N6-methyladenosine (m6A) is one of the most abundant modifications on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex (MTC) containing a key factor methyltransferase-like 3 (Mettl3). How-ever, the functions of Mettl3 and m6A modification in hepatic lipid and glucose metabolism remain unclear. Here, we showed that both Mettl3 expression and m6A level increased in the livers of mice with high fat diet (HFD)-induced metabolic disorders. Overexpression of Mettl3 aggravated HFD-induced liver metabolic disorders and insulin resistance. In contrast, hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain, reducing lipid accumulation, and improving insulin sensitivity. Mechanistically, Mettl3 depletion-mediated m6A loss caused extended RNA half-lives of metabolism-related genes, which consequently pro-tected mice against HFD-induced metabolic syndrome. Our findings reveal a critical role of Mettl3-mediated m6A in HFD-induced metabolic disorders and hepatogenous diabetes.

OBJECTIVETo summarize the 5-year follow-up to 2 micron continuous wave laser vaporesection for the treatment of patients with low urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), and evaluate the safety and clinical effects of the treatment.

METHODSFrom October 2006 to September 2007, 236 cases with low urinary tract symptom secondary to BPH were treated transurethrally under epidural or general anesthesia using the 70 Watt 2 micron laser system. Vaporesection of the prostate was performed with the traditional "U" or the "dividing" method. The 210 cases who met the inclusion criteria in this study were selected for further observation. Baseline and perioperative data were recorded and evaluated in resection time, transfusion rate, catheter-time, improvements in maximal urinary flow rate (Qmax), international prostate symptom scores (IPSS), quality of life (QoL), and post voiding residual volume (PVR).

RESULTSOut of the 210 cases, 179 cases were followed up to 5 years finally. All the surgical procedures were successfully conducted under epidural or general anesthesia. Mean operation time was (80 ± 22) minutes, and mean retrieved prostatic tissue was (24.9 ± 4.2) g. Resected prostatic tissues could be easily flashed out of the bladder. There were no significant differences in serum sodium concentrations and hemoglobin levels before and after the surgery. Mean catheter time and hospital stay was (114 ± 35) hours and (5.7 ± 1.9) days respectively. Only one postoperative secondary hemorrhage was found and treated with blood transfusion. During the 5-year follow-up, Qmax increased from (8.6 ± 3.5) ml/s preoperatively to (23.6 ± 4.2) ml/s by the end of the follow-up (P < 0.01), IPSS and QoL-Score improved from 25.3 ± 5.2 and 4.1 ± 1.3 to 6.1 ± 3.0 and 1.4 ± 0.8 respectively (P < 0.01), and PVR decreased from (248 ± 89) ml to (15 ± 13) ml. The 3 patients developed urinary incontinence and recovered 3 months later through functional exercises with the help of acupuncture. Five patients were found to have urethral stricture 3 months after the surgery and recovered with the treatment of urethral dilatation (3 cases) or internal urethrotomy (2 cases) respectively.

CONCLUSIONSTransurethral vaporesection of prostate using the 2 micron continuous wave laser system is a safe and effective treatment for benign prostatic hyperplasia with obvious improvements in subjective and objective voiding parameters, which were evident at 3 months after the surgery and were sustained throughout the 5-year long-term follow-up.

Aged ; Aged, 80 and over ; Follow-Up Studies ; Humans ; Laser Therapy ; Male ; Middle Aged ; Postoperative Complications ; Prostatic Hyperplasia ; surgery ; Transurethral Resection of Prostate ; methods

BACKGROUNDPatients with single station mediastinal lymph node (N2) non-small cell lung cancer (NSCLC) have a better prognosis than those with multilevel N2. The molecular factors which are involved in disease progression remain largely unknown. The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.

METHODSGene expression analysis was performed using Agilent 4×44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients. Real-time reverse transcription (RT)-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed. Immunohistochemical staining for these validated genes was performed on formalin-fixed, paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.

RESULTSWe identified a 14 gene expression signature by comparative analysis of gene expression. Expression of these genes strongly differed between single station and multilevel N2 NSCLC. Four genes (ADAM28, MUC4, CLDN1, and IGF2) correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients. Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.

CONCLUSIONSOur results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC. Further, CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; pathology ; Claudin-1 ; analysis ; genetics ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor II ; analysis ; genetics ; Lung Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis

OBJECTIVETo understand the clinical features of death from hand, foot and mouth disease (HFMD) and to explore the early warning index of HFMD death.

METHODSA total of 41 HFMD death cases were collected as case group in Shandong province between 2009 and 2011, and another 123 serious HFMD cases were selected as control group according to the similar gender, place of origin and hospital level, with the ratio at 1:3. We investigated the general situation, clinical treatment, past medical history, clinical symptoms and signs of the ill children, and applied the conditional logistic regression to explore early warning index of HFMD death.

RESULTSThe rate of patients who had symptoms in nervous system, digestive system, circulatory system and respiratory system were separately 90.2% (37/41), 58.5% (24/41), 53.7% (22/41) and 90.2% (37/41) in case group; and the proportions were 44.7% (55/123), 13.8% (17/123), 10.6% (13/123) and 12.2% (15/123) respectively in control group. The difference between the two groups showed statistical significance (χ(2) = 25.881, 32.791, 34.011, 86.505, P < 0.05). In case group, 37 patients had neurogenic pulmonary edema, 26 patients got encephalitis, 15 patients had respiratory and circulatory failure, 7 patients got pulmonary hemorrhage, 4 patients had multiple organ failure, 4 patients got myocarditis and 1 patient had cerebral hernia. According to multi-factor logistic regression analysis, the early warning indicators of HFMD death included neck resistance (case group: 34.1% (14/41), control group: 4.1% (5/123); OR = 7.145, 95%CI: 1.748 - 29.204), vomiting (case group: 58.5% (24/41), control group: 13.8% (17/123); OR = 5.632, 95%CI: 1.793 - 17.685) and increase of heart rate (case group: 53.7% (22/41), control group: 10.6% (14/123), OR = 6.370, 95%CI: 1.517 - 26.743).

CONCLUSIONIn the process of clinical treatment and care, we should interfere the serious HFMD patients with neck resistance, vomiting and increase of heart rate, and thereby reduce the death from HFMD.

China ; epidemiology ; Female ; Hand, Foot and Mouth Disease ; diagnosis ; epidemiology ; mortality ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Risk Factors ; Survival Rate

BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.

METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.

RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.

CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology

Objective To explore the relationship between genetic polymorphisms of CACNA1C that encoded the alc subunit of the L-type calcium channel and the efficacy of calcium channel blocker (CCB,Nifedipine extended release tablet/20 mg/d)in essential hypertension(EH)patients of Han Chinese in Wenzhou.Methods For the enrolled 103 EH patients,Multiplex Polymerase Chain Reaction(Muhi PCR)and matrix assisted laser desorption ionization time of flight MS(MLD1-TOF MS)were performed to detect their genotypes(rs216008,rs1051375,rs2299661,rs10848683,rs215976),blood pressure(BP)after CCB monotherapy was compared among patients with different genotypes.Results(1)Blood pressure was significantly reduced in all patients post CCB(P ＜ 0.05 vs.pre-CCB).(2)Diastolic blood pressure reduction was more significant in subjects with rs2299661 C/C genotype(wild genotype)than in subjects with rs2299661C/G and rs2299661G/G genotype(mutational genotype)[(12.46 ± 7.91)mm Hg (1 mm Hg=0.133 kPa)vs.(7.22±8.01)mm Hgand(5.93 ± 9.77)mm Hg,P＜0.05].(3)Systolic blood pressure reduction was more significant in subjects with rs216008 C/C genotype(wild genotype)than in subjects with rs216008 C/T genotype(mutational genotype)[(20.60 ± 12.35)mm Hg vs.(13.62 ±10.21)mm Hg,P ＜0.05].(4)Blood pressure reduction was similar between subjects with genotype of rs1051375,rs10848683 and rs215976.Conclusion EH patients with wild genotype of rs2299661 and rs216008 in CACNA1 C are more likely to be responders of CCB monotherapy.

OBJECTIVESTo observe the vaporesection efficiency of the 2 micron laser to the prostatic gland in benign prostatic hyperplasia, and investigate the method of estimating the amount of the vaporesected prostatic tissues during transurethral vaporesection of the prostate using the 2 micron laser system in the treatment of benign prostatic hyperplasia.

METHODSTotal 9 fresh prostatic gland specimens were obtained from patients with BPH under open surgical procedures, and vaporesected under a simulated transurethral environment with the 2 micron laser system immediately after weighted. Energies and time consumptions were noted, collections of vaporesected tissue specimens and the remnants of the prostatic glands were weighted after the procedures. The ratios of the vaporized tissues and the collected tissues to the whole vaporesected tissues were calculated respectively. The vaporesection efficiency of the 2 micron laser to the prostatic tissues was also calculated.

RESULTSAmong the total lost tissues, about (65.6 +/- 1.5) percent of which were that of vaporized, and nearly (34.5 +/- 1.5) percent were resected. Linear correlation between the weight of collected prostatic tissue(x) and the weight of prostatic gland specimens(y) could be defined as a formula of [y = 3.245x - 6.475 (t = 15.097, P = 0.000)].

CONCLUSIONThe amounts of the whole prostatic tissues removed by the 2 micron laser could be calculated from the collected resected prostatic specimens under a simulated transurethral surgical procedure.

Humans ; In Vitro Techniques ; Laser Therapy ; methods ; Lasers ; Male ; Prostate ; surgery ; Prostatic Hyperplasia ; surgery ; Transurethral Resection of Prostate ; methods

BACKGROUNDThe safety and efficiency of transurethral laser resection of the prostate to treat benign prostatic hyperplasia have been verified. However, this method does still not manage large volume prostates efficiently. To tackle this problem, we have designed a method of "transurethral dividing vaporesection of prostate" using a 2 micron continuous wave laser. The aim of this study was to evaluate the safety and efficiency of this method in the management of large prostates (> 80 ml).

METHODSIn this study, 45 cases of benign prostatic hyperplasia with a median prostatic volume of (123.7 ± 26.7) ml (range, 80.2-159.8 ml) were treated by the same surgeon under epidural anesthesia. During the surgery, superapubic catheters were needed, and saline solution was used for irrigation. First, the prostate was divided longitudinally into several parts from the bladder neck to the prostatic apex, and then gradually incised transversely chip by chip. Intraoperative blood transfusion rate, postoperative complications, maximum urinary flow rate, International Prostate Symptom Score and quality of life scores were recorded for statistical analysis using SPSS 16.0 software.

RESULTSIntraoperatively, no transurethral resection syndrome was observed, and no blood transfusions were needed. The resected prostatic chips were easily flushed out of the bladder through the resectoscope sheath without the use of a morcellator. Median vaporesection time was (95.0 ± 13.2) minutes (range, 75-120 minutes), and the median retrieved and removed prostatic tissue were (25.2 ± 5.1) g (range, 15.5-34.7 g) and (75.4 ± 16.4) g (range, 43.8-106.1 g), respectively. Median catheter time and hospital stay were (3.3 ± 0.9) days (range, 3-5 days) and (4.8 ± 1.8) days (range, 3-9 days), respectively. After a follow-up of 6 to 12 months, two patients had stress urinary incontinence and three had anterior urethral strictures. Satisfactory improvement was seen in maximum urinary flow rate, International Prostate Symptom Score and quality of life scores.

CONCLUSIONSThis study showed that 2 micron laser vaporesection is a safe treatment for benign prostatic hyperplasia patients with large prostates, and the method of "dividing vaporesection" may help improve both surgical efficiency and patient outcomes.

Aged ; Aged, 80 and over ; Follow-Up Studies ; Humans ; Laser Therapy ; methods ; Male ; Middle Aged ; Prostatic Hyperplasia ; pathology ; surgery ; Transurethral Resection of Prostate

OBJECTIVETo investigate the situation of overactive bladder (OAB) in a community-based male population.

METHODSMale participants over 50 years old were randomly selected from multiple communities in Beijing. The evaluation of lower urinary tract symptoms (LUTS) including the International Prostate Symptom Score (IPSS), quality of life (QOL) score, prostate volume and post voiding residue (PVR) by abdominal ultrasonography, and maximum flow rate (Qmax). Definition of OAB was determined as the score of item number 4 in IPSS ≥ 2.

RESULTSOf 1656 male participants enrolled, a total of 1639 men met our study criteria. The mean age was (64 ± 10) years. The prevalence of OAB was 26.3% (431/1639), and was significantly related to age, IPSS, QOL score, prostate volume, PVR and Qmax (P < 0.01). The prevalence of OAB was closely associated with aging (P < 0.01) and the degree of LUTS (P < 0.01).

CONCLUSIONSThe prevalence of OAB increased with aging of the community-based male population. OAB would obviously affect the quality of life of the aging men.

Aged ; Aged, 80 and over ; Aging ; China ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Quality of Life ; Urinary Bladder, Overactive ; epidemiology