OBJECTIVETo establish a new rat model of chronic cyclosporine A nephrotoxicity and explore its features.

METHODSTotally 24 male SD rats were equally randomized divided into 3 groups: sham-adrenalectomized (sham-ADX) group, ADX group and ADX plus cyclosporine A (CsA) group. Rats in ADX and CsA group first underwent adrenalectomy, followed by the administration of placebo or dexamethasone, respectively. Rats in sham-ADX group received sham adrenalectomy and distilled water as control. Six weeks later, all rats were sacrificed and the following indicators were evaluated: urine protein excretion, creatinine clearance, aldosterone level in serum and urine, aldosterone level and its synthase CYP11B2 gene expression in kidney, serum natrium and potassium, urine natrium and potassium excretion, and tubulointerstitial fibrosis by masson trichrome stain.

RESULTSIn ADX and CsA group, serum and urine aldosterone were undetectable on the second post-operative day, with other observations including natriuresis, hyponatremia, decreased urine potassium excretion, and hyperpotassemia, suggesting that adrenals were removed intact and the adrenalectomy was successful. Rats in CsA group showed increased urine protein, decreased creatinine clearance and tubulointerstitial fibrosis, suggesting that a model of chronic CsA nephrotoxicity was successfully established. At the endpoint, serum potassium, serum aldosterone, urine potassium and urine aldosterone excretion partially retrieved. Natrium in serum and urine was not significant different between ADX group/CsA group and sham-ADX group. Local renal aldosterone and its gene expression were remarkably upregulated.

CONCLUSIONSWe successfully established a new rat model of chronic CsA nephrotoxicity by adrenalectomy without low sodium diet. After adrenalectomy, local renal aldosterone in kidney may compensate for circulatory aldosterone deficit to maintain electrolyte balance.

Acute Kidney Injury ; chemically induced ; Adrenalectomy ; Aldosterone ; metabolism ; Animals ; Cyclosporine ; toxicity ; Disease Models, Animal ; Immunosuppressive Agents ; toxicity ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

The present study is to elucidate the mechanisms underlying Gleevec-induced apoptosis of chronic myeloid leukemia (CML) K562 cells in vitro. The apoptotic cell death and cell cycle distribution after Gleevec treatment and the effect of PDCD4 siRNA on Gleevec-induced apoptosis of K562 cells were analyzed by flow cytometry. The effect of Gleevec on p-Crkl, caspase-3, PARP and PDCD4 protein levels, and the knockdown efficacy of PDCD4 siRNA were detected by Western blotting. The results showed that Gleevec dramatically suppressed the phosphorylation level of Crkl in a dose-dependent manner and induced significant apoptosis and G0/G1 cell cycle arrest of K562 cells in time- and dose-dependent manners. In addition, Gleevec activated caspase-3 and its downstream substrates PARP, and the caspase pan inhibitor Z-VAD-FMK (50 micromol x L(-1)) markedly reduced Gleevec-induced apoptosis from 47.97% +/- 10.56% to 31.05% +/- 9.206% (P < 0.05). Moreover, Gleevec significantly increased the protein expression of programmed cell death 4 (PDCD4). PDCD4 knockdown by siRNA reduced Gleevec-induced apoptosis from 46.97% +/- 14.32% to 42.8% +/- 11.43%. In summary, Gleevec induced apoptosis in K562 cells via caspase-3 activation.
Amino Acid Chloromethyl Ketones ; Apoptosis ; drug effects ; Benzamides ; pharmacology ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; Humans ; Imatinib Mesylate ; K562 Cells ; Phosphorylation ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Female ; Humans ; Neoplasm Metastasis ; Uterine Cervical Neoplasms ; pathology

OBJECTIVETo explore clinical effects of anterior cervical decompression and fusion by microscope in treating cervical spondylotic myelopathy.

METHODSFrom February 2005 to March 2010,21 patients with cervical spondylotic myelopathy, 13 males and 8 females with an average age of 51.5 years (ranged, 32 to 71), were treated with anterior cervical decompression using high-speed bur,then bone grafting and fusion with auto iliac bone and internal fixation by microscope. According to JOA score of cervical spondylosis to evaluate clinical effects before and after operation.

RESULTSAll patients were followed up from 18 to 24 months with an average of 20 months. JOA score improved significantly from preoperative 9.26 +/- 1.72 to postoperative 13.64 +/- 1.38 (t = 2.452, P = 0.000). According to JOA score, 12 cases were excellent, 7 good and 2 fair.

CONCLUSIONAnterior cervical decompression and fusion by microscope is a refined, safe and effective surgical procedure for cervical spondylotic myelopathy.

Adult ; Aged ; Cervical Vertebrae ; surgery ; Decompression, Surgical ; methods ; Female ; Humans ; Male ; Microscopy ; Middle Aged ; Spinal Fusion ; methods ; Spondylosis ; surgery

Objective To study the hotspots and trend in research of wearable device. Methods The research hotspots and trend of wearable device were analyzed by literature investigation and bibliometrics. Results The pros-pect of wearable device is broad in the coming years. The powerful electronic and technological nations such as USA and South Korea were the major original places of new technologies for wearable device. The core competitive-ness, complete industry chain, main manufacture system and application of wearable device in our country still had a long way to go compared with those in USA and South Korea. Co-word and clustering analysis showed that the current research hotspots of wearable device were its design concept, new sensor technology and energy store device technology. Literature investigation revealed that independence, low endurance high integration technology, human-computer interaction technology, big data and cloud technology were the main trend of future wearable device. Conclusion Wearable device is still in its initial stage with a lot of problems to be solved in its design, function and management. However, its development prospect is broad.

Objective To investigate the changes of cognitive impairment and its correlated factors in patients with first acute cerebral ischemic stroke.Methods Five hundred and sixty-eighty patients,admitted to our hospital from July 2010 to June 2011 and met the diagnostic criteria of first acute cerebral ischemic stroke,were chosen in our study; neuropsychological evaluation was conducted within 1 week of acute cerebral ischemic stroke.The comprehensive neuropsychological evaluation battery included mini-mental state examination (MMSE),Digit span,Mattis dementia scale,Rey complex figure test,stroop test,World Health Organization and University of California-Los Angeles auditory verbal learning test,semantic category verbal fluency test and clock drawing test,which contained tests for memory,attention,executive function,information processing capability,visuospatial and visuo constructive functions.Gender,age,histories of hypertension and smoking,and levels of blood pressure,random blood glucose,fasting blood glucose and 2-hour postprandial blood glucose,cholesterin,triglyceride,low density lipoprotein-C (LDL-C) and high density lipoprotein-C (HDL-C) were noted and the relations between cognitive function and both blood sugar and blood lipid levels were analyzed.Results (1) The abnormal rates of these patients in MMSE,Mattis dementia scale,attention deficit disorder,immediate logical memory disorder,delayed logical memory disorder,instant auditory memory disorder,delayed auditory memory disorder,visual memory disorder,executive function disorder,information processing disorder,and visuospatial and visuo constructive disorder were 78.2％,72.5％,26.5％,56.3％,60.9％,74.6％,98.2％,83.8％,62.7％,4.9％ and 77.7％,respectively.In patients with different blood glucose levels,significant differences were found on scores of MMSE,Mattis dementia scale,attention scale (P＜ 0.05); furthermore,the scores ofMMSE,Mattis dementia scale,attention scale in patients with impaired fasting glucose were obviously lower as compared with those in other groups (P＜0.05).The scale of above cognitive domains showed no significant difference in patients with different types of hyperlipidemias (P＞0.05); the scores of execution ability and visual space structure capability in patients with HDL-C were higher than those in normal density lipoprotein-C and LDL-C (P＜0.05),and the higher level of density lipoprotein-C,the higher scores of visual space structure capability (P＜0.05).Logistic regression analysis found that the total MMSE scores were associated with gender,age,and levels of fasting blood glucose and 2-hour postprandial blood glucose; the independent risk factors of executive function were gender,age and HDL-C level; the ability of memory was correlated with age and HDL-C level.Visuospatial and visuo constructive function was associated with gender,age and mRS scores; the information processing ability was only correlated with HDL-C level.Conclusion In patients with acute cerebral ischemic stroke,the cognitive impairment is extensive and severe,with a prevalence of about 75％,mainly having disorders in memory,executive ability,spatial structure; glucose levels,especially impaired fasting glucose level show most obvious influence in cognitive impairment;HDL-C level helps keep normal cognitive function; age,gender,HDL-C level are the most important factors of cognitive function.

OBJECTIVETo characterize the profile of chromosomal imbalances of rhabdomyosarcoma(RMS).

METHODSComparative genomic hybridization (CGH) was used to investigate genomic imbalances in 25 cases of primary RMS including 10 cases of alveolar rhabdomyosarcoma (ARM), 12 cases of embryonic rhabdomyosarcoma (ERMS), 3 cases of polymorphic rhabdomyosarcoma (PRMS) and 2 RMS cell lines (A240 originated from ARMS and RD from PRMS), with correlation to histological type, pathologic grading, clinical staging, gender and age, respectively.

RESULTSAll twenty-five rhabdomyosarcomas showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome regions in RMS were 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q, and the frequently lost chromosome regions were 3p, 11p, 6p. (2) The frequently gained chromosome arms in ARMS were 12q, 2p, 6, 2q, 4q, 10q, 15q. The frequently lost chromosome arms were 3p, 6p, 1q, 5q. The frequently gained chromosome regions in ERMS were 7p, 9q, 2p, 18q, 1p, 8q. The frequently lost chromosome arms in ERMS were 11p. (3) The frequently gained chromosome arms in translocation associated RMS were 12q, 2, 6, 10q, 4q and 15q (> 30%), 3p, 6p, 5q (> 30%) were the frequently loss chromosome arms. The frequently gained chromosome regions in non-translocation associated RMS were 2p, 9q, 18q (> 30%), and 11p, 14q (> 30%) were the frequently loss chromosome regions. Gain of 12q was significantly correlated with the translocation-associated tumors (P < 0.05). (4) Gains of 9q was significantly correlated with clinical staging (P < 0.05).

CONCLUSIONSGain of 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q and loss of 3p, 11p, 6p may be involved in the tumorigenesis of RMS. Gains of 12q may be correlated with gene fusion/chromosomal translocation in ARMS. Gains of 9q may be correlated with an early tumor stage of RMS.

Adolescent ; Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes ; Comparative Genomic Hybridization ; methods ; Female ; Gene Fusion ; Humans ; Infant ; Male ; Middle Aged ; Neoplasm Staging ; Rhabdomyosarcoma ; genetics ; Spectral Karyotyping ; methods ; Young Adult

BACKGROUNDOff-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.

METHODSThe FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.

RESULTSLong lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.

CONCLUSIONSThe results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use ; Treatment Outcome

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Community-Acquired Infections ; epidemiology ; microbiology ; Female ; Humans ; Male ; Middle Aged ; Pneumonia, Mycoplasma ; epidemiology ; Young Adult