1.ADAR1 Regulates the ERK/c-FOS/MMP-9 Pathway to Drive the Proliferation and Migration of Non-small Cell Lung Cancer Cells.
Li ZHANG ; Xue PAN ; Wenqing YAN ; Shuilian ZHANG ; Chiyu MA ; Chenpeng LI ; Kexin ZHU ; Nijia LI ; Zizhong YOU ; Xueying ZHONG ; Zhi XIE ; Zhiyi LV ; Weibang GUO ; Yu CHEN ; Danxia LU ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2025;28(9):647-657
BACKGROUND:
Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.
METHODS:
Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism.
RESULTS:
ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression.
CONCLUSIONS
High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans
;
Lung Neoplasms/physiopathology*
;
Adenosine Deaminase/genetics*
;
Matrix Metalloproteinase 9/genetics*
;
Cell Proliferation
;
Carcinoma, Non-Small-Cell Lung/physiopathology*
;
Cell Movement
;
Animals
;
Mice
;
RNA-Binding Proteins/genetics*
;
Female
;
Male
;
Cell Line, Tumor
;
Proto-Oncogene Proteins c-fos/genetics*
;
Middle Aged
;
MAP Kinase Signaling System
;
Gene Expression Regulation, Neoplastic
;
Mice, Nude
;
Extracellular Signal-Regulated MAP Kinases/genetics*
2.The Performance of Graduation from Traditional Growing Rods with Apical Control Technique in Patients with Congenital Early-Onset Scoliosis
Zhiyi LI ; Yiwei ZHAO ; You DU ; Chenkai LI ; Haoran ZHANG ; Guanfeng LIN ; Yang YANG ; Xiaohan YE ; Shengru WANG ; Jianguo ZHANG
JOURNAL OF RARE DISEASES 2023;2(4):529-538
3.Clinical study on preserving right gastroepiploic vein during laparoscopic right hemicolectomy
Xiaolan YOU ; Yanjun LIAN ; Jian WU ; Yuanjie WANG ; Jiawen DAI ; Xiaojun ZHAO ; Zhiyi CHENG ; Chuanjiang HUANG ; Wenqi LI ; Yan ZHOU
Chinese Journal of Gastrointestinal Surgery 2020;23(12):1164-1169
Objective:The operative approach and steps of laparoscopic right hemicolon cancer radical resection have been standardlized and professional consensus has been reached. However, some detailed issues such as the handling of Henle's trunk and whether to preserve the right gastroepiploic vein (RGEV) still remain controversial. This study investigates the safety, feasibility, short- and long-term outcomes of preserving RGEV during laparoscopic right hemicolectomy.Methods:A retrospective cohort study was carried out. Clinical data of 92 patients undergoing laparoscopic right hemicolectomy in Taizhou People's Hospital from March 2016 to May 2018 were retrospectively analyzed. All the patients were treated with complete mesocolon resection (CME) and had complete postoperative pathological data and follow-up data. Based on the tumor location, 49 patients preserved RGEV (preservation group) and 43 did not (non-preservation group). Pathological data, postoperative complications, short- and long-term outcomes were compared between the two groups.Results:There were no significant differences in baseline data between the two groups (all P>0.05). No significant differences were found in operation time, intraoperative blood loss, unplanned reoperation, anastomotic leak, number of harvested lymph nodes, number of metastatic lymph node, and time to food intake after surgery between two groups (all P>0.05). Compared with non-preservation group, the preservation group had faster recovery of anal gas passage after operation [(3.1±1.0) days vs. (4.0±1.7) days, t=-2.787, P=0.007], shorter length of hospitalization [(11.5±1.5) days vs. (15.0±7.9) days, t=-2.823, P=0.007], and reduced the hospitalization expenses [(46 000±5000) yuan to (57 000±33 000) yuan, t=-2.076, P=0.044]. No postoperative gastroparesis (PGS) occurred in the preservation group, while 6 cases in the non-preservation group developed gastroparesis during perioperative period ( P<0.05). The median time of follow-up time was 31.8 (5.2-43.7) months. The overall survival time of the preservation group and non-preservation group was (35.4±1.8) months and (37.6±1.7) months, respectively without significant difference ( P=0.336); the disease-free survival was (32.0±2.2) months and (35.5±2.0) months, respectively without significant difference as well ( P=0.201). Conclusions:Dissection of the Henle's truck and preservation of RGEV is safe and feasible during laparoscopic right hemicolectomy, which can significantly reduce the incidence of postoperative gastroparesis, shorten the recovery time of postoperative intestinal function and hospitalization, and decrease the cost of hospitalization. The efficacy of RGEV preservation is similar to non-preservation of RGEV.
4.Clinical study on preserving right gastroepiploic vein during laparoscopic right hemicolectomy
Xiaolan YOU ; Yanjun LIAN ; Jian WU ; Yuanjie WANG ; Jiawen DAI ; Xiaojun ZHAO ; Zhiyi CHENG ; Chuanjiang HUANG ; Wenqi LI ; Yan ZHOU
Chinese Journal of Gastrointestinal Surgery 2020;23(12):1164-1169
Objective:The operative approach and steps of laparoscopic right hemicolon cancer radical resection have been standardlized and professional consensus has been reached. However, some detailed issues such as the handling of Henle's trunk and whether to preserve the right gastroepiploic vein (RGEV) still remain controversial. This study investigates the safety, feasibility, short- and long-term outcomes of preserving RGEV during laparoscopic right hemicolectomy.Methods:A retrospective cohort study was carried out. Clinical data of 92 patients undergoing laparoscopic right hemicolectomy in Taizhou People's Hospital from March 2016 to May 2018 were retrospectively analyzed. All the patients were treated with complete mesocolon resection (CME) and had complete postoperative pathological data and follow-up data. Based on the tumor location, 49 patients preserved RGEV (preservation group) and 43 did not (non-preservation group). Pathological data, postoperative complications, short- and long-term outcomes were compared between the two groups.Results:There were no significant differences in baseline data between the two groups (all P>0.05). No significant differences were found in operation time, intraoperative blood loss, unplanned reoperation, anastomotic leak, number of harvested lymph nodes, number of metastatic lymph node, and time to food intake after surgery between two groups (all P>0.05). Compared with non-preservation group, the preservation group had faster recovery of anal gas passage after operation [(3.1±1.0) days vs. (4.0±1.7) days, t=-2.787, P=0.007], shorter length of hospitalization [(11.5±1.5) days vs. (15.0±7.9) days, t=-2.823, P=0.007], and reduced the hospitalization expenses [(46 000±5000) yuan to (57 000±33 000) yuan, t=-2.076, P=0.044]. No postoperative gastroparesis (PGS) occurred in the preservation group, while 6 cases in the non-preservation group developed gastroparesis during perioperative period ( P<0.05). The median time of follow-up time was 31.8 (5.2-43.7) months. The overall survival time of the preservation group and non-preservation group was (35.4±1.8) months and (37.6±1.7) months, respectively without significant difference ( P=0.336); the disease-free survival was (32.0±2.2) months and (35.5±2.0) months, respectively without significant difference as well ( P=0.201). Conclusions:Dissection of the Henle's truck and preservation of RGEV is safe and feasible during laparoscopic right hemicolectomy, which can significantly reduce the incidence of postoperative gastroparesis, shorten the recovery time of postoperative intestinal function and hospitalization, and decrease the cost of hospitalization. The efficacy of RGEV preservation is similar to non-preservation of RGEV.
5. The significance of eosinophils in the correlation of upper and lower airway inflammation in patients with chronic rhinitis
Yong ZHANG ; Wei CHEN ; Junfeng JI ; Zhiyi WANG ; Minghai WU ; You CHENG ; Manjie JIANG ; Qiuping WANG ; Renjie CHEN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2019;54(6):450-455
Objective:
To explore the predictor of lower airway inflammation among the index of nasal inflammation by investigating the expression and association of eosinophils (EOS) in the upper-lower airways and blood of patients with chronic rhinitis.
Methods:
A total of 162 patients with allergic rhinitis (AR), 117 patients with non-allergic rhinitis (NAR) and 104 controls were enrolled from June 2010 to December 2013 from General Hospital of Eastern Theater Command, People′s Liberation Army. All subjects were required detailed medical history collection and nasal resistance measurement. Skin prick test (SPT), blood total immunoglobin E (tIgE) and blood EOS, nasal lavage and induced sputum EOS, nasal provocation and bronchial provocation test (NPT, BPT), nasal and forced exhaled nitric oxide (NNO, FeNO) were performed in all patients. One-way analysis of variance was used for comparison between groups. LSD
6. The role of NF-κB signaling pathway in laryngeal leukoplakia recurrent with laryngeal reflux
Wei CHEN ; Yong ZHANG ; You CHENG ; Zhiyi WANG ; Minghai WU ; Minghui ZHU ; Donghui CHEN ; Hongliang ZHENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2018;53(8):597-603
Objective:
To study the mechanism of vocal mucosal barrier damage mediated by NF-κB and NF-κB-regulated signaling pathway via probing the expression of inflammatory factors and essential proteins for node of NF-κB signaling pathway.
Methods:
The patients suffering from vocal leukoplakia accompanied with larygopharyngeal reflux(LPR) were treated with oral administration of proton pump inhibitor(PPI). Mucosal specimens of vocal cord were collected from all patients before PPI treatment. And the mucosal specimens of vocal cord were collected from the patients with suspected recurrence at 8 weeks after PPI treatment. HE staining was used to observe the histopathological changes of the mucosa. ELISA was utilized to detect the levels of inflammatory factors including tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6. Western blot was used to detect the expression of p-p65, p-IKK and p-IκB. Immunofluorescence method was adopted to detect the entrance of p65 to cell nucleus.Data was analyzed by SPSS 23.0 software.
Results:
In PPI untreated group, the expressions of IL-1β, TNF-α and IL-6 in the specimens of 8 weeks after operation were not different significantly from those obtained during operation.But in the PPI-treated group, the expressions were down-regulated.The expression of p-p65 in the middle and high grade heterogenous hyperplasia group was higher than that of low level heterogenous hyperplasia group.The difference of p65 and p-p65 expression between 8 weeks after surgery and surgery in PPI-untreated group was statistically insignificant (
7.Application of double-pouch anastomosis in laparoscopic radical resection of rectal cancer assisted by small incision.
Xiaolan YOU ; Jian WU ; Yuanjie WANG ; Xiaojun ZHAO ; Yan ZHOU ; Wenqi LI ; Ning XV ; Zhiyi CHENG ; Chuanjiang HUANG ; Guiyuan LIU
Chinese Journal of Gastrointestinal Surgery 2018;21(12):1408-1413
OBJECTIVE:
To explore the feasibility, safety and the economical efficiency of double-pouch anastomosis in laparoscopic radical rectal cancer assisted by small incisions.
METHODS:
Clinical data of 224 patients undergoing gastrointestinal surgery at Taizhou People's Hospital of Jiangsu Province from January 2011 to December 2017 were retrospectively analyzed. Indusion criteria: patients were diagnosed as primary rectal adenocarcinoma by preoperative enteroscopy pathology, the distance of the tumor to anal margin was from 4 to 15 cm, and patients were treated with laparoscopic total mesorectal excision(TME) through small incision. Patients were divided into two groups according to different anastomosis method, double-pouch group(108 cases) and single-pouch group (116 cases). The surgical indexes, tumor safety indexes, short-term efficacy and economic indexes were compared between the two groups.
RESULTS:
There was no significant difference between two groups in baseline data, operative time, blood loss, number of lymph nodes dissection, average length of proximal and distal bowel, or incidence of urination and sexual dysfunction (all P>0.05). Compared with the single-pouch group, the double-pouch group presented lower anastomotic secondary bleeding rate [0.9%(1/108) vs. 6.0% (7/116), χ²=4.238, P=0.040], lower incidence of anastomotic leakage[1.9%(2/108) vs. 7.8%(9/116), χ²=4.179, P=0.041], lower incidence of anastomotic stricture [1.9% (2/108) vs. 8.6% (10/116), χ²=5.054, P=0.025], shorter hospital stay [(13.4±3.9) days vs. (15.9±9.8) days, t=2.524, P=0.013] and less average hospitalization costs [(34 000±7 000) yuan vs. (46 000±23 000) yuan, t=5.047,P<0.001]. There was no significant difference in local recurrence, distant metastasis or overall survival between the two groups during mean follow-up of 33 months (all P>0.05).
CONCLUSION
Laparoscopic TME assisted by small incision with double-pouch anastomosis is a safe, feasible and economical method.
Anastomosis, Surgical
;
standards
;
Humans
;
Laparoscopy
;
Rectal Neoplasms
;
surgery
;
Retrospective Studies
;
Treatment Outcome
8.Clinical study of preserving left colic artery during laparoscopic total mesorectal excision for the treatment of rectal cancer.
Xiaolan YOU ; Yuanjie WANG ; Zhiyi CHEN ; Wenqi LI ; Ning XU ; Guiyuan LIU ; Xiaojun ZHAO ; Chuanjiang HUANG
Chinese Journal of Gastrointestinal Surgery 2017;20(10):1162-1167
OBJECTIVETo evaluate the feasibility, safety, radicality and short-term outcome of preserving left colic artery (LCA) during laparoscopic total mesorectal excision (TME) for the treatment of rectal cancer.
METHODSFrom January 2013 to December 2016,136 patients with mid-lower rectal cancer received laparoscopic TME in the Gastrointestinal Surgery Department of Taizhou People's Hospital of Jiangsu Province. Patients with rectal tumor within 10 cm to the anal verge were enrolled into the study. All the enrolled patients had complete data of pathology and follow-up. Those receiving neoadjuvant chemoradiotherapy, with severe base diseases, multifocal tumor, tumor invasion of surrounding tissues, fixation of tumor, recurrent tumor, complications such as acute ileus, bleeding, perforation were excluded. In this study, 72 patients did not undergo preservation of LCA (high ligation group) and 64 patients underwent preservation of LCA (low ligation group). Operative parameters, clinicopathological data and short-term outcome were collected and compared between two groups.
RESULTSThe baseline data including gender, age, body mass index, tumor stage, and distance of tumor from anal verge of two groups were comparable (P>0.05). The differences between two groups about the mean time of operation and the operative blood loss were not significant [(164.0±12.6) min vs. (167.3±9.4) min, (30.0±3.6) ml vs. (30.1±3.0) ml, all P>0.05]. There was no operative death in both groups. Differences in the lymph node dissection (13.7±2.6 vs. 13.3±2.1) and the specimen length of proximal resection margin [(16.4±1.9) cm vs. (16.7±2.1) cm] or distal resection margins [(3.9±0.6) cm vs. (4.1±0.9) cm] between high and low ligation groups were not significant (all P>0.05). Compared with high ligation group, the low ligation group had higher rate of sphincter preservation [92.2% (59/64) vs. 79.2% (57/72), χ=4.580, P=0.032], lower rate of anastomotic leakage [1.6% (1/64) vs. 9.7% (7/72), χ=4.075, P=0.044], anastomotic stenosis [3.1% (2/64) vs. 12.5%(9/72), χ=4.006, P=0.045], and voiding and sexual dysfunction [6.3%(4/64) vs. 18.1%(13/72), χ=4.317, P=0.038]. Mean time of follow-up was 19 months. In high ligation group, the local recurrent rate was 5.56%, distant metastasis rate was 13.89%, overall survival rate was 90.28%, disease-free survival rate was 80.56%, while in low ligation group, the local recurrence rate was 4.69%, distant metastasis rate was 12.50%, overall survival rate was 90.63%, disease-free survival rate was 82.81%, whose differences between two groups were not significant (all P>0.05).
CONCLUSIONPreservation of LCA during laparoscopic TME for the treatment of rectal cancer is safe and feasible, which can reduce the incidence of anastomotic leakage and stenosis, and voiding and sexual dysfunction.
9.Clinical significance of No.12 lymph node dissection for advanced gastric cancer.
Xiaolan YOU ; Yuanjie WANG ; Wenqi LI ; Xiaojun ZHAO ; Zhiyi CHENG ; Ning XU ; Chuanjiang HUANG ; Guiyuan LIU
Chinese Journal of Gastrointestinal Surgery 2017;20(3):283-288
OBJECTIVETo evaluate the clinical significance of No.12 lymph node dissection for advanced gastric cancer with D2 lymphadenectomy.
METHODSClinicopathologic data and No.12 lymph node dissection of 256 advanced gastric cancer patients undergoing radical operation in our department between January 2005 and December 2010 were retrospectively summarized and the influence factors of metastasis in No.12 lymph nodes were analyzed.
RESULTSOf 256 patients, 179 were male and 77 were female with the average age of 59.2 years. Tumor located in the upper of stomach in 24 cases, middle of stomach in 41 cases, lower of stomach in 174 cases, multi-focus or diffuse distribution of stomach in 17 cases. Tumor diameter was <3 cm in 39 cases, 3 to 5 cm in 100 cases, >5 cm in 117 cases. Serum carcinoembryonic antigen (CEA) level increased in 61 cases, serum carbohydrate antigens (CA)72-4 increased in 56 cases and CA19-9 increased in 61 cases. The number of No.12 lymph nodes resected from all the patients was 1 152, and the average number was 4.5±1.9. The metastasis rate of No.12 lymph nodes was 9.4%(24/256) after hematoxylin eosin staining (positive group). All the patients received effective follow-up to December 2015, and the average follow-up time was 101.2 months. The median survival time of positive No.12 group (24 cases) was 29.8 months and of negative No.12 group (232 cases) was 78.2 months, whose difference was statistically significant (χ=21.715, P=0.000). Univariate analysis found that No.12 lymph node metastasis was not associated with age, gender, tumor differentiation (all P>0.05), but was associated with tumor location, tumor diameter, invasive depth (all P<0.05), and was closely associated with Borrmann type, outside metastatic lymph nodes of No.12 and high levels of serum CEA, CA72-4 and CA19-9 (all P=0.000). Multivariate regression analysis found that tumor location (RR=2.452, 95%CI:1.537 to 3.267, P=0.000), Borrmann type (RR=1.864, 95%CI:1.121 to 3.099, P=0.016) and number of outside metastatic lymph nodes of No.12 (RR=2.979, 95%CI: 2.463 to 3.603, P=0.000) were the independent risk factors of the No.12 metastasis (P<0.05).
CONCLUSIONSMetastasis in No.12 lymph nodes indicates poorer prognosis. The No.12 lymph nodes of advanced gastric cancer patients with curative resection, especially those with the tumor located in the lower part, Borrmann type IIII(, outside metastatic lymph nodes of No.12, should be regularly cleaned.
Antigens, Tumor-Associated, Carbohydrate ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; methods ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; diagnosis ; pathology ; physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; statistics & numerical data ; Neoplasm Invasiveness ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; blood ; mortality ; pathology ; Survival Rate
10.Unidirectional barbed suture used in laparoscopic transabdominal preperitoneal hernia repair
Chuanjiang HUANG ; Xiaojun ZHAO ; Ning XU ; Zhiyi CHENG ; Guiyuan LIU ; Xiaolan YOU ; Yuanjie WANG
Chinese Journal of General Practitioners 2017;16(11):884-886
The clinical data of 42 patients undergoing laparoscopic transabdomical preperitoneal ( TAPP) hernia repair in Taizhou People′s Hospital from January 2015 to June 2016 were retrospectively analyzed.In this series, 22 patients used VicrylTM polyglactin suture (group A) and 20 patients used the unidirectional barbed suture (group B).The clinical efficacy and postoperative complications were compared between the two groups.There were no significant differences in volume of intraoperative blood loss [(7.3 ± 3.2) vs.(7.9 ±3.2)ml],length of postoperative hospital stay [(14.6 ±1.2) vs.(4.8 ±1.1)d], pain scores [visual analogue scale (VAS),1.9 ±0.9 vs.2.1 ±1.0] at the first-day after operation,body discomfort(1 vs.0 case),and incidence of chronic pain and recurrence between the two groups (P>0.05). The time of operation and peritoneum suturation in group B was markedly shorter than that in group A [(34.3 ±7.1) vs.(40.4 ±9.9) min, (9.8 ±1.8) vs.(13.1 ±4.8) min, both P <0.05].Both unidirectional barbed suture and VicrylTM polyglactin suture are safe ,effective in peritoneum suturation for inguinal hernia repair; however , the unidirectional barbed suture has advantages of shorter operation time and less difficulty of surgical procedure .

Result Analysis
Print
Save
E-mail