1.Effects of insulin-like growth factor-1 on the mechanism of myopia-related factors secreted by human scleral fibroblasts
Rongrong CHAO ; Zhixiang DING ; Jing FAN ; Liu ZHENG
International Eye Science 2025;25(2):198-205
AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.
2.Effect of thrombocytosis on prognosis of hepatocellular carcinoma after TACE
Tingsong YING ; Hao XU ; Zichen WU ; Zhixiang FAN ; Wang LIU
Chinese Journal of Hepatobiliary Surgery 2024;30(1):15-20
Objective:To analyze the prognosis of hepatocellular carcinoma (HCC) patients with thrombocytosis (platelet count ≥350×10 9) after transcatheter arterial chemoembolization (TACE), and the effect of thrombocytosis on the prognosis of patients with HCC after TACE. Methods:Clinical data of 867 patients with HCC admitted to the Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2013 to May 2018 were retrospectively analyzed. After propensity score matching, 99 patients were enrolled, including 70 males and 29 females, aged (60.1±12.1) years. Patients were divided into the groups with thrombocytosis ( n=33) and without thrombocytosis ( n=66). The gender, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, and total bilirubin were compared between the two groups. The association of thrombocytosis with the prognosis of HCC after TACE treatment were analyzed using univariate and multivariate Cox regression. Results:After propensity score matching, the male proportion, maximum tumor diameter, BCLC stage, and serum level of total bilirubin were comparable between the groups (all P>0.05). Before TACE treatment, the platelet count of patients with thrombocytosis was (394.4±54.5)×10 9/L, which was higher than that after TACE [(278.2±86.4)×10 9/L, t=7.63, P<0.001]. The progression-free survival rates after TACE in without thrombocytosis group were 83.3%, 24.2%, and 7.6% at 3, 6 and 9 months, respectively, better than those in thrombocytosis group (51.5%, 3.0%, and 3.0%, respectively; χ2=31.24, P<0.001). The overall survival rates after TACE in without thrombocytosis group were 81.8%, 30.3%, and 4.5% at 1, 2 and 3 years, respectively, better than those in thrombocytosis group (15.2%, 9.1%, and 3.0%, respectively; χ2=27.89, P<0.001). Multivariate Cox regression analysis showed that patients of HCC with thrombocytosis had an increased risk of tumor progression ( HR=5.785, 95% CI: 3.291-10.168, P<0.001) and increased risk of death ( HR=4.090, 95% CI: 2.482-6.740, P<0.001) after TACE. Conclusion:The prognosis of TACE for HCC might be worse in patients with thrombocytosis. Thrombocytosis is a risk factor for cumulative survival and progression-free survival of HCC patients after TACE.
3.Correlation analysis of preoperative red blood cell distribution width and prognosis of patients undergoing TACE for hepatocellular carcinoma
Tingsong YING ; Zhixiang FAN ; Hao XU ; Wang LIU ; Rujian WANG ; Qingqiao ZHANG ; Ning WEI ; Yanfeng CUI ; Hongtao LIU
Chinese Journal of Hepatobiliary Surgery 2024;30(3):166-170
Objective:To evaluate the relationship between red blood cell distribution width (RDW) and prognosis of patients with hepatocellular carcinoma (HCC) andergoing transcatheter arterial chemoembolization (TACE).Methods:Clinical data of 212 patients with HCC andergoing TACE for the first time in Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2011 to May 2018 were retrospectively analyzed, including 184 males and 28 females, aged (56.8±11.2) years. Follow-up for survival. X-tile software was used to determine 13.1% as the optimal threshold for preoperative RDW prediction of prognosis, and enrolled patients were divided into a low level group (RDW<13.1%, n=70) and a high level group (RDW≥13.1%, n=142). Aspartate aminotransferase, total bilirubin, albumin, hemoglobin and lipoprotein a, Barcelona clinical liver cancer (BCLC) stage and other indexes were compared between the two groups. Survival analysis was performed by Kaplan-Meier method, survival rate was compared by log-rank test, and the effect of RDW on prognosis was analyzed by Cox regression. Results:The 1-year, 2-year and 3-year cumulative survival rates in RDW high level group were 34.5%, 14.1% and 6.3%, respectively, while those in RDW low level group were 64.3%, 38.6% and 21.4%, respectively, with significant difference ( χ2=23.09, P<0.001). Compared with the low level group, the levels of aspartate aminotransferase and total bilirubin were higher, the levels of albumin, hemoglobin and lipoprotein a were lower, the proportion of portal vein cancer thrombin was higher, and the stage of BCLC was later, with statistical significance (all P<0.05). Cox regression analysis showed that HCC patients with RDW≥13.1%( HR=1.732, 95% CI: 1.223-2.452, P=0.002) had poor survival prognosis after TACE. Conclusion:Preoperative RDW≥13.1% is an independent risk factor for survival after TACE in patients with HCC. RDW has potential predictive value for prognosis of patients with HCC.
4.Clinical analysis of early Klebsiella pneumoniae infection after liver transplantation
Kezhong ZHENG ; Song CHEN ; Zhixiang HE ; Guobin WANG ; Hongchuan ZHAO ; Xiaoping GENG ; Fan HUANG
Organ Transplantation 2024;15(5):805-815
Objective To identify early Klebsiella pneumoniae(KP)infection after liver transplantation and its impact on prognosis.Methods Clinical data of 171 liver transplant recipients were retrospectively analyzed,and they were divided into the non-infection(n=52)and infection groups(n=119)according to the bacterial culture results at postoperative 2 weeks.In the infection group,KP was not detected in 86 cases(non-KP infection group),and KP was cultured in 33 cases(KP infection group).Preoperative,intraoperative and postoperative data were statistically compared between the non-infection and infection groups,and between the non-KP infection and KP infection groups.The risk factors of early KP infection after liver transplantation and the influencing factors of long-term survival of the recipients were analyzed.Results Compared with the non-infection group,model for end-stage liver disease(MELD)score and total bilirubin level were higher,the operation time was longer,the length of postoperative intensive care unit(ICU)stay and the length of hospital stay were longer,the amount of intraoperative red blood cell transfusion was higher,the hospitalization expense was higher,the incidence of severe complications was higher,white blood cell count,absolute neutrophil cell count and neutrophil-to-lymphocyte ratio at postoperative 14 and 30 d were higher,absolute lymphocyte count at postoperative 14 d was lower and hemoglobin level at postoperative 30 d was lower in the infection group.The differences were statistically significant(all P<0.05).Compared with the non-KP infection group,MELD score,total bilirubin level and aspartate aminotransferase(AST)level were higher,the operation time and the length of postoperative ICU stay were longer,the hospitalization expense was higher,the 90-d fatality was higher,the albumin level at postoperative 14 d was lower,and total bilirubin level at postoperative 30 d was higher in the KP infection group.The differences were statistically significant(all P<0.05).Among 33 recipients with KP infection,16 cases were resistant to carbapenem antibiotics,and 7 of them died within postoperative 90 d.Seventeen cases were intermediate or sensitive to carbapenem antibiotics,and 4 of them died within postoperative 90 d.Preoperative MELD score ≥17 and operation time≥415 min were the independent risk factors for KP infection after liver transplantation(both P<0.05).The length of postoperative ICU stay ≥44 h and KP infection were the independent risk factors for long-term prognosis of liver transplantation(both P<0.05).Conclusions KP infection is an independent risk factor for death after liver transplantation.High preoperative MELD score and long operation time are the independent risk factors for early KP infection after liver transplantation.
5.Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation
Rong FU ; Ren LIN ; Zhiping FAN ; Fen HUANG ; Na XU ; Li XUAN ; Yifei HUANG ; Hui LIU ; Ke ZHAO ; Zhixiang WANG ; Ling JIANG ; Min DAI ; Jing SUN ; Qifa LIU
Chinese Journal of Hematology 2024;45(1):62-67
Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.
6.Effects and mechanism of insulin-like growth factor 1 on the secretion of transforming growth factor β2 and matrix metalloproteinase 2 in human reti-nal pigment epithelial cells
Rongrong CHAO ; Liu ZHENG ; Jing FAN ; Zhixiang DING
Recent Advances in Ophthalmology 2024;44(7):512-517
Objective To investigate the effects of insulin-like growth factor 1(IGF-1)on the expression of transfor-ming growth factor β2(TGF-β2)and matrix metalloproteinase 2(MMP-2)in human retinal pigment epithelial cells(ARPE-19)and related mechanisms.Methods ARPE-19 cells were cultured for 6 h,12 h,24 h and 48 h,respectively,with dif-ferent concentrations of IGF-1 and LY294002.The cell viability was detected using the cell counting kit-8 to determine the optimal action concentration and time of IGF-1 and LY294002.The cell migration activity was detected using the cell scratch assay.The concentration of TGF-β2 in cell culture supernatant was detected using the enzyme-linked immunosorbent assay(ELISA).ARPE-19 cells were divided into the control group,IGF-1 group(80 μg·L-1 IGF-1),IGF-1+LY294002 group(80 μg·L-1 IGF-1+30 mmol·L-1 LY294002),and LY294002 group(30 mmol·L-1 LY294002)and cultured with serum-free DMEM/F12 medium,while cells in the control group received no treatment.The mRNA and protein expression levels of TGF-β2,MMP-2,phosphoinositide 3-kinase(PI3K)and protein kinase B(AKT)in the cells were measured using the re-verse transcription-polymerase chain reaction(RT-PCR)and Western blot,respectively.Results Compared with the 0μg·L-1 IGF-1 group,the cell viability in the 80 μg·L-1 IGF-1 group changed the most significantly at 24 h(P<0.05);thus,the optimal concentration of IGF-1 was 80 μg·L-1 and the optimal culture time was 24 h.Compared with the 0 mmol·L-1 LY294002 group,the inhibition concentration in the 30 mmol·L-1 LY294002 group at 24 h was close to half;thus,the optimal concentration of LY294002 was 30 mmol·L-1 and the optimal culture time was 24 h.The cell scratch assay re-sults showed that the cell migration rate was significantly different among the 0 μg·L-1 IGF-1 group,40 μg·L-1 IGF-1 group,and 80 μg·L-1 IGF-1 group(all P<0.05).ELISA results showed that there was a statistically significant difference in the concentration of TGF-β2 in cell supernatant among the 0 μg·L-1 IGF-1 group,40 μg·L-1 IGF-1 group,and 80 μg·L-1 IGF-1 group(all P<0.05).RT-PCR and Western blot results showed that after 24 h culture with IGF-1 and LY294002,compared with the control group,the mRNA and protein expression levels of TGF-β2,MMP-2,PI3K and AKT in the IGF-1 group increased,while the mRNA and protein expression levels of TGF-β2,MMP-2,PI3K and AKT in the LY294002 group decreased(all P<0.05).Compared with the IGF-1 group,the mRNA and protein expression levels of TGF-[32,MMP-2,PI3K and AKT in the IGF-1+LY294002 group decreased(all P<0.05).Conclusion IGF-1 can promote the proliferation and migration of ARPE-19 cells.IGF-1 may up-regulate the expression of TGF-β2 and MMP-2 in ARPE-19 cells through the PI3K/AKT signaling pathway and participate in the occurrence and development of myopia.
7.Transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation for Budd-Chiari syndrome complicated with liver cancer: a case report with surgical video
Zhenghui YE ; Hongchuan ZHAO ; Xiaoping GENG ; Fan HUANG ; Guobin WANG ; Wei WANG ; Xiaojun YU ; Ruolin WU ; Liujin HOU ; Xinghua ZHANG ; Zhixiang HE
Organ Transplantation 2023;14(6):855-860
Objective To summarize clinical experience of transabdominal pericardial anastomosis of suprahepatic vena cava of the donor and right atrium of the recipient in liver transplantation for Budd-Chiari syndrome (BCS) complicated with liver cancer. Methods Clinical data of a BCS patient complicated with liver cancer undergoing transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation were retrospectively analyzed. Results The hepatic vein and suprahepatic vena cava were partially occluded in the patient. Liver transplantation was completed by transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium with beating-heart. In addition, due to pathological changes of the recipient's hepatic artery, splenic artery of the recipient was cut off, distal ligation was performed, and the proximal end was reversed and anastomosed with the common hepatic artery of the donor liver, and the reconstruction of hepatic artery was completed. The surgery was successfully performed. At approximately postoperative 1 week, the function of the liver allograft was gradually restored to normal, and no major complications occurred. The patient was discharged at postoperative 25 d. No signs of BCS recurrence was reported after 8-month follow-up. Conclusions It is safe and feasible to treat BCS by liver transplantation with transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium. BCS patients complicated with liver cancer obtain favorable prognosis.
8.Targeted therapy for small cell carcinoma of prostate: a case report
Chenfei CHI ; Jiazhou LIU ; Liancheng FAN ; Yongheng SHI ; Zhixiang XIN ; Jiahua PAN ; Jianjun SHA ; Yinjie ZHU ; Wei XUE ; Baijun DONG
Chinese Journal of Urology 2022;43(4):299-300
A patient aged 68 years old presented urinary frequency, urgency, and gross hematuria for 1 month, with initial PSA of 72.72 ng/ml and alkaline phosphatase (ALP)of 114 U/L. Prostate biopsy pathology showed small cell neuroendocrine carcinoma of prostate. The patient was immediately administered 6 cycle of chemotherapy including etoposide and cisplatin combined with medical castration. The CDK4 gene was detected 1.99 times amplification by peripheral blood free DNA (cfDNA)gene analysis. The chemotherapy was followed by parbosini therapy. The number and density of bone metastases continued to decrease significantly by bone scan at 3 and 6 months after treatment, with a continuous decline of ALP and PSA. After 1 year of follow-up, pelvic MRI and bone systemic imaging indicated stable lesions, with PSA of 0.05 ng/ml and ALP of 59 U/L.
9.Closed reduction and minimally invasive fixation for the treatment of pelvic fractures of type C2 and C3
Chengliang YANG ; Xiaodong YANG ; Jia LIU ; Yujin TANG ; Zhixiang LIU ; Qiguang MAI ; Tao LI ; Jianwen LIAO ; Shicai FAN
Chinese Journal of Orthopaedics 2021;41(19):1380-1386
Objective:To explore the surgical indications, techniques and methods of closed reduction and minimally invasive fixation for the treatment of pelvic fractures of Tile C2 and C3, and evaluate the clinical efficacy.Methods:A retrospective analysis of the data of 20 cases with Tile C2 and C3 pelvic fractures treated with closed reduction and minimally invasive fixation from January 2016 to July 2019. There were 7 males and 13 female, with an average age of 35.6±14.6 years (range 12-60 years). The time from injury to operation was 5-30 d, with an average of 19.3±7.1 d. Tile classification of pelvic fracture: 13 cases of C2 type and 7 cases of C3 Type. 2 cases were complicated with ipsilateral or bilateral lumbosacral nerve injury. Classification of nerve injury: 2 cases were partial injury, British Medical Research Council (BMRC) Grade M3. The operation is treated with closed reduction and minimally invasive fixation. First, the side with obvious displacement is fixed on the operating table with a pelvic reduction frame, and the side with less displacement is traction. After reduction, insert S 1 and S 2 sacroiliac screw guide-pin on this side to the contralateral sacral fracture. And then change the traction, fix the reset side on the operating table, change the side with obvious traction displacement, after the reset is ideal, pass the inserted guide-pin through the contralateral sacroiliac joint to the outer iliactable. Then insert the sacroiliac screw. The patients complicated with acetabular fracture were reduced and fixed by the corresponding approach, and the anterior ring was fixed by INFIX. The operation time, intraoperative bleeding volume and postoperative complications were recorded. The quality of fracture reduction was evaluated by Matta's criteria, and the clinical effect was evaluated by Majeed score. Results:All the 20 patients successfully completed the operation. The operation time was 105-210 min, with an average of 167.00±31.21 min. The intraoperative bleeding volume was 30-100 ml, with an average of 82.00±5.36 ml. Postoperative X-ray and CT showed that the fracture was reduced and fixed. According to the Matta's criteria, the reduction quality was rated as excellent in 14 cases, good in 4 case, fair in 2 case, with an excellent and good rate of 90%. Two patients showed symptoms of lateral femoral cutaneous nerve injury without other complications related to surgery. Follow-up for 1 to 4 years, the fractures healed, and the healing time was 6 to 12 weeks. According to the Majeed score, the result was rated as excellent in 18 cases, good in 2 case, with an excellent and good rate of 100%.Conclusion:Closed reduction and minimally invasive fixation for the treatment of pelvic fractures of type C2 and C3, with the characteristics of less damage and good results, will become a trend in the treatment of pelvic fractures.
10.Intensification of pegaspargase in pretransplant chemotherapy regimens reduced relapse of adult Philadelphia chromosome-negative acute lymphoblastic leukemia after transplantation
Zhixiang WANG ; Qiang WANG ; Ren LIN ; Xuan ZHOU ; Zhiping FAN ; Feng HUANG ; Na XU ; Pengcheng SHI ; Hongsheng ZHOU ; Qifa LIU
Chinese Journal of Organ Transplantation 2021;42(4):209-213
Objective:To explore risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-ALL).Methods:A retrospective analysis was performed for 65 adult Ph-ALL patients undergoing initial allo-HSCT from 2016 to 2018. The effect of baseline level and treatment pre-transplantation for relapse after allo-HSCT was analyzed.Results:There were 37 males and 28 females with a median age of 25(14-58) years during allo-HSCT. And the median follow-up period was 27 months post-HSCT. The 2-year overall survival (OS) was 78.8%(95%CI 67.8%-89.8%) and the 2-year relapse-free survival (RFS) 70.7% (95%CI 58.2%-83.2%). Pre-transplant chemotherapy was offered for 3 to 7 courses and the median dose of polyethylene glycol-conjugated asparaginase (PEG-ASP) was 3 doses (2 000 IU/m 2 per dose). Multiariate analysis revealed that the regimen included more than 4 doses of PEG-ASP pre-HSCT (HR=4.067, P=0.046) was a protective factor for post-transplant relapse (HR=0.193, P=0.009). High-risk chromosome karyotype was a risk factor for relapse (HR=0.193, P=0.009). The 2-year RFS rate was 90.0%(95%CI 79.2%-100.0%) for intensive PEG-ASP group and 56.9%(95%CI 39.1%-74.7%) for control group ( P=0.01). No significant inter-group difference existed in overall survival (OS)( P=0.079). The 2-year OS was 90.6% (95%CI 80.4%-100.0%) in intensive PEG-ASP group and 72.1% (95%CI 56.6%-87.6%) in control group. Conclusions:For adult ph-ALL patients, a higher dose of PEG-ASP in pretransplant chemotherapy regimens may improve post-transplant RFS and achieve a better outcome.

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