1.Expression of Fas ligand mRNA in colon cancer and its clinical significance
Erxun DING ; Qiang WANG ; Kewen YUAN
Chinese Journal of General Surgery 2001;0(10):-
Objective To investigate the relationship between the expression of Fas ligand mRNA and the biological behavior and prognosis of colon cancer.Methods The expression of Fas ligand mRNA was examined in 52 cases of colon cancer by in situ hybridization (ISH) technique.Results Fas ligand mRNA expression was found in 30 out of 52 cases of colon cancer (58%). Fas ligand mRNA expression was positive in cancer tissues in 3 out of 12 cases (25%) with pericancer inflammation and in 27 out of 40 cases (68%) with no pericancer inflammation ( P
2.Diffusion-weighted b0 imaging diagnosis of acute intracerebral hemorrhage with 3.0T MR
Fei YUAN ; Yinshe LIU ; Kewen AI ; Jun ZHAO ; Bin YUAN ; Zhongqiang ZHANG
Chinese Journal of Medical Imaging Technology 2010;26(2):254-257
Objective To investigate the value of diffusion weighted imaging (DWI) in detecting acute intracerebral hemorrhage with 3.0T MR. Methods A total of 105 patients with acute strokes underwent MR examination within 3 days after on set. The detectability and reliability of intracerebral hemorrhage with the DWI b0 sequence was assessed. The results were compared with the gradient-echo (GRE) sequence. The results of the GRE sequence were used as the standard. Results DWI b0 images of 47 cases displayed clearly in 48 acute intracerebral hemorrhage patients. For the detection of acute intracerebral hemorrhage, DWI b0 images had a sensitivity of 97.92%, specificity of 100%, the positive predictive value of 100%, and the negative predictive value of 98.25%. Deoxyhemoglobin-induced hypointense rim was characteristic on DWI b0 images, the next was GRE. Conclusion In the setting of acute stroke, DWI can clearly distinct intracerebral hemorrhage and non-intracerebral hemorrhage with 3.0T MR scanner. With a more rapid and accurate MRI strategy to evaluate acute stroke including DWI, T1WI and T2WI sequences without GRE is helpful in clinical decision making.
3.Treatment strategies and therapeutic effects in treatment of floating knee in children
Quanwen YUAN ; Xiaodong WANG ; Yunfang ZHEN ; Zhixiong GUO ; Jin DAI ; Kewen WANG ; Chunhua YIN
Chinese Journal of Trauma 2017;33(6):527-531
Objective To investigate the treatment strategies and clinical effects in treatment of floating knee in children.Methods A retrospective case series study was made on 26 cases of floating knee treated from July 2005 to June 2015.There were 22 males and four females, aged from 2-14 years (mean, 7.6 years).According to the Letts classification of the floating knee, ten cases were with type A, four with type B, two with type C, eight with type D, and two with type E.Closed fractures were noted in 16 cases and open fractures in 10 cases.According to the Gustilo classification of open fractures, one was with type ⅢA, six with type ⅢB, and three with type ⅢC.One case was amputated from the distal of the femur, eight cases were treated by traction and plaster caster, and 17 cases were treated by reduction and fixation of both femoral and tibil fractures.Wound healing, fracture union, Karsstrom criteria for functional outcome and complications were detected.Results All patients were followed up for mean 2.8 years (range, 1-6 years).One case of Gustilo type ⅢA and six cases of Gustilo type ⅢB open fractures had wound healing after one-stage debridement.Two cases of Gustilo type ⅢC showed wound healing after second-stage skin grafting.One case of Gustilo type ⅢC had amputation wound infection and was cured after a second debridement and dress change.Two had delayed union and there was no nonunion.According to the Karlstrom criteria, the excellent and good rate of functional outcome was 25% and 83% respectively in nonoperative and operative population (P<0.05).Malunion was found in four cases, genu vagum in three and overgrowth of 10-20 mm in seven.There was no premature closure of epiphysis.Conclusion Femur and tibia immobilization of floating knee in children is effective for bone union and functional recovery.
4.Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer.
Juanjuan FENG ; Zhengke LIAN ; Xinting XIA ; Yue LU ; Kewen HU ; Yunpeng ZHANG ; Yanan LIU ; Longmiao HU ; Kun YUAN ; Zhenliang SUN ; Xiufeng PANG
Acta Pharmaceutica Sinica B 2023;13(3):1145-1163
MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.
5.Clinic-pathological characteristics of rare tubulointerstitial diseases.
Kewen SHI ; Shuguang YUAN ; Yao HUANG ; Zheng LI ; Chang WANG ; Hong LIU ; Lin SUN ; Fuyou LIU ; Xuejing ZHU
Journal of Central South University(Medical Sciences) 2022;47(10):1365-1374
OBJECTIVES:
Tubulointerstitial diseases is one of the common causes of renal dysfunction. Some rare pathological types are easy to be misdiagnosed and missedly diagnosed because of their low prevalence and relatively insufficient understanding, which affects the treatment and prognosis of patients. This study aims to explore clinical manifestations and pathological characteristics of several rare tubulointerstitial diseases, and therefore to improve their diagnosis and treatment.
METHODS:
A total of 9 363 patients diagnosed by renal biopsy in the Department of Nephrology, Second Xiangya Hospital, Central South University from November 2011 to September 2021 were selected. Six cases of light chain cast nephropathy (LCCN), 2 cases of light chain proximal tubulopathy (LCPT), 1 case of LCCN with LCPT, 4 cases of genetic tubulointerstitial disease, and 6 cases of non-genetic related tubulointerstitial lesion were screened out, and their clinical manifestations and renal biopsy pathological results were collected, compared, and analyzed.
RESULTS:
Patients with LCCN presented with mild to moderate anemia, microscopic hematuria, and mild to moderate proteinuria. Compared with patients with LCPT, proteinuria and anemia were more prominent in patients with LCCN. Five patients with LCCN and 2 patients with LCPT had elevated serum free kappa light chain. Five patients with LCCN presented clinically with acute kidney injury (AKI). Two patients with LCPT and 1 patient with LCCN and LCPT showed CKD combined with AKI, and 1 LCPT patient presented with typical Fanconi syndrome (FS). Five patients with LCCN, 2 patients with LCPT, and 1 patient with LCCN and LCPT were diagnosed with multiple myeloma. Five patients with LCCN had kappa light chain restriction in tubules on immunofluorescence and a "fractured" protein casts with pale periodic acid-Schiff (PAS) staining on light microscopy. Immunohistochemical staining of 2 LCPT patients showed strongly positive kappa light chain staining in the proximal tubular epithelial cells. And monoclonal light chain crystals in crystalline LCPT and abnormal lysosomes and different morphological inclusion bodies in noncrystalline LCPT were observed under the electron microscope. Six patients with LCCN were mainly treated by chemotherapy. Renal function was deteriorated in 1 patient, was stable in 4 patients, and was improved in 1 patient. Two patients with LCPT improved their renal function after chemotherapy. Four patients with genetic tubulointerstitial disease were clinically presented as CKD, mostly mild proteinuria, with or without microscopic hematuria, and also presented with hyperuricemia, urine glucose under normal blood glucose, anemia, polycystic kidneys. Only 1 case had a clear family history, and the diagnosis was mainly based on renal pathological characteristics and genetic testing. Compared with patients with non-genetic related tubulointerstitial lesion, patients with genetic tubulointerstitial disease had an earlier age of onset, higher blood uric acid, lower Hb and estiated glomemlar fitration (eGFR), and less edema and hypertension. Renal pathology of genetic tubulointerstitial disease presented tubular atrophy and interstitial fibrosis, abnormal tubular dilation, glomerular capsuledilation, and glomerular capillary loop shrinkage. Glomerular dysplasia and varying degrees of glomerular sclerosis were observed. Genetic tubulointerstitial disease patients were mainly treated with enteral dialysis, hypouricemic and hypoglycemic treatment. Two genetic tubulointerstitial disease patients had significantly deteriorated renal function, and 2 patients had stable renal function.
CONCLUSIONS
Patients with AKI or FS, who present serum immunofixation electrophoresis and/or serum free kappa light chain abnormalities, should be alert to LCCN or LCPT. Renal biopsy is a critical detection for diagnosis of LCCN and LCPT. Chemotherapy and stem cell transplantation could delay progression of renal function in patients with LCCN and LCPT. If the non-atrophic area of the renal interstitium presents glomerular capsule dilatation, glomerular capillary loop shrinkage, and abnormal tubular dilatation under the light microscopy, genetic tubulointerstitial disease might be considered, which should be traced to family history and can be diagnosed by genetic testing.
Humans
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Hematuria
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Immunoglobulin Light Chains/analysis*
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Multiple Myeloma
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Proteinuria
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Nephritis, Interstitial
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Acute Kidney Injury
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Anemia
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Renal Insufficiency, Chronic