BACKGROUNDIt is well documented that sevoflurane postconditioning (SP) has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 (Drp1).

METHODSA Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows: CON group, ischemia reperfusion (I/R) group, SP group , SP+proto-oncogene serine/threonine-protein kinase 1 (Pim-1) inhibitor II group, SP+dimethylsufoxide group, and Pim-1 inhibitor II group (n = 12, each). Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial I/R injury. The expressions of Pim-1, B-cell leukemia/lymphoma 2 (Bcl-2) and cytochrome C (Cyt C) in cytoplasm and mitochondria, the Drp1 in mitochondria, and the total Drp1 and p-Drp1ser637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016.

RESULTSSP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size (24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P< 0.05). However, Pim-1 inhibitor II significantly (P < 0.05) abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drp1ser637 in Sev group (P < 0.05) were upregulated. Meanwhile, SP inhibited Drp1 compartmentalization to the mitochondria followed by a reduction in the release of Cyt C. Pretreatment with Pim-1 inhibitor II significantly (P < 0.05) abolished SP-induced Pim-1/p-Drp1ser637 signaling activation.

CONCLUSIONSThese findings suggested that SP could attenuate myocardial ischemia-reperfusion injury by increasing the expression of the Pim-1 kinase. Upregulation of Pim-1 might phosphorylate Drp1 and prevent extensive mitochondrial fission through Drp1 cytosolic sequestration.

Animals ; Dynamins ; metabolism ; Hemodynamics ; drug effects ; Ischemic Postconditioning ; methods ; Male ; Methyl Ethers ; therapeutic use ; Mitochondria ; drug effects ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-pim-1 ; antagonists & inhibitors ; metabolism ; Quinazolinones ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the prognostic value of interimF-FDG PET/CT (i-PET/CT) scan for the patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

METHODSA total of 70 cases of initially diagnosed of DLBCL by 158F-FDG PET/CT scans in our hospital were retrospectively analyzed. The 5-point scale, the Lugano classification and maximum standardized uptake value induction (ΔSUVmax) criteria were used respectively to assess i-PET/CT scans. Receiver-operating characteristics (ROC) analysis was used to determine an optimal cutoff for ΔSUVmax. Progression-free survival (PFS) and overall survival (OS) times were estimated as prognostic indicators using the Kaplan-Meier method and Cox regression.

RESULTSOptimal cutoff to predict progression or death was 62% for ΔSUVmax. The positive predictive value (PPV) for 2-year PFS and OS of i-PET/CT diagnosed by 5-point scale was low, and could be improved by using the Lugano classification with decreased sensitivity or ΔSUVmax criteria. Kaplan-Meier survival curve analysis showed that the Lugano classification and ΔSUVmax were good predictors for PFS and OS, respectively, while the 5-point scale could only predict OS. Cox regression univariate analysis showed that the International Prognostic Index (IPI) score was better to predict PFS than 5-point scale, but worse than the three assessments in predicting OS. COX regression multivariate analysis showed that ΔSUVmax<62% was an independent risk factor of prognosis, while the Lugano classification was only the OS independent prognostic predictor.

CONCLUSIONAssessing i-PET/CT by 5-point scale is a limited value for predicting PFS and OS in DLBCL patients. The Lugano classification is recommended to discriminate the patients with poorer outcomes. The ΔSUVmax criteria for i-PET/CT of DLBCL patients is an independent prognostic predictor for PFS and OS, better than the IPI score.

OBJECTIVETo detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI).

METHODSClinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced.

RESULTSThe patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c.295 T>C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation.

CONCLUSIONThe congenital NDI in the patient was probably due to mutation of the AVPR2 gene.

Adolescent ; Base Sequence ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic ; congenital ; genetics ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Vasopressin ; genetics

In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.
Animals ; Evidence-Based Practice ; Genetic Engineering ; Genetic Therapy ; Hearing Loss, Sensorineural ; genetics ; therapy ; Humans ; Mice ; Mice, Inbred C57BL ; Stem Cell Transplantation

OBJECTIVETo investigate the effects of cycle-dependent kinase (CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia (AML) HL-60 cells and its molecular mechanisms.

METHODSCultured AML HL-60 cells were treated with various concentrations of SNS-032. Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK2/STAT3 pathway were detected by Western blotting.

RESULTSApoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9±1.7)%, (12.1±3.1)% and (59.4±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032. MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378c were down-regulated by SNS-032,whereas the levels of miR-320a and miR-H7* were up-regulated. Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT3 and protein expression of JAK2,C-MYC and MCL-1.

CONCLUSIONCDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family.

Apoptosis ; Cell Survival ; Down-Regulation ; Flow Cytometry ; HL-60 Cells ; Humans ; Janus Kinase 2 ; metabolism ; MicroRNAs ; metabolism ; Oxazoles ; pharmacology ; Phosphorylation ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Thiazoles ; pharmacology

UNLABELLEDObjective: To compare the clinical influence of intramedullary versus extramedullary alignment guides on total knee arthroplasty (TKA) in terms of alignment of the lower limbs,intraoperative tourniquet time,and postoperative complications.

METHODSWe retrospectively analyzed the clinical data of 105 patients(210 knees)undergoing bilateral TKA from February 2012 to November 2013. All patients were divided to two groups:40 [age:(66.65 ± 9.57)years] were implanted using intramedullary guides on the tibia and 65 [age:(65.29±9.27)years] were implanted using extramedullary guides on the tibia. Alignment of lower limb,tibial component angle in the sagittal plane,tourniquet time,and postoperative complications were compared.

RESULTSThe gender ratio,age,height,weight,body mass index,and preoperative alignment of lower limbs were not significantly different between these two groups (all P>0.05). The average coronal alignment of lower extremity was (179.69 ± 2.91)° in the intramedullary guides group and (178.26 ± 3.38)° in the extramedullary guides group (P=0.002). The alignment of lower limbs on neutral and valgus position were found in 68 cases(85.00%)in the intramedullary group and in 94 cases (72.31%) in extramedullary group (P=0.033) ;the tourniquet time was (79.46 ± 12.06) min in the intramedullary group and (84.68 ± 8.02) min in the extramedullary group (P=0.001); the postoperative complication rate was 6.25% in intramedullary group and 3.07% in extramedullary group (P=0.279).

CONCLUSIONAlignment and tourniquet time can be significantly improved by the intramedullary instrumentation,while the incidence of complications associated with intramedullary instrumentation is higher than extramedullary instrumentation.

Aged ; Arthroplasty, Replacement, Knee ; Humans ; Lower Extremity ; Postoperative Complications ; Retrospective Studies ; Tibia

OBJECTIVETo investigate whether CYC116 can potentiate matrine-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells.

METHODSThe dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an MTT assay and apoptosis induction was evaluated by flow cytometry. Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.

RESULTSMatrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor κB (NF-κB).

CONCLUSIONCYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.

Alkaloids ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Humans ; Multiple Myeloma ; pathology ; Pyrimidines ; pharmacology ; Quinolizines ; pharmacology ; Thiazoles ; pharmacology

OBJECTIVETo analyze the parameters of urodynamic tests for patients with type-III B prostatitis and evaluate the significance of the results of urodynamic tests in the choice of therapies for this disease.

METHODSUrodynamic tests were performed for 87 type-III B prostatitis patients aged 22-45 (30.7 ± 8.5) years, who had moderate or severe lower urinary tract symptoms (LUTS) and failed to respond to routine therapy. Different treatments were administered according to the results of urodynamic tests followed by observation of the therapeutic effects.

RESULTSUrodynamic abnormalities were found in 70 of the 87 patients, bladder outlet obstruction in 28 (32.2%), detrusor overactivity in 25 (28.7%), bladder hyperesthesia in 18 (20.7%), low compliance in 10 (11.5%), detrusor-external urethral sphincter dyssynergia in 1 (1.1%), and impaired detrusor contractile function in 1 (1.1%). Treatments achieved obvious effectiveness in 26 cases (29.9%), effectiveness in 51 (58.6%), and no effectiveness in 10 (11.5%).

CONCLUSIONUrodynamic tests contribute significantly to the choice of therapies for type-III B prostatitis patients with moderate or severe LUTS.

Adult ; Humans ; Lower Urinary Tract Symptoms ; physiopathology ; therapy ; Male ; Middle Aged ; Prostatitis ; physiopathology ; therapy ; Urethra ; physiopathology ; Urinary Bladder Neck Obstruction ; physiopathology ; Urinary Bladder, Overactive ; physiopathology ; Urodynamics

OBJECTIVETo evaluate the clinical results of using end plate rings in preventing subsidence of titanium cage in anterior cervical corpectomy and fusion (ACCF) surgery.

METHODSThe clinical data of 71 patients with cervical spondylotic myelopathy underwent ACCF in single segment from February 2008 to February 2011 were retrospectively analyzed. There were 38 males and 33 females, aged from 39 to 74 years old with a mean of 53.8 years. Thirty-three were used end plate rings and thirty-eight were not used (end plate rings group and no end plate ring group, respectively). The Japanese Orthopaedic Association (JOA) score, Odom's scale, imaging data were used to evaluate the clinical effects. Imaging data including Cobb angle of fusion segment, intervertebral height of anterior border (Da) and posterior border (Dp), the mean intervertebral height (Dm).

RESULTSAll patients were followed up from 13 to 34 months with an average of 19.5 months. Between two groups, there was no significant difference in Cobb angle of fusion segment and the mean intervertebral height (Dm) before surgery and one week after surgery. Whereas, one year after surgery, the Cobb angle of end plate ring group was (9.4 ± 3.8) degrees, and contral group was (7.5 ± 3.9) degrees, which was significantly lower than that of end plate ring group. Meanwhile, the Dm of end plate ring group was (57.3 ± 2.2) mm, and no end ring group was (55.2 ± 2.6) mm which was significantly lower than that of end plate ring group. The subsidence in end plate ring group was 57.6%, and was 78.9% in no end plate ring group. There was no significant difference in JOA score before and after surgery between two groups. At 1 year after operation, 90.9% (30/33) got excellent or good results in end plate ring group, 89.5% (33/38) got excellent or good results in contral group.

CONCLUSIONThe use of end plate rings could not completely prevent the subsidence of titanium cage, however, which can decrease the occurrence rate of the subsidence and lessen its degree.

Adult ; Aged ; Bone Plates ; Cervical Vertebrae ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Orthopedic Fixation Devices ; adverse effects ; Spinal Fusion ; instrumentation ; methods ; Spondylosis ; pathology ; surgery ; Titanium