1.Circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2
Junxiu ZHAO ; Yi ZHU ; Xiaoyu SONG ; Chao ZHE ; Yuhan XIAO ; Yunduo LIU ; Linhai LI ; Bin XIAO
China Oncology 2024;34(10):915-930
Background and purpose:Human epidermal growth factor receptor 2(HER2)serves as one of the paramount drivers of breast cancer metastasis,with roughly 20%-30%of breast cancer patients exhibiting high expression of HER2.The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells;however,the manner in which HER2 expression is modulated at the mRNA level remains ambiguous.Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2,and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported.This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression.Methods:In this study,a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells.RNA fluorescence in situ hybridization(FISH)was utilized to detect the subcellular localization of circ-0007766.The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance.Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro.The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments,and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured.Additionally,it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972.A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972.The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment.RIP detection was performed in MDA-MB-231 cells,and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).Western blot was used to detect the protein expressions.Results:Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells,with the preponderance being in the cytoplasm.The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues.The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples.The overexpression(knockdown)of circ-0007766 in HER2-negative breast cancer cells(in HER2-positive breast cancer cells)was capable of promoting(inhibiting)the migration and invasion of breast cancer cells.Circ-0007766 directly bound to miR-1972,which inhibited breast cancer cell migration and invasion,thereby forming an endogenous competitive RNA(ceRNA)regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972.Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972.CircRNAs sequestered miRNAs to function as ceRNAs,thereby regulating gene expression at both the transcriptional and translational levels.Finally,we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples,while the expression levels of miR-1972 and HER2 were negatively correlated.Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression.Conclusion:This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis,offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.
2.Fixation with a retrograde pubic ramus intramedullary nail for anterior pelvic ring fractures
Enzhi YIN ; Yangxing LUO ; Xuefeng YUAN ; Li HE ; Meiqi GU ; Jie XIE ; Song GONG ; Zhen WANG ; Zhe XU ; Penghui XIANG ; Ruixiang CHENG ; Chengla YI
Chinese Journal of Orthopaedic Trauma 2023;25(6):491-497
Objective:To explore the clinical efficacy of a retrograde pubic ramus intramedullary nail (RPRIN) in the treatment of anterior pelvic ring fractures.Methods:A retrospective study was conducted to analyze the 14 patients with anterior pelvic ring fracture who had been treated and followed up at Department of Traumatic Surgery, Tongji Hospital From June 2020 to February 2021. There were 10 males and 4 females with an age of (44.8±12.5) years. By the AO/OTA classification for pelvic fractures, 5 cases were type 61-A, 4 cases 61-B, and 5 cases type 61-C; by the Nakatani classification, 1 case belonged to unilateral zone Ⅰ fracture, 5 cases to unilateral zone Ⅱ fracture, 2 cases to unilateral zone Ⅲ fracture, 3 cases to right zone Ⅱ and left zone Ⅲ fracture, 2 cases to zone Ⅲ fracture on both left and right sides, and 1 case to zone Ⅱ fracture on both sides. The time from injury to operation was (7.8±1.8) days. All the anterior pelvic ring fractures were fixated with a RPRIN. The time and fluoroscopic frequency for placement of every single RPRIN, quality of fracture reduction, and pelvic function and incidence of postoperative complications at the last follow-up were recorded.Results:A total of 18 RPRINs were placed in the 14 patients. For placement of each RPRIN, the time was (35.9±8.6) min, and the fluoroscopic frequency (22.8±1.9) times. No complications such as infection occurred at any surgical incision after RPRIN placement. According to the Matta scoring, the quality of postoperative fracture reduction was assessed as excellent in 7 cases, as good in 5 cases and as fair in 2 cases. The 14 patients were followed up for (18.1+1.5) months. Their X-ray and CT images of the pelvis at the last follow-up showed that the fractures healed well and the intramedullary nails were placed in the cortical bone of the anterior ring of the pelvis. According to the Majeed scoring at the last follow-up, the pelvic function was assessed as excellent in 10 cases, as good in 3 cases and as fair in 1 case. One patient reported discomfort during squatting 2 months after operation but the symptom improved 3 months later without any special treatment. No patient experienced such complications as displacement or slippage of RPRIN, or pain at the insertion site.Conclusion:RPRIN is effective in the treatment of anterior pelvic ring fractures, showing advantages of small surgical incision, limited intraoperative fluoroscopy and short operation time.
3.Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma.
Chang Ning ZHANG ; Xiao Yang LIU ; Qing LI ; Yi Zhe SONG ; Bin LIU ; Jian YIN ; Jing Hong YANG ; Li ZHONG ; Li SUN ; Xun ZHANG ; Wen CHEN
Chinese Journal of Oncology 2023;45(5):402-409
Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.
Female
;
Humans
;
Papillomavirus Infections/diagnosis*
;
Retrospective Studies
;
Uterine Cervical Neoplasms/pathology*
;
Prognosis
;
Oncogene Proteins, Viral/genetics*
;
Human Papillomavirus Viruses
;
Adenocarcinoma/pathology*
;
RNA, Messenger/genetics*
;
Papillomaviridae/genetics*
;
RNA, Viral/genetics*
4.Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms.
Ying HAO ; Li Na WU ; Yi Tong LYU ; Yu Zhe LIU ; Xiao Song QIN ; Rui ZHENG
Chinese Journal of Preventive Medicine 2023;57(11):1827-1838
Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.
Humans
;
Carcinoma, Non-Small-Cell Lung/surgery*
;
Lung Neoplasms/diagnosis*
;
Retrospective Studies
;
Autoantibodies
;
Bayes Theorem
;
Tumor Suppressor Protein p53
;
Carcinoembryonic Antigen
;
Antigens, Neoplasm
;
Biomarkers, Tumor
;
Algorithms
;
Pneumonia
5.Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms.
Ying HAO ; Li Na WU ; Yi Tong LYU ; Yu Zhe LIU ; Xiao Song QIN ; Rui ZHENG
Chinese Journal of Preventive Medicine 2023;57(11):1827-1838
Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.
Humans
;
Carcinoma, Non-Small-Cell Lung/surgery*
;
Lung Neoplasms/diagnosis*
;
Retrospective Studies
;
Autoantibodies
;
Bayes Theorem
;
Tumor Suppressor Protein p53
;
Carcinoembryonic Antigen
;
Antigens, Neoplasm
;
Biomarkers, Tumor
;
Algorithms
;
Pneumonia
6.Phenotypes and genotypes of 78 patients with propionic acidemia.
Xue MA ; Yi LIU ; Zhe Hui CHEN ; Yao ZHANG ; Hui DONG ; Jin Qing SONG ; Ying JIN ; Meng Qiu LI ; Lu Lu KANG ; Ru Xuan HE ; Yuan DING ; Dong Xiao LI ; Hong ZHENG ; Li Ying SUN ; Zhi Jun ZHU ; Yan Ling YANG ; Yongtong CAO
Chinese Journal of Preventive Medicine 2022;56(9):1263-1271
Objective: Propionic acidemia is a rare inherited metabolic disorder caused by propionyl CoA carboxylase (PCC) deficiency. This study aims to analyze the clinical characteristics and gene variations of Chinese patients with propionic acidemia, and to explore the correlation between clinical phenotypes and genotypes. Methods: Single-center, retrospective and observational study. Seventy-eight patients of propionic acidemia (46 males and 32 females) from 20 provinces and autonomous regions were admitted from January 2007 to April 2022. Their age of initial diagnosis ranged from 7 days to 15 years. The clinical manifestations, biochemical and metabolic abnormalities, genetic variations, diagnosis, treatment and outcome were studied. Chi-Square test or Mann-Whitney U test were used for statistical analysis. Results: Among 78 cases, 6 (7.7%) were identified by newborn screening; 72 (92.3%) were clinically diagnosed after onset, and the age of onset was 2 hours after birth to 15 years old; 32 cases had early-onset disease and 40 cases had late-onset disease. The initial manifestations included lethargy, hypotonia, vomiting, feeding difficulties, developmental delay, epilepsy, and coma. Among the 74 cases who accepted gene analysis, 35 (47.3%) had PCCA variants and 39 (52.7%) had PCCB variants. A total of 39 PCCA variants and 32 PCCB variants were detected, among which c.2002G>A and c.229C>T in PCCA and c.838dupC and c.1087T>C in PCCB were the most common variants in this cohort. The variants c.1228C>T and c.1283C>T in PCCB may be related to early-onset type. The variants c.838dupC, c.1127G>T and c.1316A>G in PCCB, and c.2002G>A in PCCA may be related to late-onset disease. Six patients detected by newborn screening and treated at asymptomatic stage developed normal. The clinically diagnosed 72 cases had varied complications. 10 (12.8%) cases of them died. 62 patients improved after metabolic therapy by L-carnitine and diet. Six patients received liver transplantation because of recurrent metabolic crisis. Their clinical symptoms were markedly improved. Conclusion: The clinical manifestations of propionic acidemia are complex and lack of specificity. Newborn screening and high-risk screening are keys for early treatment and better outcome. The correlation between the genotype and phenotype of propionic acidemia is unclear, but certain variants may be associated with early-onset or late-onset propionic acidemia.
Carnitine
;
Female
;
Genotype
;
Humans
;
Male
;
Methylmalonyl-CoA Decarboxylase/metabolism*
;
Mutation
;
Phenotype
;
Propionic Acidemia/genetics*
;
Retrospective Studies
7.Sacral osteotomy combined with triangular osteosynthesis in the treatment of malunion or nonunion of vertically displaced pelvic fractures
Meiqi GU ; Yangxing LUO ; Li HE ; Yue LI ; Jie XIE ; Song GONG ; Qian ZHANG ; Enzhi YIN ; Zhe XU ; Xiangjun BAI ; Chengla YI ; Hua CHEN
Chinese Journal of Orthopaedics 2022;42(20):1358-1365
Objective:To investigate the clinical therapy of sacral osteotomy combined with lumbopelvic distraction triangular osteosynthesis for malunion and nonunion of type C longitudinally displaced sacral fracture.Methods:A retrospective study of 9 patients with malunion and nonunion of type C pelvic fractures who had been treated with sacral osteotomy combined with triangular osteosynthesis from April 2015 to January 2020 were analyzed. They were 5 men and 4 women, with an average age of 30.67±10.06 (range 14-45 years). AO/OTA classification at initial pelvic fracture, 8 cases were type C1.3 and one was type C3.3. The period from injury to surgery was 12.8±18.92 months (range 3-60 months). The cranial displacement of one side of the pelvis was 3.8±0.57 cm (range 2.5-4.1 cm). Sacral osteotomy and triangular osteosynthesis were used in all nine patients, combined with osteotomy or no osteotomy of the superior and inferior branches of the anterior ring pubis. The degree of longitudinal displacement of one side of the pelvis was assessed by making a vertical line gap between the acetabular apex on both sides and the central axis of the sacrum on the X-ray of the pelvis. The Majeed scoring and visual analogue scale (VAS) were evaluated preoperatively and at the last follow-up to assess the therapeutic effect of the patients.Results:In all 9 patients, except for 1 case of postoperative pelvic residual displacement 1.5 cm (preoperative 3.2 cm difference compared with the healthy side), the other 8 patients had a postoperative bilateral difference of 0.1-0.7 cm. All the patients were followed up for 12.00±9.95 months. At the last follow-up, the Majeed score of pelvic fracture increased from 44.0(33.5, 76.0) points preoperatively to 91.0(80.5, 92.5) points. The difference before and after operation was statistically significant ( Z=2.67, P<0.001), and the gait was significantly improved. And the VAS score for pain decreased from 6.00±1.41 points preoperatively to 1.22±0.97 points. The difference before and after operation was statistically significant ( t=8.73, P<0.001). None had complications like infection, plate broken, screw loosening, iatrogenic nerve or blood vessel injury, etc. Conclusion:Sacral osteotomy combined with lumbopelvic distraction triangular osteosynthesis for the treatment of pelvic malunion and nonunion caused by sacral fracture can correct pelvic deformity, prolong limb length, and reconstruct the stability of pelvic ring with good clinical results.
8.Methylated CpG dinucleotides in the 5-α reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients.
Zhe-Min LIN ; Dong-Dong FAN ; Song JIN ; Zhan-Liang LIU ; Yi-Nong NIU
Asian Journal of Andrology 2021;23(3):266-272
The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0-100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from -400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.
9.Application of a new V-shaped forearm flap in reconstruction of buccal cancer
Shengwei HAN ; Hao LI ; Rui LIU ; Chuanhui SONG ; Xiteng YIN ; Zhe LIU ; Yi LIANG ; Wei HAN
Chinese Journal of Microsurgery 2021;44(3):279-282
Objective:To design a new V-shaped forearm flap and to investigate the possibility of direct donor site closure and its value in the reconstruction of soft tissue defect after resection of buccal carcinoma.Methods:The new V-shaped forearm flap technique was applied in 10 patients with buccal carcinoma from October, 2018 to September, 2019. There were 6 males and 4 females aged from 35 to 63 years (48.3 years in average). Flap size ranged from 3.0 cm×5.0 cm to 4.0 cm×6.0 cm. Wound healing and the appearance forearm were recorded and evaluated three months after the surgery. Radial deviation angle, wrist flexion, ulnar deviation and dorsal extension were measured and calculated 3 months after the surgery. The wrist function was evaluated according to the Gartland-Werley scale. The recovery of wrist function was evaluated by comparing with the preoperative data.Results:Forearm donor sites were successfully closed without skin grafting in all 10 patients. Skin ischemia caused by excessive tension was observed at the incision edge in 3 patients, therefore leading to skin exfoliation and pigment loss without affecting wound healing. All patients were presented a cosmetic outcome during the follow-up period. No scar hyperplasia was observed. No significant difference was observed in perioperative wrist flexion angle, dorsal extension angle, radial deviation angle, ulnar deviation angle ( P>0.05)[data before surgery were (57.8±1.3) °, (58.4±0.7) °, (18.2±0.5) °, (28.5±1.1) ° respectively, and data 3 months after surgery were (53.2±2.1) °, (55.3±1.8) °, (16.4±0.4) °, (25.4±1.4) ° respectively]; Excellent and good rate of Gartland-Werley wrist score before and after surgery were both 100%. Conclusion:The new V-shaped free forearm flap can directly close small to medium forearm flap donor site. This method could avoid the trauma and complications of traditional free skin graft. The postoperative appearance on donor site is satisfactory and will not have adverse effects on wrist function. The new V-shaped free forearm flap is a novel method for repair of the defect of soft tissue defect after buccal cancer and it is worth to be applied in clinical practice.
10.Endoscopic lateral neck dissection via the breast and transoral approaches for papillary thyroid carcinoma: a report of 10 cases.
Guo Yang WU ; Jin Bo FU ; Ye Zhe LUO ; Wei YAN ; Xiao Quan HONG ; Peng Hao KUANG ; En De LIN ; Fu Sheng LIN ; Zheng Fu SONG ; Ji Yu CHEN ; Yi Long FU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(7):751-754
Objective: To investigate the feasibility of endoscopic lateral neck dissection via the breast and transoral approaches (ELNDBTOA) for papillary thyroid carcinoma (PTC). Methods: From February 2015 to April 2019, 10 patients with PTC (cN1b) including 1 male and 9 females aged from 22 to 53 years old received ELNDBTOA in the General Surgery Department of Zhongshan Hospital, Xiamen University. Total thyroidectomy, the central lymph node dissection and the selective neck dissection (levels Ⅱ, Ⅲ and Ⅳ) were performed endoscopically via the breast approach, and then the residual lymph nodes were dissected via transoral approach. The medical records, operation time, blood loss, complications and postoperative follow-up outcomes were analyzed retrospectively. SPSS 22.0 software package was used for statistical processing of clinical data of patients. Results: All cases were successfully treated with ELNDBTOA without transfer to open surgery. The average operative time was (362.5±79.7) min, the blood loss was (23.0±14.9) ml, and the postoperative hospital stay was (5.1±1.3) days. The mean number of harvested cervical lymph nodes were (34.2±25.8), and the mean number of positive lymph nodes were (6.5±4.9). Lymph nodes were dissected by the further dissection via oral approach in 6 patients and a total of 9 lateral lymph nodes were havested from 2 of the 6 patients, with 3 positive lymph nodes. Two patients had transient skin numbness in the mandibular area and recovered within two weeks. One patient developed transient hypoparathyroidism and recovered within two months. No secondary bleeding, recurrent laryngeal nerve paralysis, chylous leakage, neck infection, permanent hypoparathyroidism or other complications were observed. The follow-up time was from 16 to 66 months with a median of 42.5 months, no tumor recurrence or metastasis occurred, and also no obvious deformity, abnormal sensation or movement in the chest, neck and mouth was observed. Conclusions: ELNBTOA is safe and feasible, with good cosmetic outcome.
Adult
;
Female
;
Humans
;
Lymph Nodes
;
Male
;
Middle Aged
;
Neck Dissection
;
Retrospective Studies
;
Thyroid Cancer, Papillary/surgery*
;
Thyroid Neoplasms/surgery*
;
Thyroidectomy
;
Young Adult

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