1.Application of kidney sparing surgery based on Thulium laser ablation and systemic therapy in localized high-risk UTUC
Bo TANG ; Zeyu CHEN ; Xiang TU ; Xinyang LIAO ; Tianhai LIN ; Peng ZHANG ; Jiyan LIU ; Yali SHEN ; Hao ZENG ; Xiang LI ; Qiang WEI ; Yige BAO
Chinese Journal of Urology 2024;45(7):502-507
Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.
2.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
3.Changes and significance of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis
Xiaodong HUANG ; Jiyan LIN ; Penghui DU ; Xianwei HUANG ; Mandong PAN ; Qicong WANG ; Jianbao HUANG ; Qingliu ZHENG ; Qiqi WU ; Jun HU
Chinese Journal of Emergency Medicine 2022;31(1):92-97
Objective:To explore the characteristics of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis (HLAP) and its prognostic value.Methods:This study included 184 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2021. Based on disease etiology, there were 92 HLAP cases and 92 non-hyperlipidemia-induced AP (NHLAP) cases. Stratified by disease severity according to 2012 Atlanta classification criteria, the patients were divided into the severe subgroup (SAP) and non-severe subgroup (NSAP). Peripheral venous blood samples were taken from all patients on day 1, 3, and 5 after admission. T lymphocyte subsets were determined by flow cytometry, and cytokines were detected by flow fluorometry. The number of CD4 +% and CD8 +% and the expression of cytokines were compared by Student’s t test or Mann-Whitney U analysis. Logistic regression analyses were performed to identify risk factors for severe AP, and a receiver operating characteristic (ROC) curve was constructed to predict severe AP. Statistical significance was taken as P<0.05. Results:Compared with the NHLAP group, patients in the HLAP group had lower CD4 +%, while higher levels of IL-2 on day 1 ( P<0.05), and had also lower CD4 +%, while higher levels of IL-4, IL-6, and IL-10 on day 3 ( P<0.05). Furthermore, IL-6 and IL-10 levels of the HLAP group were significantly increased compared to the NHLAP group on day 5 ( P<0.05). IL-10 levels in the SAP subgroup were significantly higher than those in the NSAP subgroup on day 1 ( P<0.05). Compared with the NSAP subgroup, the SAP subgroup had elevated levels of IL-2, IL-4, IL-6, IL-10 and IFN-γ on day 3 (all P<0.05), and had lower CD4 +%, while increased levels of IL-6 and IL-10 on day 5 (all P<0.05). Multivariate Logistic regression analysis showed that IL-10 was an immune indicator of independent risk factor for severe AP in the HLAP group on day 1 ( OR=1.139, 95% CI: 1.038-1.251, P<0.05). Finally, ROC analysis showed that the area under the curve of IL-10 to assess HLAP with severe AP was 0.772, and the best cut-off value for predicting severe AP was 5.6 pg/mL, with a sensitivity of 83.3% and a specificity of 68.8%. Conclusions:Changes of CD4 +% and cytokines are different between the HLAP and NHLAP groups. IL-10 can be used as a predictor of early disease severity in patients with HLAP.
4.Establishment of early prediction model for patients with hyperlipidemic severe acute pancreatitis
Chengbin YANG ; Jiyan LIN ; Liren LAI ; Jianbao HUANG ; Qiqi WU ; Weicheng WU
Chinese Journal of Emergency Medicine 2021;30(7):856-861
Objective:To establish an early prediction model with multiple indicators to predict the risk of severe acute pancreatitis (SAP) in hyperlipidemic acute pancreatitis (HLAP).Methods:The clinical data of 92 patients with HLAP admitted to the Emergency Department of our hospital from March 2018 to February 2020 were analyzed retrospectively. Among them, 29 cases deteriorated to SAP and 63 cases did not. Univariate analysis was used to screen predictive indicators related to hyperlipidemic severe acute pancreatitis (HL-SAP), and logistic regression analysis was used to screen independent predictive indicators related to HL-SAP. Then a prediction model was established. The area under (AUC) the receiver operating curve (ROC) was used to evaluate the predictive ability of each predictive indicator and the model for HL-SAP. Bootstrap resampling technology was used to validate the predictive ability of the model.Results:Univariate analysis showed that procalcitonin, D-dimer, C-reactive protein, albumin, cholesterol and CT grade had influence on the progression of HLAP to SAP ( P<0.05). Logistic regression analysis showed that D-dimer ( OR=2.112, 95% CI: 1.022-4.366; P<0.05), CT grade ( OR=5.818, 95% CI: 2.481-13.643; P<0.01) and cholesterol ( OR=1.146, 95% CI: 1.004-1.308; P<0.05) were independent risk factor of HL-SAP. The AUC of D-dimer, CT grade, cholesterol and the model were 0.802, 0.875, 0.665 and 0.927, respectively. Internal validation of the predictive ability of the model showed that the C-index was 0.927. Conclusions:In the early phase, application of the prediction model that composes D-dimer, CT grade and cholesterol has a good predictive effect on HL-SAP.
5.Hydrogen can alleviate post-cardiac arrest myocardium injury in rabbits
Jingao WANG ; Jiyan LIN ; Minwei ZHANG ; Yujing HE ; Xiaowen PAN ; Chengbin YANG ; Dongmei CAI
Chinese Critical Care Medicine 2017;29(10):911-915
Objective To investigate the effects of hydrogen (H2) on myocardium injury post-cardiac arrest (CA) in rabbits.Methods Sixty New Zealand rabbits were randomly divided into H2 treatment group (n = 30) and control group (n = 30) by random number table. The rabbit CA model was established by means of electrical stimulation of external membrane, both groups were mechanically ventilated. Cardiopulmonary resuscitation (CPR) was performed after 6 minutes of nonintervention, and stopped after restoration of spontaneous circulation (ROSC). Inhalation of 2% H2 gas was conferred to rabbits immediately at the end of CA modeling for 72 hours in H2 treatment group. Air was given to rabbits in control group instead. The survival rate of rabbits was analyzed. Heart rate, ventricular premature beat frequency, and the levels of blood samples cardiac troponin I (cTnI), left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), and blood lactic acid (Lac) were collected before CA and after ROSC in all rabbits. Rabbits were sacrificed and microstructure injury was observed by electric microscope after ROSC 72 hours.Results There were 28 animals ROSC in both groups; the survival number in H2 treatment group was higher than that in control group at 72 hours after ROSC (number: 15 vs. 7,χ2 = 4.791,P = 0.029). In the early stage of ROSC, the heart rate of two groups slowed down, the number of premature ventricular increased, and then gradually recovered; the heart rate in H2 treatment group was returning to normal more quickly than that in control group at 48 hours after ROSC (bpm: 319±63 vs. 362±40,P < 0.05); the ventricular premature beat frequency was lower than that in control group at 72 hours after ROSC (times per minutes: 9.1±4.3 vs. 15.0±8.0,P < 0.05). The animals of two groups had different degrees of myocardial damage and cardiac insufficiency after ROSC, and restored with the extension of time. Compared with control group, the level of BNP in H2 treatment group was significant decreased at 24 hours after ROSC (ng/L: 385±98 vs. 488±174,P < 0.05), the levels of cTnI and Lac were significant decreased at 48 hours after ROSC [cTnI (μg/L:1.83±0.68 vs. 2.83±0.98, Lac (mmol/L): 5.5±1.6 vs. 7.9±2.6, bothP < 0.01], the LVEF was slightly higher than that at 72 hours after ROSC (0.690±0.040 vs. 0.650±0.041,P = 0.051). Compared with control group, less damage to myocardial ultra structure was found in H2 treatment group at 72 hours after ROSC.Conclusion Inhalation of H2 alleviates cardiac dysfunction and myocardial injury after CPR.
6.Application value of aortic dissection detection risk score in diagnosis of acute aortic syndromes: analysis of 342 patients with acute chest pain enclosed
Shuling LAI ; Jiyan LIN ; Jiaquan LIU ; Minwei ZHANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(5):473-476
Objective To investigate the value of aortic dissection detection (ADD) risk score in the diagnosis of acute aortic syndromes (AAS). Methods Three hundred and forty-two patients with acute chest pain or back pain admitted to the Department of Emergency of the First Affiliated Hospital of Xiamen University from January 2013 to April 2016 were enrolled. At last, 71 patients were definitely diagnosed as AAS (AAS group), and 271 cases were diagnosed as non-AAS (non-AAS group). Furthermore, according to the ADD risk score, they were subdivided into two groups: low-risk (ADD score ≤ 1) and high risk (ADD score >1) subgroups. In the two groups, the ADD risk indexes and the proportions of patients with different risk scores were observed; the receiver operating characteristic curve (ROC curve) was drawn to evaluate the value of ADD risk score for diagnosing AAS. Results Compared with the non-AAS group, the proportions of patients in AAS group with indicators of high-risk pain characteristics, such as sudden pain and laceration-like pain were increased significantly [83.1% (59/71) vs. 31.0% (84/271), 29.6% (21/71) vs. 0 (0/271)];meanwhile, the proportions of patients with high-risk physical examination indicators, such as systolic blood pressure differences among the 4 extremities and the defect of local nerve function in AAS group were also significantly increased [23.9% (17/71) vs. 0 (0/271), 11.3% (8/71) vs. 0 (0/271), both P < 0.05]; the proportion of patients with high risk AAS score in AAS group was higher than that in the non-AAS group [66.2% (47/71) vs. 1.5% (4/271), P < 0.01]. The sensitivity of ADD score ≥ 1 for diagnosis of AAS and area under ROC curve (AUC) were all higher than those of ADD score ≥2 (sensitivity: 98.6% vs. 66.2%, AUC: 0.819 vs. 0.564), moreover, the specificity and the positive predictive value of ADD score ≥ 2 for diagnosis of AAS were higher than those of ADD score ≥ 1 (98.5% vs. 59.8%, 92.2% vs. 39.1%respectively). When the ADD risk score ≥ 1, its odds ratio (OR) = 104.0, 95% confidence interval (CI) was 0.761-0.877, P = 0.000; while ADD risk score ≥ 2, OR = 130.7, 95%CI was 0.516-0.612, P = 0.003. Conclusion It is shown that when ADD risk score (> 1) is used to diagnose AAS, it has relatively high sensitivity, when ADD score being high risk (> 1 score) is applied to diagnose AAS, its specificity is high, thus ADD risk score has important value in helping the early diagnosis of AAS.
7.Association between apolipoprotein A1-75 bp gene polymorphisms and risk for dyslipidemia and coronary artery disease
Xuebiao WEI ; Yaowang LIN ; Xing YANG ; Dan LIAN ; Jiyan CHEN ; Danqing YU
Chinese Journal of Cardiology 2014;42(11):916-921
Objective To explore the relationship between the apolipoprotein ApoA1-75 bp polymorphism and risk for dyslipidemia and coronary artery disease (CAD).Methods A total of 723 patients (mean age (62.4 ± 10.2) years old) admitted to Guangdong General Hospital from 2011 to 2013 were enrolled.They were subdivided into CAD group (n =444) and non-CAD (n =279) group according to the result of coronary angiography (CAG).Clinical data including the profiles of lipids,-75 bp gene polymorphisms and Gensini scores were analyzed to determine the correlation between-75 bp gene polymorphisms,lipid profile and CAD.Result Frequency of male gender,history of diabetes and smoking,TC,TG,LDL-C and ApoB level were significantly higher and HDL-C level was significantly lower in CAD group than in non-CAD group (all P < 0.05).Frequency of A allele was significantly lower in CAD group than in non-CAD group (43.7% (194/444) vs.56.6% (158/279),P =0.003).The ApoA1-75 bp gene polymorphism was significantly correlated with CAD (P < 0.005).Multivariate logistic regression analysis showed that-75 bp gene polymorphism mutation (OR =0.649,P =0.021) is an independent protective factor for coronary heart disease.Conclusion ApoA1-75 bp gene polymorphism is linked with risk of dyslipidemia and CAD.
8.Comparison of the screening effects between Wells and revised Geneva scores on suspected acute pulmonary thromboembolism
Weicheng WU ; Jiyan LIN ; Chengbin YANG ; Yuzhen WU ; Xiangmei YU ; Jiaquan LIU ; Zili ZHANG
Chinese Journal of Emergency Medicine 2012;21(3):282-285
Objective To compare the screening effects between Wells and revised Geneva scores on suspected acute pulmonary thromboembolism (APTE),and to explore a optimum screening method for APTE in the emergency department of China.Methods The study was carried out by using random,crossed,prospective methods to compare the screening effects between Wells and revised Geneva scores for 167 suspected APTE patients in the emergency department of the First Affiliated Hospital of Xiamen University.Results The areas under the receiver operating characteristic curve of Wells and revised Geneva scores for screening APTE in the emergency department were (0.917 ± 0.022 ) and (0.927 ± 0.020),respectively ( P < 0.05 ).The diagnostic concordance between the two score systems for predicting APTE was poor (Kappa value =0.276 ). In addition, the difference between their hierarchical discrimination for the possibility of APTE was statistically significant ( P < 0.05 ).Compared with revised Geneva score,fewer patients were diagnosed with low clinical probability of APTE and more patients were diagnosed with intermediate or high clinical probability of APTE through Wells score.The patients with low chnical probability of APTE were excluded from pulmonary embolism in Wells or revised Geneva score.At intermediate clinical probability,the accuracy rate of Wells score for predicting APTE (9.64%) was lower than that (32.84% ) of revised Geneva ( P < 0.05 ).At high clinical probability,there was no significant difference between their accuracy rate [ (67.24% vs.86.21%),P>0.05]. Conclusions Revised Geneva score is more suitable than Wells score in screening suspected APTE patients in the emergency department in our country.
9.Screening effects of Montreal Cognitive Assessment for sepsis associated encephalopathy
Jiaquan LIU ; Zili ZHANG ; Dequan KONG ; Chengbin YANG ; Yuzhen WU ; Yaben YAO ; Weicheng WU ; Mandong PAN ; Jiyan LIN
Chinese Journal of General Practitioners 2012;11(9):680-682
A total of 192 patients with sepsis were tested by Montreal Cognitive Assessment (MoCA) for a preliminary diagnosis of whether or not there was sepsis associated encephalopathy (SAE) according to their test results.SAE was diagnosed or excluded after consultations and comprehensive analysis on the basis of clinical manifestations and auxiliary examination results.The scores of the patients in this group were (25.7 ± 3.3) points.The sensitivity of MoCA for screening SAE was 0.776 and its specificity 0.963.The rate of diagnostic coincidence between MoCA and comprehensive analysis for SAE was 0.880.The diagnostic concordance between two diagnostic methods of SAE was excellent (kappa value =0.753 ± 0.048,P =0.000).The area under the receiver operating characteristic (ROC) curve of MoCA for screening SAE was 0.929 ± 0.019 (P =0.000) ; the optimal cutoff value was 25.5 points; and its sensitivity was 0.779 and specificity 0.962.And negative correlations existed between score of MoCA and age,disease course and co-existing shock or multiple organ dysfunction syndrome (P < 0.05).
10.Hydrogen can alleviate post-cardiac arrest brain injury in rabbits
Jingao WANG ; Jiyan LIN ; Dequan KONG ; Zili ZHANG ; Xiangmei YU ; Jiaquan LIU ; Dongmei CAI
Chinese Journal of Emergency Medicine 2012;21(10):1111-1115
Objective To investigate the effects of hydrogen on post - cardiac arrest brain injury in rabbits.Method Sixty New Zealand rabbits were randomly divided into two groups,namely experiment group ( group A,n =30 ) and control group ( group B,n =30 ).Inhalation of 2% hydrogen gas was conferred to rabbits immediately at the end of cardiac arrest modeling for 72 hours in the group A. Air instead was given to rabbits in the group B.Blood samples were collected before cardiac arrest (CA),and 4,12,24 and 72 hours after restoration of spontaneous circulation (ROSC) in all rabbits for determining the levels of hydrogen,tumor necrosis factor - α ( TNF - α),neuron - specific enolase (NSE) and protein S100β.At the same time,rectal temperature,mean arterial pressure,heart rate and respiration rate were recorded,and the neurologic deficit scoring (NDS) was carried out.The rate of systemic inflammatory response syndrome ( SIRS ) and the rate of survival of rabbits were analyzed. Results There was no significant difference in level of TNF - α activation between group A and group B within12 h of cardiopulmonary resuscitation (CPR).In group A,TNF - α level and the rate of SIRS peaked at 24 hours after CPR,which were higher than those in group B,and then decreased gradually,and the rate of survival was higher than that in group B in 72 hours after ROSC,the NSE was lower than that in group B at 24 hours after ROSC.In group B,S100β level began to increase significantly 4 hours after CPR,which was higher than that in group A,the level of NDS in group B was higher than that in group A 72 hours after ROSC.Conclusions Inhalation of hydrogen gas lessened inflammation and alleviated the brain injury after CPR.

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