RESUMO
OBJECTIVE: To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity. METHODS: Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively. RESULTS: DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05). CONCLUSION: DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.
Assuntos
Doxiciclina , Mieloma Múltiplo , Apoptose , Caspase 3 , Caspase 9/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Doxiciclina/farmacologia , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologiaRESUMO
OBJECTIVE: To investigate the factors influencing the recovery from childhood inguinal herniorrhaphy (IH)-induced vas deferens obstruction following microscopic vasovasostomy. METHODS: We retrospectively analyzed the clinical data on 41 cases of microscopic vasovasostomy for obstructive azoospermia in our hospital from July 2015 to September 2018. All the patients had a history of inguinal hernia treated by IH in the childhood. We performed scrotal ultrasonography, semen analysis and seminal plasma biochemistry to confirm vas deferens obstruction preoperatively. If sperm was observed for ≥2 times in semen examination after vasovasostomy, we considered the vas deferens successfully unobstructed. RESULTS: Microscopic vasovasostomy was successfully completed in 39 of the cases, of which2 were lost to follow-up, with a follow-up rate of 94.8% (37/39). The patients, at the mean age of (25.54 ± 2.85) years and with body mass index (BMI) of (24.92 ± 2.79) kg/m2 and post-IH time of (18.97 ± 2.58) years, were followed up for (13.05 ± 3.74) months. Successful recovery from vas deferens obstruction was observed in 78.4% (29/37) of the patients after IH, 80.0% (16/20) in the < 26-year-olds, 76.5% (13/17) in the ≥26-year-olds (P = 0.795), 75.0% (12/16) in those with BMI < 24.92 kg/m2 , 81.0% (17/21) in those with BMI ≥24.92 kg/m2 (P = 0.807), 78.6% (11/14) in those with post-IH time of < 19 years, 18.3% (18/23) in those with post-IH time of ≥19 years (P = 0.982), 60.0% (12/20) in those with sperm and 82.4% (14/17) in those without sperm found intraoperatively (P = 0.428), 42.9% (3/7) in those treated by unilateral and 82.4% (26/30) in those by bilateral vasovasostomy (P = 0.027). Multivariate logistic regression analysis showed a close correlation between the operation side and postoperative recovery from vas deferens obstruction (P = 0.022). CONCLUSIONS: For male patients undergoing microscopic vasovasostomy for childhood IH-induced vas deferens obstruction, the operation side is an independent factor influencing postoperative recovery, while age, BMI, post-IH time, and intraoperative presence or absence of sperm are not significantly correlated with it.
Assuntos
Doenças dos Genitais Masculinos/cirurgia , Hérnia Inguinal/complicações , Ducto Deferente/cirurgia , Vasovasostomia , Adulto , Criança , Doenças dos Genitais Masculinos/etiologia , Herniorrafia , Humanos , Masculino , Estudos Retrospectivos , Ducto Deferente/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To investigate the correlation between male libido and the levels of serum reproductive hormones. METHODS: We collected the clinical data on 134 men complaining of low or decreased sexual desire at our clinic of andrology from January 2013 to July 2018. According to the scores on the 13-item Self-Rating Libido Scale for Males (SRLS-M), we divided the subjects into a low libido (n = 68) and a normal libido group (n = 66), none with thyroid and adrenal diseases, liver and kidney diseases, or administration of drugs affecting sexual function and reproductive hormones in the past two weeks. We compared the age, history and course of disease, SRLS-M scores, levels of serum T, E2, LH, FSH and PRL, and T/E2 ratio between the two groups, and analyzed the correlation of the parameters obtained with the SRLS-M scores of the patients by Pearson correlation analysis. RESULTS: Compared with the males of the normal libido group, the low-libido patients showed a significantly longer course of disease (ï¼»1.83 ± 0.44ï¼½ vs ï¼»2.91 ± 0.08ï¼½ yr, P < 0.05), but lower SRLS-M score (31.47 ± 1.28 vs 19.56 ± 0.89, P < 0.01), T level (ï¼»17.51 ± 3.68ï¼½ vs ï¼»11.46 ± 1.62ï¼½ nmol/L, P < 0.01) and T/E2 ratio (17.27 ± 3.94 vs 12.42 ± 1.38, P < 0.01). No statistically significant differences were found between the normal and low libido groups in age (ï¼»32.22 ± 2.29ï¼½ vs ï¼»31.98 ± 2.19ï¼½ yr) or the levels of E2 (ï¼»103.97 ± 15.70ï¼½ vs ï¼»94.45 ± 10.37ï¼½ pmol/L), FSH (ï¼»9.98 ± 5.26ï¼½ vs ï¼»7.43 ± 3.84ï¼½ IU/L), LH (ï¼»5.70 ± 3.17ï¼½ vs ï¼»5.20 ± 3.37ï¼½ IU/L), or PRL (ï¼»281.96 ± 82.68ï¼½ vs ï¼»371.85 ± 243.38ï¼½ mIU/L). Pearson correlation analysis showed that the SRLS-M scores of the patients in the normal and low libido groups were positively correlated with the T level (r = 0.329 and 0.535, P<0.01) and T/E2 ratio (r = 0.542 and 0.603, P<0.01), and so was the T level with E2 (r = 0.743 and 0.644, P<0.01) and T/E2 (r = 0.387 and 0.618, P<0.01). The areas under the ROC curves for T, E2 and T/E2 were 0.660, 0.527 and 0.669, respectively. A T/E2 ratio of 12.15ï¼15.73 exhibited a relatively high sensitivity (>0.5) and specificity (>0.5) in the diagnosis of low libido. CONCLUSIONS: The T level and T/E2 ratio are important factors, and E2 may also be a factor, influencing male libido, which, however, is more correlated with T/E2. A T/E2 ratio of 12.15ï¼15.73 may be an indicator of normal libido, while a lower or higher T/E2 ratio may suggests low libido.