AIMTo investigat the effects of donepezil on delayed rectifier-like potassium currents (IK) in rat hippocampus and neocortex.

METHODSWhole cell configuration of the patch-clamp techniques were used to characterize IK in acutely isolated rat hippocampal and neocortical pyramidal neurons.

RESULTSThe slowly inactivating outward currents (IK) were recorded in all cells under investigation. Donepezil in micromolar concentrations were shown to supress the IK of all cells in a dose-dependent and voltage-dependent manner. The steady-state activation curves of IK were characterized by half-activation potentials of -15.5 mV in hippocampal and -4.1 mV in neocortical pyramidal neurons and were changed to -26.2 mV and -18.6 mV, respectively, after perfusion with donepezil (10 mumol.L-1).

CONCLUSIONAt concentrations as low as 1 mumol.L-1, donepezil was found to block the IK in a voltage-dependent manner in hippocampus and neocortex. This effect may be synergistic with the anticholinesterase activity of donepezil to increase its therapeutic effectiveness.

Animals ; Cholinesterase Inhibitors ; pharmacology ; Delayed Rectifier Potassium Channels ; Hippocampus ; cytology ; In Vitro Techniques ; Indans ; pharmacology ; Male ; Neocortex ; cytology ; Neurons ; drug effects ; metabolism ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Potassium Channels ; drug effects ; physiology ; Potassium Channels, Voltage-Gated ; Pyramidal Cells ; drug effects ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo summarize the experience of laparoscopic common bile duct exploration.

METHODSThe clinical data of 587 cases who underwent laparoscopic common bile duct exploration from June 1992 to May 2006 were analyzed.

RESULTSThe surgery was successful in 585 cases (99.7%), 2 cases were converted to open common bile duct exploration. The duration of operation was 60 approximately 230 min (averaged 85 min), the complications consisted of biliary fistula (n=13), injury of the duodenum (n=1), abscess of drainage tube orifice (n=1), titanium clip discharging out from T tube (n=3), residual common bile duct stones (n=35). The patients could take food and walk on the second postoperative day and average postoperative hospital stay was 4.6 days.

CONCLUSIONSLaparoscopic common bile duct exploration is a safe and effective procedure in treating the calculus of bile duct.

Adult ; Aged ; Aged, 80 and over ; Biliary Tract Diseases ; surgery ; Biliary Tract Surgical Procedures ; methods ; Common Bile Duct ; surgery ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Retrospective Studies ; Treatment Outcome

BACKGROUNDWWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.

METHODSReverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.

RESULTSCompared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).

CONCLUSIONExpression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.

Acid Anhydride Hydrolases ; analysis ; genetics ; Breast ; pathology ; Breast Neoplasms ; genetics ; Chromosome Fragile Sites ; Female ; Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Neoplasm Proteins ; analysis ; genetics ; Oxidoreductases ; analysis ; genetics ; Tumor Suppressor Proteins ; analysis ; genetics ; WW Domain-Containing Oxidoreductase

Objective To investigate the epidemiological characteristics and the influencing factors of the unintentional injuries among Wenzhou elementary school children. Methods A total of 3 050 students were selected from the 1st to 6th grades in 6 primary schools in Wenzhou urban area by multi - stage sampling and were investigated during 2013 to 2015. Results 2 859 students completed the investigation. The morbidity of annual average unintentional injuries was 30. 81%(95% CI:29. 12% - 32. 50% )and the occurrence density was 2. 79. Unintentional injuries occurred mainly at home (37. 69% )and school(32. 39% ),and the most common site of injuries were leg(35. 02% )and hand(33. 79% ). For overall incidence,the slip falling injury(35. 64% )was highest,followed by cut or pierced(33. 40% )and crush injury (25. 08% ). Schoolgirl was a protective factor of the injury of crushed,electrical,traffic accident,bashed,burn , exploded,drown,poisoning and bit(OR ﹤ 1),but was a risk factor of multiple injuries(OR = 1. 323). Age was a risk factor of injury of fallen,crushed,bashed,burn,cut or pierced,exploded and bit(OR ﹥ 1. 1),but was a protective factor of poisoning(OR = 0. 671). compared with the students who walked to school alone,the children who were accompanied by their family member and rode alone to school were protective factors of the traffic accident. Conclusion The incidences of the unintentional injuries of elementary school children were increased with the age,and the boy was easier to be hurt. It was suggested for parents,schools and the government to strengthen healthy education for children at the early age.

Objective To investigate the variants and quasispecies of reverse transcriptase region in polymerase gene of hepatitis B virus (HBV) during lamivudine treatment and their relationship with genotypes and viral loads. Methods HBV DNA of 117 chronic hepatitis B patients treated with lamivudine were amplified by using PCR. The PCR products including the YMDD motif were sequenced by DNA sequencer, of which, HBV DNA viral loads of 99 patients were determined by real-time PCR and 64 samples were sequenced by Pyrosequencing. Results In HBV YMDD variant group and no variant group, the HBV genotypes were 79.6% and 86. 7% of type C, 18.5% and 12. 7% of type B, 1.9% of A/B recombinant type and 2.6% of type D, respectively. The viral loads ( log 10) were 6. 5699 and 6. 6165, respectively.There was no significant difference in HBV genotypes and viral loads between these two groups. The rtL180M variant was found in association with the rtM204I/V variant, HBV variants and wild-type in YMDD motif all existed together in these two groups. Conclusions HBV variants (quasispecies) in YMDD motif could be quantified by pyrosequencing, which would be a feasible measure during nucleoside or nucleotide analogue therapy against chronic HBV infection.

This study was aimed to investigate the expression of c-FLIPL, c-FLIPS and DLK1 mRNA in the patients with myelodysplastic syndrome (MDS) and its clinical significance. The mRNA expression of c-FLIPL, c-FLIPS and DLK1 in bone marrow mononuclear cells (BMMNC) of 16 patients with MDS and 3 controls were detected by RT-PCR. The results indicated that the expression of DLK1 mRNA was up-regulated in MDS, including RA and RAEB, as compared with controls (p < 0.05). There was no significant difference in expression of DLK1 between RA and RAEB patients (p > 0.05); the expression of c-FLIPL mRNA both in RA and RAEB patients was higher than that in controls (p < 0.05). There was no significant difference in expression of c-FLIPL between RA and RAEB patients (p > 0.05); the expression of c-FLIPS mRNA was not significantly different between MDS patients and controls (p > 0.05), but its expression in RAEB patients was significantly higher as compared with RA patients and controls (p < 0.05). It is concluded that the mRNA expressions of DLK1, c-FLIPL and c-FLIPS in MDS patients are abnormal, some of which may be useful as an important indicator for the evaluation of development in MDS.
Aged ; Bone Marrow Cells ; metabolism ; CASP8 and FADD-Like Apoptosis Regulating Protein ; genetics ; metabolism ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Myelodysplastic Syndromes ; genetics ; RNA, Messenger ; genetics

OBJECTIVEDendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs).

METHODSImmature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques.

RESULTSCompared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC.

CONCLUSIONHigh glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.

Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media ; Cytokines ; biosynthesis ; Dendritic Cells ; drug effects ; immunology ; metabolism ; Glucose ; adverse effects ; pharmacology ; Humans ; Immunophenotyping ; Monocytes ; cytology ; Reactive Oxygen Species ; metabolism ; T-Lymphocytes ; cytology

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers ; Cohort Studies* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Lymph Nodes ; Nasopharynx ; Plasma ; Prognosis ; Radiotherapy* ; Tumor Burden*

Objective: To evaluate the safety and clinical efficiency of holmium laser enucleation of the prostate (HoLEP) in the treatment of small-volume BPH (SBPH) complicated by severe lower urinary tract symptoms (LUTS). METHODS: We retrospectively analyzed the clinical data on 82 cases of SBPH with severe LUTS treated by HoLEP from January 2017 to December 2018. The patients were aged (65.5 ± 7.6) years, with a mean prostate volume of <40 ml, a total IPSS of 24.8 ± 4.6, a QOL score of 5.2 ± 0.8, the maximum urinary flow rate (Qmax) of (7.6 ± 3.7) ml/s, and a mean PSA level of (1.8 ± 1.4) μg/L. RESULTS: All the operations were successfully completed, the mean operation time averaging (30.2 ± 5.0) min, enucleation time (26.7 ± 5.6) min and comminution time (3.5 ± 1.1) min, and the enucleated tissue weighing (20.3 ± 4.9) g. After surgery, the bladders were irrigated for (3.5 ± 1.9) h, with (3.0 ± 1.7) L of rinse solution, and catheterization lasted (24.8 ± 9.7) h. Histopathology revealed moderate or severe lymphocytic infiltration in 69 cases (84.1%). At 6 months after operation, significant improvement was observed in the IPSS, QOL, Qmax and PSA level compared with the baseline (P < 0.05). To date, no urethral stricture-related reoperation was ever necessitated. CONCLUSIONS HoLEP is safe and effective for the treatment of SBPH complicated by severe LUTS and can be employed after adequate preoperative evaluation of the patient.《.
Humans ; Lasers, Solid-State ; Lower Urinary Tract Symptoms/surgery* ; Male ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Retrospective Studies

Objective: To investigate the clinical effect of "3+1" bladder function restoration combined with holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with acontractile detrusor (ACD). METHODS: We treated 35 BPH patients with ACD by HoLEP followed by "3+1" bladder function restoration, that is, a 3-phase bladder function training plus simultaneous 1-drug medication after surgery. We recorded and analyzed the detrusor pressure, post-void residual urine volume (PVR), maximum urinary flow rate (Qmax), International Prognostic Scoring System (IPSS) scores, quality of life (QoL), voluntary micturition, satisfaction with the bladder function, hydronephrosis, ureterectasia, renal function, and urinary tract infection of the patients before and after treatment. RESULTS: Compared with the base line, at 6 months treatment, the patients showed significantly increased detrusor pressure (［35.1±2.7］vs ［50.2±2.3］ cmH2O, P<0.05) and Qmax (［4.2±2.7］vs ［21.1±4.1］ ml/s, P<0.05) but decreases in PVR (［173.0±31.6］ vs ［30.5±12.9］ml, IPSS score (27.3±3.2 vs 5.1±1.4, P<0.05) and QoL (4.1±0.8 vs 0.8±0.1, P<0.05), elevated rates of voluntary urination (0% ［0/35］ vs 100% ［35/35］, P<0.05), regularurination (0% ［0/35］ vs 85.71% ［30/35］, P<0.05), grade Ⅰ satisfaction with bladder function (0% ［0/35］ vs 85.71% ［30/35］, P<0.05), reduced rate of overflowing urinary incontinence (28.57% ［10/35］ vs 5.71% ［2/35］, P<0.05), and increased percentages of normal renal function (34.29% ［12/35］ vs 85.71% ［30/35］, P<0.05) and non-infection of the urinary system (17.14% ［6/35］ vs 94.29% ［33/35］, P<0.05). After treatment, urination was markedly improved in 94.29% (33/35) of the patients. CONCLUSIONS "3+1" bladder function restoration combined with HoLEP produced a desirable effect on BPH with ACD, though its long-term effect remains to be further investigated.
Aged ; Holmium ; Humans ; Laser Therapy ; methods ; Lasers, Solid-State ; Male ; Personal Satisfaction ; Prostatic Hyperplasia ; surgery ; Quality of Life ; Recovery of Function ; Transurethral Resection of Prostate ; methods ; Treatment Outcome ; Urinary Bladder ; physiology ; Urination ; physiology