1.The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer
Qingyi ZHU ; Jianzhong LIN ; Baixin SHEN ; Yong WEI ; Luming SHEN ; Jianguo ZHU ; Xue HE ; Haibin HU ; Min GU
Chinese Journal of Surgery 2024;62(2):162-166
Objective:To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP).Method:This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control.Result:All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 μg/L.Conclusions:The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.
2.PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation
Nuo ZHANG ; Zhen ZHANG ; Yulu ZHANG ; Xue SONG ; Xiaofeng ZHANG ; Jing LI ; Lugen ZUO ; Jianguo HU
Journal of Southern Medical University 2024;44(2):324-332
Objective To investigate the expression of PCI Domain Containing 2(PCID2)in gastric cancer,its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms.Methods We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January,2012 and December,2016,and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients.GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression.The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice.Results PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA(P<0.01).In gastric cancer patients,a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate(P<0.001)as an independent risk factor for postoperative survival(HR:2.987,95%CI:1.616-5.519).The sensitivity,specificity,and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%,75.44%,and 0.755(P<0.001),respectively.GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression.PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation,G1/S phase transition,expressions of cyclin D1 and CDK6,and the growth of transplanted xenograft in nude mice(P<0.05).The expressions of p27 and p16 were significantly lowered in gastric cancer tissues,and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells(P<0.05).Conclusion PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients.High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.
3.Overexpression of BZW1 promotes invasion and metastasis of gastric cancer cells by regulating Wnt/β-catenin signaling and promoting epithelial-mesenchymal transition
Wenjing ZHANG ; Nuo ZHANG ; Zi YANG ; Xiaofeng ZHANG ; Aofei SUN ; Lian WANG ; Xue SONG ; Zhijun GENG ; Jing LI ; Jianguo HU
Journal of Southern Medical University 2024;44(2):354-362
Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.
4.Kuwanon G inhibits growth,migration and invasion of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway
Zhijun GENG ; Jingjing YANG ; Minzhu NIU ; Xinyue LIU ; Jinran SHI ; Yike LIU ; Xinyu YAO ; Yulu ZHANG ; Xiaofeng ZHANG ; Jianguo HU
Journal of Southern Medical University 2024;44(8):1476-1484
Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.
5.Linarin inhibits microglia activation-mediated neuroinflammation and neuronal apoptosis in mouse spinal cord injury by inhibiting the TLR4/NF-κB pathway
Linyu XIAO ; Ting DUAN ; Yongsheng XIA ; Yue CHEN ; Yang SUN ; Yibo XU ; Lei XU ; Xingzhou YAN ; Jianguo HU
Journal of Southern Medical University 2024;44(8):1589-1598
Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.
6.Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms
Xiaohua CHEN ; Hui LU ; Ziliang WANG ; Lian WANG ; Yongsheng XIA ; Zhijun GENG ; Xiaofeng ZHANG ; Xue SONG ; Yueyue WANG ; Jing LI ; Jianguo HU ; Lugen ZUO
Journal of Southern Medical University 2024;44(9):1653-1661
Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.
7.Research progress of autophagy in fibrotic diseases
Ping NIE ; Hu LI ; Hongtao ZHU ; Jianguo HU
Chongqing Medicine 2024;53(9):1406-1411
Fibrosis is a common pathological change in clinical end-stage diseases,which can occur in any organ and is also a major burden of global health care.Persistent fibrosis can lead to organ failure and seri-ously threaten the life and health of patients,but its mechanism is still unclear.With the deepening of the re-search on fibrosis in modern science,the application of single cell genomics has brought new insights into the exploration of fibrosis tissue biology and disease mechanism in clinic.Since the discovery of autophagy,more and more studies at home and abroad have confirmed that autophagy is involved in the occurrence and develop-ment of fibrosis,which provides a new direction for the treatment of organ fibrosis.This article summarizes the effects of autophagy on organs such as lung and uterus,and summarizes the research progress of autoph-agy pathway in organ fibrosis in recent years,in order to provide new ideas for the treatment of organ fibrosis.
8.The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer
Qingyi ZHU ; Jianzhong LIN ; Baixin SHEN ; Yong WEI ; Luming SHEN ; Jianguo ZHU ; Xue HE ; Haibin HU ; Min GU
Chinese Journal of Surgery 2024;62(2):162-166
Objective:To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP).Method:This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control.Result:All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 μg/L.Conclusions:The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.
9.PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation
Nuo ZHANG ; Zhen ZHANG ; Yulu ZHANG ; Xue SONG ; Xiaofeng ZHANG ; Jing LI ; Lugen ZUO ; Jianguo HU
Journal of Southern Medical University 2024;44(2):324-332
Objective To investigate the expression of PCI Domain Containing 2(PCID2)in gastric cancer,its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms.Methods We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January,2012 and December,2016,and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients.GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression.The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice.Results PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA(P<0.01).In gastric cancer patients,a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate(P<0.001)as an independent risk factor for postoperative survival(HR:2.987,95%CI:1.616-5.519).The sensitivity,specificity,and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%,75.44%,and 0.755(P<0.001),respectively.GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression.PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation,G1/S phase transition,expressions of cyclin D1 and CDK6,and the growth of transplanted xenograft in nude mice(P<0.05).The expressions of p27 and p16 were significantly lowered in gastric cancer tissues,and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells(P<0.05).Conclusion PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients.High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.
10.Overexpression of BZW1 promotes invasion and metastasis of gastric cancer cells by regulating Wnt/β-catenin signaling and promoting epithelial-mesenchymal transition
Wenjing ZHANG ; Nuo ZHANG ; Zi YANG ; Xiaofeng ZHANG ; Aofei SUN ; Lian WANG ; Xue SONG ; Zhijun GENG ; Jing LI ; Jianguo HU
Journal of Southern Medical University 2024;44(2):354-362
Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.

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