1.GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer.
Qiwei JIANG ; Yong LI ; Songwang CAI ; Xingyuan SHI ; Yang YANG ; Zihao XING ; Zhenjie HE ; Shengte WANG ; Yubin SU ; Meiwan CHEN ; Zhesheng CHEN ; Zhi SHI
Acta Pharmaceutica Sinica B 2024;14(2):698-711
Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.
2.Application of virtual surgery combined with three-dimensional guide plate in the surgery of mandibular benign tumors resection and bone defect repairation
Kun FU ; Ning GAO ; Leilei YANG ; Kangyan LIU ; Jinghua CAI ; Zhenjie GAO ; Hao CHEN ; Bin ZHAO ; Wei HE
Chinese Journal of Plastic Surgery 2024;40(3):258-263
Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.
3.Application of virtual surgery combined with three-dimensional guide plate in the surgery of mandibular benign tumors resection and bone defect repairation
Kun FU ; Ning GAO ; Leilei YANG ; Kangyan LIU ; Jinghua CAI ; Zhenjie GAO ; Hao CHEN ; Bin ZHAO ; Wei HE
Chinese Journal of Plastic Surgery 2024;40(3):258-263
Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.
4.Pure white cell aplasia combined with thymoma and lung cancer: a case report and literature review
Xiuli CHEN ; Zhenjie CAI ; Rong ZHENG ; Wuqiang LIN
Chinese Journal of Hematology 2024;45(8):789-793
Pure white cell aplasia (PWCA) is a rare hematologic disorder. In this case study, a 67-year-old man presented with severe neutropenia along with thymoma and lung cancer. A comprehensive diagnostic approach was done which included routine blood test, bone marrow cytology, bone marrow pathology, flow cytometry, and thymic pathology. Other potential causes, such as pure red blood cell aplasia and myelodysplastic syndrome, were ruled out. The final diagnosis was determined to be thymoma-related PWCA. Continuous treatment with human granulocyte colony-stimulating factor (G-CSF) was ineffective for treating PWCA in this patient. The patient's white blood cell and neutrophil count increased following treatment with cyclosporine and subsequently returned to normal levels by the 8th day after thymectomy. A recurrence of PWCA was identified 40 days after the operation and coincided with COVID-19 infection. The patient eventually succumbed to a severe infection. Therefore, in cases of severe neutropenia with an unclear etiology, prompt evaluation of mediastinal and bone marrow status is imperative.
5.Regulating mechanism of dynein heavy chain on autophagic degradation of α-synuclein in Parkinson disease model cells
Jing LU ; Bo SUN ; Shikun CAI ; Xiangyang TIAN ; Quan CHEN ; Bin QI ; Lei WANG ; Xiangyuan CHEN ; Zhenjie SUN
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(10):871-878
Objective:To explore the regulatory mechanism of α-synuclein in the degradation of autophagy-lysosome pathway(ALP) in Parkinson disease(PD) model cells after interference or overexpression of dynein heavy chain(Dynhc) gene.Methods:SH-SY5Y cells were divided into control group, PD group, Dynhc interference group, Dynhc overexpression group, and Dynhc interference+ rapamycin group according to experimental requirements.Using Western blot to detect Dynhc, α-synuclein, microtubule-associated protein l light chain 3 (LC3), lysosome-associated membrane protein 2 (LAMP2), tubulin, dynein activator protein p150, and kinesin KIF5B.Flow cytometry was used to detect the level of cell apoptosis.Immunoconfocal microscopy was used to observe the structure of tubulin and the co-localization of LC3 and LAMP.SPSS 23.0 software was used for statistical analysis.One-way ANOVA was used for inter group comparisons, and further pairwise comparisons were conducted by LSD- t test. Results:There were statistically significant differences in the expression of α-synuclein, autophagy-related proteins, microtubules, and microtubule-related proteins among cells in the 5 groups(all P<0.001). The protein expression levels of Dynhc, α-synuclein, LC3, LAMP2, p150, and KIF5B in the PD group were higher than those in the control group (all P<0.05). The protein levels of Dynhc, LAMP2, tubulin and p150 in the Dynhc interference group were lower than those in the PD group (all P<0.05), while the protein levels of α-synuclein, LC3 and KIF5B were higher than those in the PD group (all P<0.05). The protein levels of α-synuclein, LC3, and KIF5B in the Dynhc overexpression group were lower than those in the PD group (all P<0.05), while the protein levels of Dynhc, LAMP2 and p150 were higher than those in the PD group (all P<0.05). The protein level of LC3 in the Dynhc interference+ rapamycin group was higher than that in the Dynhc interference group ( P<0.05). There were no statistically significant differences in the protein levels of Dynhc, α-synuclein, LAMP2, microtubule protein, p150 and KIF5B compared to the Dynhc interference group (all P>0.05). Compared with the control group, the cell apoptosis rate in PD group increased((12.77±1.66)%, (7.64±1.45)%), the microtubule morphology remained unchanged, and autophagosomes fused more with lysosomes. Compared with the PD group, the cell apoptosis rate of Dynhc overexpression group decreased, and there was no significant change in microtubule structure, and there was more fusion between autophagosomes and lysosomes.Compared with the PD group, the cell apoptosis rat of Dynhc interference group increased((18.45±1.91)%), and the microtubule morphology was sparse, and there was less fusion between autophagosomes and lysosomes. Compared with the PD group, the Dynhc overexpression group showed a decrease in cell apoptosis rate ((9.95±1.56)%), no significant changes in microtubule structure, and more fusion between autophagosomes and lysosomes.Compared with the Dynhc interference group, the Dynhc interference+ rapamycin group showed no significant changes in cell apoptosis rate ((19.05±2.46)%), microtubule morphology, and fusion of autophagosomes and lysosomes. Conclusion:Dynhc can reduce cell apoptosis by enhancing cell ALP function, increasing the degradation of α-synuclein and maintaining of microtubule structure integrity.
6.The preliminary application of extraperitoneal robot-assisted single-port laparoscopic radical prostatectomy
Guanqun JU ; Zhijun WANG ; Jiazi SHI ; Zhiping CAI ; Zongqin ZHANG ; Zhenjie WU ; Bing LIU ; Linhui WANG ; Dongliang XU
Chinese Journal of Urology 2021;42(1):61-62
There are few reports on the study of extraperitoneal robotic single-port laparoscopic radical prostatectomy in China. In this study, patients with localized prostate cancer were treated with extraperitoneal robotic single-port laparoscopic radical prostatectomy extraperitoneal robot-assisted single-port laparoscopic radical prostatectomy(EpRA-spRP)from April 2019 to June 2019.All patients performed EpRA-spRP successfully without adding additional auxiliary port. The operation time and blood loss were controllable, and hospitalization time was short. It is safe and feasible to perform EpRA-spRP for medium and low-risk prostate cancer. The short-term tumor control and functional recovery are satisfactory.However, the long-term effect needs further follow-up and observation.
7.Correlation of short-term blood pressure variability and outcome after intravenous thrombolysis in patients with acute ischemic stroke: a Meta-analysis
Jingfeng MING ; Xiangyu WANG ; Shuangshuang DONG ; Zhenjie SUN ; Yongjin ZHANG ; Min WANG ; Zhengxin SONG ; Zenglin CAI
International Journal of Cerebrovascular Diseases 2018;26(1):1-8
Objective To evaluate the relationship between short-term blood pressure variability and poor outcome and hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.Methods The Databases such as Wanfang,CNKI,Cochrane,Pubmed,EMBASE,and Web of Science were retrieved.The randomized controlled trials,cohort studies and case-control studies about blood pressure monitoring after intravenous thrombolytic therapy in patients with acute ischemic stroke and calculation and analysis of blood pressure variability were enrolled.The deadline for retrieval was December 2017.STATA 13.0 software was used to conduct Meta-analysis.Results A total of 9 non-randomized controlled trials with 19 161 patients were included.Four of them were prospective studies and 5 were retrospective studies.The relationship between short-term blood pressure variability and poor outcome (defined as a modified Rankin scale score >2) were investigated in 8 studies (a total of 19 045 patients).The relationship between short-term blood pressure variability and hemorrhagic transformation were investigated in 6 studies (with 18 456 patients).The results of Meta-analysis showed that short-term systolic blood pressure variability (every 10 mmHg change;1 mmHg =0.133 kPa) and poor outcome (odds ratio [OR] 1.55,95% confidence interval [CI] 1.22-1.86;P >0.001),hemorrhagic transformation (OR 2.39,95% CI 1.71-3.35;P =0.025),and symptomatic intracranial hemorrhage (OR 2.49,95% CI 1.39-4.39;P =0.048) had significant correlations.Conclusion The increased short-term blood pressure variability after intravenous thrombolysis in patients with acute ischemic stroke is associated with poor outcome,hemorrhagic transformation,and symptomatic intracranial hemorrhage.
8.Technical specification for clinical application of critical ultrasonography
Wanhong YIN ; Xiaoting WANG ; Dawei LIU ; Yangong CHAO ; Xiangdong GUAN ; Yan KANG ; Jing YAN ; Xiaochun MA ; Yaoqing TANG ; Zhenjie HU ; Kaijiang YU ; Dechang CHEN ; Yuhang AI ; Lina ZHANG ; Hongmin ZHANG ; Jun WU ; Lixia LIU ; Ran ZHU ; Wei HE ; Qing ZHANG ; Xin DING ; Li LI ; Yi LI ; Haitao LIU ; Qinbing ZENG ; Xiang SI ; Huan CHEN ; Junwei ZHANG ; Qianghong XU ; Wenjin CHEN ; Xiukai CHEN ; Daozheng HUANG ; Shuhan CAI ; Xiuling SHANG ; Jian GUAN ; Juan DU ; Li ZHAO ; Minjia WANG ; Song CUI ; Xiaomeng WANG ; Ran ZHOU ; Xueying ZENG ; Yiping WANG ; Liwen LYU ; Weihua ZHU ; Ying ZHU ; Jun DUAN ; Jing YANG ; Hao YANG ; Chinese Critical Ultrasound Study Group ; Gritical Hemodynamic Therapy Collabration Group
Chinese Journal of Internal Medicine 2018;57(6):397-417
Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.
9.Efficiency of glucocorticoid treatment in IgA nephropathy with massive proteinuria
Zhenjie CHEN ; Hang LI ; Jianfang CAI ; Yubing WEN ; Chao LI ; Peimei ZOU ; Xin ZHANG ; Mingxi LI ; Limeng CHEN ; Xuemei LI ; Xuewang LI
Chinese Journal of Nephrology 2017;33(8):561-566
Objective To investigate the clinicopathological characteristics of IgAN patients with massive proteinuria,as well as their treatment response to glucocorticoids and long-term prognosis.Methods Clinical and pathological parameters were collected in patients diagnosed with IgA nephropathy in our hospital from Jan 2003 to Oct 2015.Patients were followed up for at least six months under the treatment with full dosage of glucocorticoids.Responses of patients with and without nephrotic syndrome were compared.Results A total of 156 patients were enrolled for the analysis (86 patients in the nephropathic proteinuria group,and 70 patients in the nephrotic syndrome group).Patients presented with nephrotic syndrome showed higher proportion of IgM deposition in renal slides.There exited no difference in treatment response to glucocorticoids between the two groups.Patients with full or partial remission showed a better prognosis by Kaplan-Meier analysis than no remission group (P < 0.001).The ratio of segmental sclerosis was negatively correlated with treatment response to glucocorticoids by multiple linear regression (3 value=-0.330,P < 0.001).Multivariate Cox regression model showed that glomerular density (HR=0.45,P=0.02) and eGFR (HR=0.95,P=0.001)were independent influential factors for renal survival.Conclusions Patients presented with nephrotic syndrome show higher proportion of IgM deposition in renal slides.Patients in remission after treatment with 6-month glucocorticoids present a better prognosis than no remission patients,and glomerular density as well as eGFR are independent influential factors for renal survival.
10.Clinical analysis of intestinal infection in patients with acute leukemia after chemotherapy
Wuqiang LIN ; Zhenjie CAI ; Beibei ZHANG ; Linjun XIE ; Heyong ZHENG
Journal of Leukemia & Lymphoma 2017;26(8):478-482
Objective To analyze the clinical features of intestinal infection in patients with acute leukemia (AL) after chemotherapy. Methods The data of 103 cases of AL patients after chemotherapy from January 2014 to April 2016 were retrospectively analyzed, and categorical variables were compared by using chi-square test. Results A total of 364 cycles of chemotherapy was conducted among 103 patients, of which 66 times (18.13 %) in 59 cycles occurred intestinal infections, including twice intestinal infections in one cycle of chemotherapy in 7 cases. The incidence of intestinal infection was 27.48%(36/131) in group without complete remission (CR), and 9.87%(23/233) in CR group. There was a statistical difference between the two groups (P<0.01). Repeated intestinal infections were found in 46.67%of the patients who accepted multiple cycles of chemotherapy. In the same cycle of chemotherapy, the probability of recurrence of intestinal infection after chemotherapy was 3.7 times than patients without intestinal infection occurred during chemotherapy. The incidence of intestinal infection of patients with acute lymphoblastic leukemia (ALL) after primary inducing chemotherapy was higher than that of patients with acute myelogenous leukemia (AML) (P= 0.019). The incidence of intestinal infection combined with neutropenic was 9.89 % (36/364), and the incidence of intestinal infection was 8.24 % (30/364) in neutrophils > 0.5 × 109/L. There was no significant difference (P> 0.05). After chemotherapy, some patients with intestinal infection occurred acute abdomen, with high mortality rate. Conclusions Intestinal infection may occur in the procession of chemotherapy and myelosuppression. Special attention should be paid on intestinal infection, including reduction of blood stream infection and risk factors, as well as timely intervention.

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