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Objectives: To investigate the expression of miR -429 and its target gene heat shock protein A4L ( HSPA4L ) in sperms from asthenospermia patients., Methods: Twenty semen samples from healthy and fertile adults and 20 semen samples from asthenospermia patients were collected,and normal sperm parameters were defined according to World Health Organization criteria.The expression levels of miR -429 and HSPA4L mRNA were determined by qRT-PCR,and the bioinformatics tool (Targetscan) was used to predict the target of miR -429.Luciferase reporter assay and transfection study were performed to confirm target gene of miR -429.The expression levels of HSPA4L mRNA and protein were further determined by qRT-CPR and Western blot,respectively., Results: The motility and viability of sperms from asthenospermia patients were lower than that in control group,and miR -429 was up-regulated in sperms from asthenospermia patients.Bioinformatics analysis revealed that HSPA4L was a target of miR -429.Luciferase reporter assay and transfection study further confirmed that miR -429 suppresses the expressions of HSPA4L mRNA and protein via directly targeting HSPA4L 3'UTR.Results from clinical samples also demonstrated that HSPA4L mRNA and protein were down-regulated in sperms from asthenospermia patients and the expression level of miR -429 was inversely correlated with the expression level of HSPA4L mRNA ( r =-0.725, P <0.05)., Conclusions: miR -429 is up-regulated in sperms from asthenospermia patients,and it may modulate the motility and viability of sperms via suppressing the expression of HSPA4L .

Aim: To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM)., Methods: This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups., Results: Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five-year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group., Conclusion: Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths.

The aim of the present study was to investigate the association between O6-methylguanine-DNA methyltransferase (MGMT) gene expression levels, and DNA methylation status and histone modifications in laryngeal squamous cell carcinoma (LSCC). Chromatin immunoprecipitation, methylation-specific polymerase chain reaction (PCR), and reverse transcription-quantitative PCR were performed to analyze histone modifications, DNA methylation status and mRNA expression levels in the promoter region of the MGMT gene in laryngeal carcinoma HEp-2 cells, as well as in 50 paired healthy and LSCC tissue samples. The present study demonstrated that treatment of HEp-2 cells with 5-aza-2'-deoxycytidine (Aza), a DNA methyltransferase inhibitor, significantly upregulated MGMT mRNA expression levels, reduced MGMT DNA methylation, reduced MGMT histone H3 lysine 9 (H3K9) di-methylation, and increased MGMT histone H3 lysine 4 di-methylation without a significant change in H3K9 acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, marginally upregulated MGMT mRNA expression levels without affecting the DNA methylation status, or H3K9 or H3K4 di-methylation, however, TSA treatment caused a significant increase in H3K9 acetylation. Furthermore, Aza and TSA combination treatment produced a synergistic effect. In the LSCC samples, the rate of DNA methylation in the MGMT gene was 54%, compared with 24% in the healthy control group (P<0.05). Therefore, data from the present study indicates that MGMT may serve as a novel therapeutic target in the treatment of LSCC.

Objective: To observe the effect and safety of supplying sodium chloride in the treatment of patients with severe heart failure., Methods: Consecutive 51 hospitalized patients with severe heart failure and cardiac edema were included in this study. Normal diet (6 g NaCl/d) was supplied to all patients. On the basis of controlling fluid intake and treating related etiological factors as well as standard medications including furosemide for severe heart failure, patients with mild hyponatremia (serum sodium level 130 - 134 mmol/L) ate additional salted vegetables, patients with moderate hyponatremia (serum sodium level 125 - 129 mmol/L) and severe hyponatremia (serum sodium level < 125 mmol/L) ate additional salted vegetables and were received additionally intravenous 3%NaCl hypertonic saline infusion (10 ml/h) until reaching normal serum sodium level., Results: On admission, 37.25% (19/51) patients had hyponatremia. During the first two weeks hospitalization period, 88.24% (45/51) patients were treated with intravenous diuretics and total incidence of hyponatremia was 64.71% (33/51), mild hyponatremia was 50.98% (26/51), middle and severe hyponatremia was 13.73% (7/51); among them, hyponatremia lasted less than 3 d in 57.58% (19/33) patients and ≥ 3 d in 42.42% (14/33) patients. Heart failure exacerbation and hypernatremia were not observed in patients receiving additional sodium chloride therapy. Hospitalization time was similar among patients with different blood natrium levels [average (16 ± 12) d]. Fifty out of 51 (98%) patients discharged from the hospital with improved heart failure symptoms and signs., Conclusion: Supplying additional sodium chloride could rapid correct hyponatremia in heart failure patients with or without intravenous diuretics therapy which might contribute to a favorable prognosis in hospitalized heart failure patients.

Objective: To investigate the relationship between RASSF1A gene expression and DNA methylation or histone modification in laryngeal carcinoma tissues., Methods: Chromatin immunoprecipitation (ChIP), methylation specific polymerase chain reaction (MSP) and realtime quantitative reverse transcription polymerase chain reaction (realtime RT-PCR) were used to analyze RASSF1A gene promoter region histone H3 lysine 9 methylation, H3 lysine 4 methylation, H3 lysine 9 acetylation, DNA methylation, and RASSF1A gene expression in laryngeal carcinoma tissue of 50 cases., Results: DNA methylation rate of gene RASSF1A was 62% in 50 cases of laryngeal carcinoma, but no DNA methylation was found in normal control group, with a significant difference (χ(2) = 15.381, P < 0.05). DNA methylation had no correlation with age, gender, differentiation degree, T stage, pathological type and lymph node metastasis (P > 0.05). The affection of DNA methylation group was more than unmethylation group to expression of gene RASSF1A (t = -3.108, P < 0.01). There was positive correlation between RASSF1A deletion and gene hypermethylation or between H3 lysine 9 methylation of RASSF1A gene promoter and DNA methylation in laryngeal carcinoma tissue(r = 0.816, P < 0.05), but there was negative correlation between H3 lysine 4 methylation of RASSF1A gene promoter and DNA methylation (r = -0.837, P < 0.05) and no correlation between H3 lysine 9 acetylation and DNA methylation (r = -0.383, P > 0.05)., Conclusions: Laryngeal tumor suppressor gene RASSF1A promoter methylation is a key factor down-regulating the gene expression, and histone modifications also plays an important role in tumor development.

Objective: To sum up the experience in the treatment of obstructive azoospermia by intracytoplasmic sperm injection (ICSI)., Methods: We retrospectively analyzed 107 cases of obstructive azoospermia treated by ICSI in our center from Jan. 2006 to Dec. 2008, and compared the rates of fertilization, cleavage and pregnancy between the patients with congenital bilateral absence of vas deferens (CBAVD) and those with non-CBAVD., Results: A total of 949 oocytes were injected for the 107 patients undergoing ICSI, of which 678 (71.4%) were fertilized and 605 (89.2%) cleaved, with 44 pregnancies (41.4%). Of the 442 oocytes injected for the 49 patients with CBAVD, 308 (69.6%) were fertilized and 279 (90.6%) cleaved, with 27 pregnancies (55.1%), and of the 507 oocytes injected for the 58 cases induced by inflammation or surgery, 370 (72.9%) were fertilized and 326 (88.1%) cleaved, with 17 pregnancies (29.3%). The rate of pregnancy was significantly higher in the CBAVD than in the non-CBAVD group (P < 0.01), but there were no significant differences in the rates of fertilization and cleavage between the two groups (P > 0.05)., Conclusion: PESA or TESE combined with ICSI is an effective approach to the treatment of male infertility induced by obstructive azoospermia, which may achieve a higher rate of pregnancy in patients with CBAVD than in those with non-CBAVD. Inflammation or surgery may not only cause the obstruction of the deferent duct, but also affect sperm quality, and consequently reduce the potentiality of embryonic development.