PURPOSE: To investigate long-term therapeutic effects and patient adherence to a combination therapy of a 5α-reductase inhibitor and an α-blocker and to identify causes of withdrawal from medication in patients with clinical benign prostatic hyperplasia (BPH). METHODS: BPH patients with lower urinary tract symptoms (LUTS) receiving combination therapy with follow-ups for 1–12 years were retrospectively analyzed. Therapeutic effects were assessed at baseline and annually by measuring International Prostatic Symptoms Score, quality of life index, total prostate volume (TPV), maximal flow rate, voided volume, postvoid residual volume and prostate-specific antigen level. Causes of discontinued combination therapy were also investigated. RESULTS: A total of 625 patients, aged 40–97 years (mean, 73 years) were retrospectively analyzed. All measured parameters showed significant improvements after combination therapy. Three hundred sixty-nine patients (59%) discontinued combination therapy with a mean treatment duration of 2.2 years. The most common reasons for discontinued treatment were changing medication to monotherapy with α-blockers or antimuscarinics (124 patients, 19.8%), receiving surgical intervention (39 patients, 6.2%), and LUTS improvement (53 patients, 8.5%). Only 64 patients (10.2%) were loss to follow-up and 6 (1.0%) discontinued combined treatment due to adverse effects. Smaller TPV after short-term combination treatment caused withdrawal from combination therapy. CONCLUSIONS: BPH patients receiving long-term combination therapy showed significant improvement in all measured parameters. Changing medication, improved LUTS and choosing surgery are common reasons for discontinuing combination herapy. A smaller TPV after short-term combination treatment was among the factors that caused withdrawal from combination therapy.
Adrenergic alpha-1 Receptor Antagonists ; Follow-Up Studies ; Humans ; Lower Urinary Tract Symptoms ; Medication Adherence ; Muscarinic Antagonists ; Patient Compliance* ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Quality of Life ; Residual Volume ; Retrospective Studies ; Therapeutic Uses

BACKGROUNDStudies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients.

METHODSIn a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured.

RESULTSBoth asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients -0.468, -0.478, and -0.426, respectively).

CONCLUSIONSThe concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.

Administration, Inhalation ; Adult ; Asthma ; drug therapy ; physiopathology ; Breath Tests ; Budesonide ; administration & dosage ; Female ; Forced Expiratory Volume ; Humans ; Interleukin-4 ; analysis ; Interleukin-6 ; analysis ; Male ; Middle Aged ; Peak Expiratory Flow Rate ; Prospective Studies

OBJECTIVETo investigate curative effects of elastic stable intramedullary nails in the treatment of stable and unstable fractures of femoral shaft in children and to guide its clinical application.

METHODSFrom January 2008 to October 2010,44 children with femoral shaft fractures were treated,including 24 boys and 20 girls,ranging in age from 5 to 12 years, with an average of 7.4 years. Based on the fractures stable or not, the patients were divided into stable fractures group(group S) and unstable fractures group (group U). All the children received the same operation to fix broken femoral with elastic stable intramedullary nails and some children received traction or small splint protection after operation when reduction and fixation were considered unsatisfied or his/her weight beyond 30 kg. During the followed-up, the healing time, irritation of the soft tissue (ache, cyst, t al), malunion (angulation above 5 degree in X-ray), limb shortening or lengthening and excellent and good rate were observed.

RESULTSAll the patients were followed up,and the duration ranged from 5 to 19 months, with an average of 13 months. All the fractures were healed at the latest follow-up. The average healing time was 10.2 weeks (ranges, 8 to 14 weeks). The incidence rate of malunion was 23.8% in group U and the average angulation was 9 degree (6 to 12 degree), which was higher than those of patients in the group S (0%). The average healing time, limb shortening or lengthening, irritation of the soft tissue and the excellent and good rate between two groups had no significance differences, which were (10.6 +/- 1.3) vs. (9.9 +/- 1.2) weeks, 0 vs. 3 cases, 3 vs. 1 case and 2 vs. 4 cases respectively. In the group U, among 5 patients had malunion, 4 patients were not treated with traction or small splint protection,and the incidence was higher than those who were given traction or small splint protection.

CONCLUSIONBoth the stable and unstable femoral shaft fractures in children treated with elastic stable intramedullary nails can receive well short-term curative effects. If given certain postoperative protection like as traction or small splint, the malunion incidence can be reduced.

Bone Nails ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Femoral Fractures ; surgery ; Fracture Fixation, Intramedullary ; instrumentation ; Humans ; Male ; Treatment Outcome

BACKGROUNDThe number of Clara cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.

METHODSEighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS + NAC group) oral intake of NAC 80 mg x kg(-1) x d(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The mRNA expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.

RESULTSCompared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3 +/- 14.7 vs. 53.7 +/- 11.5, P < 0.05). The Clara cell particles in cytoplasm decreased in the CS group (P < 0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8 +/- 4.3 and 29.5 +/- 2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1 +/- 3.8 and 43.8 +/- 5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P < 0.05). No significant difference was observed in GSH level ((181 +/- 26) nmol/L in the control group vs. (170 +/- 18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1 +/- 17.5) decreased (P < 0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213 +/- 40) nmol/L vs. (170 +/- 18) nmol/L in the CS group) increased too (P < 0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1 +/- 6.4 and 34.3 +/- 6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P > 0.05). No significant difference was found in the expression of CC16 mRNA among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r = -0.592, P < 0.05), but not with GSH level.

CONCLUSIONSOne-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.

Acetylcysteine ; metabolism ; Animals ; Bronchioles ; cytology ; drug effects ; metabolism ; Fluorometry ; Glutathione ; metabolism ; Immunohistochemistry ; Male ; Microscopy, Electron, Transmission ; Random Allocation ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Smoking ; adverse effects ; Uteroglobin ; genetics ; metabolism

INTRODUCTIONTo investigate the attitudes of medical and nursing student towards the older Chinese population.

MATERIALS AND METHODSA reliable and valid Chinese language version of Kogan's Attitudes toward Older People (KAOP) with 17 matched item pairs (34 items) was completed by 275 medical and nursing students. Descriptive data analysis was employed.

RESULTSParticipants reported slightly to have a more positive attitudes (Mean, 144.30 +/- 17.89) than those reported from studies in other countries (Jordanian: Mean, 110.6 +/- 21.79). Students who were females (Mean, 148.27 +/- 18.97), younger (Mean, 146.01 +/- 18.59) and studying nursing (Mean, 156.86 +/- 17.56) were more likely to have a more positive attitudes than older (Mean, 140.04 +/- 15.31), males (Mean, 140.47 +/- 15.93), studying medicine (Mean, 138.77 +/- 15.04).

DISCUSSIONResults show that students may have greater ambivalence attitudes on 10 out of 17 matched item pairs which provides useful information for faculty involved in aged care curriculum design. Working as a volunteer in the university hospital may increase students' interactions with the elderly and may positively influence attitudes towards the elderly.

Aged ; Attitude of Health Personnel ; Female ; Humans ; Male ; Students, Medical ; psychology ; Students, Nursing ; psychology ; Taiwan

OBJECTIVE: Hypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings. METHODS: Cervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR). RESULTS: The degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2. CONCLUSION: Our study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.
Cervical Intraepithelial Neoplasia* ; DNA Methylation ; Epigenomics ; Genome ; Genotype ; Human papillomavirus 16 ; Humans ; Methylation* ; Papillomaviridae ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms

Background: Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. Results: The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37–38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. Conclusions We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

Objective To observe serum uric acid (UA) level distribution and explore risk factors of hyperuricemia (HUA) in a large cohort of active and retired employees underwent physical examination.Methods Physical examination was arranged for 21 700 active and retired employees from May 2010 to September 2011,16 416 employees were examined and complete examination data were obtained in 14 044 subjects.The distribution characteristics of UA level and correlations of UA level and HUA prevalence rate with gender,age,body mass index (BMI),systolic pressure (SBP),diastolic pressure (DBP),fasting blood-glucose (FPG),serum total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C) were analyzed.Results HUA prevalence rate was 11.2％ in this cohort,which was significantly higher in males (15.8％) than in females (4.1％,P ＜ 0.05).The UA level and the HUA prevalence rate presented a “J” curve relationship with aging and positively correlated with BMI,SBP,DBP,TG,LDL-C,TC and FPG while negatively correlated with HDL-C.Multiple linear regression analysis showed that SBP,BMI,FPG,TG,and LDL-C were independent risk factors while HDL-C and female gender were the protective factors of HUA(all P ＜0.01).Aging and high DBP were independent risk factors of HUA for females (all P ＜ 0.05)and LDL-C was risk factor of HUA for males (P ＜ 0.05).Conclusions Serum UA level presents a “J” wave relationship with aging.The risk factors of HUA are increased SBP,BMI,FPG,TG,LDL-C while the protective factors of HUA are female gender and high HDL-C.

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition.Moreover, EVs decreased the lipid accumulation rate during adipogenic induction.

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 µM and 17.8 µM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.
Acetylcysteine ; Antineoplastic Agents ; Apoptosis Regulatory Proteins ; Apoptosis* ; Arthritis, Rheumatoid ; Cell Line ; Elaeagnaceae ; Fibroblasts ; Humans ; Lung ; Membrane Potential, Mitochondrial ; Mouth Neoplasms* ; Plants, Medicinal ; Reactive Oxygen Species