2.0%, 10.4%, 12.2%), the rate of tracheal reintubation(14.3%, 5.2%, 9.0%), the rate of tracheotomy (2.0%, 1.0%, 2.6%), the rate of deep venous thrombosis(8.2%, 3.1%, 5.8%), and the rate of pressure ulcers(4.1%, 7.3%, 1.9%) did not have significant difference(all P>0.05). No ventilator-associated pneumonia and central venous catheter infection occurred in three groups.There were no significant differences in the PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital among the three groups(all P>0.05). Obesity was not an independent risk factor for in-hospital death in PICU patients on mechanical ventilation( B=1.975, SE=1.038, OR=7.206, 95% CI 0.942~55.127, P=0.057). Conclusion:Obesity does not prolong the duration of mechanical ventilation, length of stay in PICU and total length of stay in hospital, as well as not increase the rate of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers.Obesity is not an independent influencing factor for in-hospital death in patients with mechanical ventilation in PICU.
6.Clinical value of lymph node dissection for intrahepatic cholangiocarcinoma
Junwu GUO ; Binghua DAI ; Kunpeng FANG ; Yijun ZHAO ; Zhitao DONG ; Hengmei ZHU ; Chengjun SUI ; Feng XIE ; Li GENG
Chinese Journal of Hepatobiliary Surgery 2022;28(3):202-205
Objective:To evaluate the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC) after surgical resection.Methods:A retrospective study was conducted on the clinical data of 156 patients who underwent surgery for ICC in Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University from November 2010 to December 2017, including 94 males and 62 females, aged (60.0±9.5) years. Curative surgery was performed in 114 cases. Of 64 cases were in stage Ⅰ according to American Joint Committee on Cancer (AJCC), including 38 cases of non-lymph node dissection (NLND) and 26 cases of LND; 21 cases were in AJCC stage Ⅱ, including 11 cases of NLND and 10 cases of LND; 22 cases were in AJCC stage Ⅲb, including 14 cases of LND and 8 cases of lymph node resection (LNR); 5 cases were in AJCC stage Ⅲa, 2 cases were in AJCC stage Ⅳ. Univariate and multivariate Cox regression analysis were used for the risk factors of ICC prognosis. The log-rank test compared the survival rates of the two groups.Results:Cox multivariate analysis indicated that lymph node metastasis was independent risk factors for prognosis in patients with ICC ( HR=1.96, 95% CI: 1.09-3.55, P=0.026). A total of 114 patients were included in the curative surgery group. The 1-, 3-, and 5-year overall survival (OS) rates of the negative lymph node group ( n=91) were 65.9%, 47.3% and 35.6%, respectively, which were significantly better than those of the positive lymph node group ( n=23) who had 1-, 3-, 5-year OS rates of 56.5%, 17.7% and 0, respectively (χ 2=8.11, P=0.004 ). In stage Ⅰ and Ⅱ patients, there were no significant differences in 1-, 3-, 5-year OS rates between the NLND group and the LND group (both P>0.05 ). In stage Ⅲb patients, the LND group had 1-, 3-, 5-year OS rates of 71.4%, 29.8% and 0, respectively, significantly better than those of the LNR group who had 1-, 3-, 5-year OS rates of 37.5%, 0 and 0, respectively (χ 2=6.45, P=0.011). Conclusions:Lymph node metastasis is an independent risk factor affecting the prognosis of ICC. Lymph node dissection should be performed cautiously in ICC with AJCC stage Ⅰ and Ⅱ, while routine lymph node dissection is recommended in ICC with AJCC stage Ⅲb.
7.Efficacy and safety of hydromorphone for postoperative analgesia in children
Yushan GONG ; Dandan PI ; Chengjun LIU ; Jing LI ; Yueqiang FU ; Feng XU
Chinese Pediatric Emergency Medicine 2022;29(11):880-885
Objective:To investigate the efficacy and safety of hydromorphone for postoperative analgesia in children with congenital heart disease, and provide a suitable reference dose for postoperative analgesia in children.Methods:Using a prospective study, 157 patients with congenital heart disease(ASA Ⅱ- Ⅳ) admitted to pediatric intensive care unit at Children′s Hospital of Chongqing Medical University from November 2019 to November 2021 were randomly divided into five groups.Low-dose hydromorphone group (H1 group, 30 cases): hydromorphone dose ≥2 and <3 μg/(kg·h), hydromorphone medium-dose group (H2 group, 30 cases): hydromorphone dose ≥3 and <4 μg/(kg·h), high-dose hydromorphone group (H3 group, 31 cases): hydromorphone dose ≥4 and ≤5 μg/(kg·h), sufentanil group (S group, 36 cases): the dose of sufentanil was 0.08 μg/(kg·h), morphine group (M group, 30 cases): the dose of morphine was 20 μg/(kg·h). The five groups of children received midazolam 2 μg/(kg·min) intravenously at the same time as sedative therapy.Pain score and sedation score were scored at 1 h, 4 h, 8 h, 12 h, and 24 h after operation.Heart rate, mean arterial pressure, blood glucose, lactate, and serum cortisol levels were also monitored and detected, and the occurrence of adverse reactions, the number of cases requiring additional analgesic and sedative drugs, as well as the duration of mechanical ventilation were compared.Results:(1) There were no significant differences regarding the age, body weight, cardiopulmonary bypass time, pediatric critical illness score and ASA score among five groups (all P>0.05). (2) There was no significant difference in the levels of respiration, heart rate, blood sugar, lactate and serum cortisol among five groups after operation.There was no significant difference in preoperative mean arterial pressure among the groups, but there was significant difference in the postoperative mean arterial pressure among the groups at 4 h and 8 h( P<0.05). (3) The analgesic satisfaction of H1 group, H2 group and H3 group at 1 h, 4 h, 12 h and 24 h after operation was significantly higher than that in M group ( P<0.05). There was no significant difference in analgesic satisfaction among H1 group, H2 group and H3 group at each time point.(4) The sedation satisfaction of H1 group, H2 group and H3 group at 4 h and 24 h after operation was significantly higher than that in M group ( P<0.05). There was no significant difference in sedation satisfaction among H1 group, H2 group and H3 group at each time point.(5) There was no significant difference in postoperative analgesia satisfaction and sedation satisfaction between H1 group, H2 group, H3 group and S group.(6) Children in H1 group[1(0, 2)], H2 group[1(0, 2)], H3 group[1(0, 2)] had fewer additional doses within 24 hours than that in M group[2(2, 3)]( P<0.05), and fewer children in H1 group, H2 group and H3 group had been given analgesic sedatives than that in M group ( P<0.05); The extubation time was shortest in H2 group and S group[H2 group(88.3±2.9) h, S group(85.9±3.0) h]. (7) There were no adverse reactions in H1 group, H2 group, H3 group and S group, and there were two cases of apnea in M group. Conclusion:The analgesic effect of hydromorphone in children with congenital heart disease after surgery is better than that of morphine, and the effect of hydromorphone is comparable to that of sufentanil.Hydromorphone 3-4 μg/(kg·h)+ midazolam 2 μg/(kg·min) can achieve satisfactory analgesic and sedative effects in children after congenital heart surgery, with few adverse reactions, safe and reliable, which is an excellent choice for postoperative analgesia and sedation in children.
8.Surgical outcomes of focal cortical dysplasia patients with "difficult to locate" intractable epilepsy and their influencing factors
Chengjun LI ; Feng WANG ; Peisen YAO ; Mingxia XU ; Lianghong YU ; Dezhi KANG ; Yuanxiang LIN
Chinese Journal of Neuromedicine 2021;20(8):793-798
Objective:To explore the surgical outcomes of focal cortical dysplasia (FCD) patients with "difficult to locate" intractable epilepsy and their influencing factors.Methods:Thirty-five FCD patients with "difficult to locate" intractable epilepsy, underwent surgical treatment after intracranial electroencephalogram (iEEG) evaluation in our hospital from January 2011 to December 2018, were chosen in our study. Engel grading was used to evaluate the surgical efficacies of these patients, and they were divided into a satisfied efficacy group (Engel grading I) and an incomplete satisfied efficacy group (Engel grading II-IV). The clinical data of patients from the 2 groups were compared. Multivariate Logistic regression analysis was performed to explore the influencing factors for surgical outcomes of FCD patients with "difficult to locate" intractable epilepsy.Results:Of these 35 patients, 26 patients (74.3%) achieved satisfied efficacy, and 4 had incomplete satisfied efficacy. As compared with those in the satisfied efficacy group, patients in the incomplete satisfied efficacy group had significantly lower total resection rate of epileptogenic foci ( P<0.05). Multivariate Logistic regression analysis showed that incomplete resection of epileptogenic foci was the influencing factor for surgical outcomes of FCD patients with "difficult to locate" intractable epilepsy ( P=0.014, OR=0.050, 95%CI: 0.005-0.547). Conclusion:The FCD patients with "difficult to locate" intractable epilepsy can achieve satisfactory results by surgical resection of epileptogenic zones after iEEG monitoring; these FCD patients with "difficult to locate" intractable epilepsy with incomplete resection of epileptogenic foci often have poor surgical outcomes.
9.Risk factors for mortality in pediatric acute respiratory distress syndrome requiring extracorporeal membrane oxygenation support
Huiling ZHANG ; Zhichun FENG ; Ye CHENG ; Zhe ZHAO ; Yingfu CHEN ; Chengjun LIU ; Dongliang CHENG ; Changsong SHI ; Feng WANG ; Jie WANG ; Youpeng JIN ; Yi YIN ; Guoping LU ; Xiaoyang HONG
Chinese Journal of Pediatrics 2021;59(5):380-386
Objective:To explore the risk factors for mortality in pediatric acute respiratory distress syndrome (PARDS) requiring extracorporeal membrane oxygenation (ECMO) support.Methods:Clinical data of 109 patients with severe PARDS supported by ECMO, who were hospitalized in 6 ECMO centers in China from September 2012 to February 2020, were retrospectively analyzed. They were divided into survival group and death group according to the prognosis. Chi-square test and rank sum test were used to compare the variables between the two groups, including the demographic data, laboratory examination results, clinical data before and after ECMO, and other supportive treatment. Univariate and multivariate Logistic regression models were used to analyze the prognostic risk factors.Results:In these 109 cases, 54 died and 55 survived. Compared with the survival group, the death group had higher incidences of acute kidney injury (AKI) (48.1% (26/54) vs. 21.8% (12/55) , χ2=8.318, P=0.004) and coagulation dysfunction (22.2% (12/54) vs. 7.3% (4/55) , χ2=4.862, P=0.027), and higher rate of renal replacement therapy (48.1% (26/54) vs. 21.8% (12/55) , χ2=9.694, P=0.008) during ECMO support. Logistic regression analysis showed that continuous renal replacement therapy (CRRT) and AKI were independent risk factors for death in patients with severe PARDS requiring ECMO support ( HR=3.88,95% CI 1.04-14.52, HR=4.84,95% CI 1.21-19.46, both P<0.05). Conclusion:AKI and CRRT are independent risk factors for predicting mortality in patients with severe PARDS requiring ECMO support.
10.Characteristics of disturbance coefficient in children without craniocerebral injury at different ages
Han LAI ; Fang FANG ; Wenjun LIU ; Song CHEN ; Chengjun LIU ; Jing LI ; Yueqiang FU ; Ke BAI ; Feng XU
Chinese Journal of Pediatrics 2020;58(4):290-294
Objective:To explore the reference ranges and influential factors of disturbance coefficient (DC) in children without craniocerebral injury at different ages.Methods:Two hundred children without craniocerebral injury admitted to the Department of Orthopaedics in Children′s Hospital of Chongqing Medical University from May 2018 to October 2019 were enrolled in this prospective study. The children were divided into four groups according to age, 0-1 year, >1-3 years, >3-5 years and >5-16 years, each of which included 50 children. Each child had DC measured twice with the non-invasive dynamic cerebral edema monitor, and the average value was used as the terminal DC value. Each measurement lasted 15 minutes, 12 hours apart. The difference of DC values among the four groups and between different genders were compared with ANOVA test and nonparametric test. And the Loess local weighted nonparametric regression analysis was used to explore the change of DC according to the increase of age, weight and head circumference (HC).Results:The reference values of DC for children of 0-1 year,>1-3 years, >3-5 years, and >5-16 years were 60±14, 92±18, 112±18, 135±18, respectively ( F=175.690, P<0.01). There was no statistical significance in DC between male and female children either in the whole or in each separate age group (103 (81, 125) vs. 102 (68, 123) , Z=-0.739, P=0.460; 59 (52, 68) vs. 57 (53, 65) , Z=-0.243, P=0.808; 88 (81, 105) vs. 95 (70, 105) , Z=-0.776, P=0.437; 117 (99, 120) vs. 113 (101, 123) , Z=-0.170, P=0.865; 137 (123, 143) vs. 142 (123, 160) , Z=-1.279, P=0.201). When the child′s age was younger than 5 years, weight was less than 18 kg or HC was less than 51 cm, the DC increased significantly with the increase of age, weight or HC. However, when the age, weight and HC were over the above values, the DC did not show obvious increase, but approaching to stable values of 135, 130, and 130, respectively. Conclusions:For children without craniocerebral injury, the reference values of DC are obviously different at different ages. DC is positively related to age, weight and HC, but not related to gender.

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