An Observational Study on the Application of the Second-generation Radiopaque Subcutaneous Implant.

To analyze the effect, side effects, and satisfaction of the second-generation radiopaque subcutaneous implant, providing healthcare workers a basis for propaganda and guidance. Methods: A total of 214 cases of healthy women with birth control requirements from August 2016 to June 2018 received ray subcutaneous implants. Quantitative surveys were administered 10 days, 3 months, 12 months, and 24 months later. All cases were implanted successfully. The number of effective cases was 211, with 3 cases lost to follow-up. The pregnancy rate of 211 subjects during receiving implant was 0. Changes in bleeding patterns (130 cases, 61.61%) remained the most common side effect event. The rate of withdrawal was 96.21% in the first year and 66.35% in the second year. There were 48 cases (67.61%) who withdrew due to the change of bleeding pattern. All participants with bleeding patterns were divided into the withdrawal group and the non-withdrawal group, and there were significant differences in educational background, number of pregnancies, abortion, and income between the two groups. According to the satisfaction survey, 37 (17.54%) were very satisfied, 109 (51.66%) were satisfied. The contraceptive rate of radiopaque subcutaneous implantation was very high, and there were no serious side effects while receiving an implant. The change of bleeding pattern was the main reason for withdrawal, which was related to educational background, number of pregnancies, history of abortion, and economic conditions. Pre-implantation consultation and post-implantation management should be strengthened.

SNP rs12794714 of CYP2R1 is associated with serum vitamin D levels and recurrent spontaneous abortion (RSA): a case-control study.

PURPOSE: Vitamin D (VD) deficiency seems to be associated with the risk of recurrent spontaneous abortion (RSA). Vitamin D receptor (VDR) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) are two genes which are vital for VD metabolism and actions. However, whether single-nucleotide polymorphisms (SNPs) in these genes are correlated with the risk of RSA are poorly understood. Therefore, we aimed to characterize the relationships among VDR SNPs, CYP2R1 SNPs and RSA. METHODS: This case-control study enrolled 75 RSA patients and 83 controls. Serum VD and some cytokines were detected with LC-MS/MS and flow cytometry, respectively. Genotyping for three SNPs of CYP2R1 (rs10741657, rs10766197 and rs12794714) and five SNPs of VDR (rs7975232, rs1544410, rs2189480, rs2228570 and rs2239179) was done with polymerase chain reaction (PCR) and high-throughput sequencing. All the data were analyzed with appropriate methods and in different models. RESULTS: The results revealed a significant correlation between the AG genotype of CYP2R1 rs12794714 and VD levels (OR 0.686; 95% CI 0.49-0.96; p = 0.028). Besides, the AG and GG genotypes of CYP2R1 rs12794714 were markedly related to the risk of RSA (OR 52.394, 59.497; 95% CI 2.683-1023.265, 3.110-1138.367; p = 0.009, 0.007, respectively). CONCLUSION: Our results indicate that CYP2R1 rs12794714 might be a risk factor for RSA. Hence, early screening of pregnant women for CYP2R1 rs12794714 is necessary to warrant proactive counseling and treatment against RSA.

Rational Combination Therapy for Melanoma with Dinaciclib by Targeting BAK-Dependent Cell Death.

Mutation of the oncogene BRAF is among the most common genetic alterations in melanoma. BRAF inhibitors alone or in combination with MEK inhibitors fail to eradicate the tumor in most patients due to combinations of intrinsic or acquired resistance. Therefore, novel strategies are needed to improve the therapeutic efficacy of BRAF inhibition. We demonstrated that dinaciclib has potent antimelanoma effects by inducing BAK-dependent apoptosis through MCL1 reduction. Contrary to dinaciclib, the inhibitors of BRAF/MEK/CDK4/6 induced apoptosis dominantly through a BAX-dependent mechanism. Although the combination of BRAF and MEK inhibitors did not exhibit additive antimelanoma effects, their combination with dinaciclib synergistically inhibited melanoma growth both in vitro and in vivo Collectively, our present findings suggest dinaciclib to be an effective complementary drug of BAX-dependent antimelanoma drugs by targeting BAK-mediated apoptosis, and other such rational drug combinations can be determined by identifying complementary drugs activating either BAK or BAX.

[Impact of cigarette smoking on sperm quality and seminal plasma ROS in preconception males].

OBJECTIVE: To investigate the influence of cigarette smoking on sperm quality and ROS in the seminal plasma of preconception males in Chongqing so as to provide some guidance for preconception couples. METHODS: Totally, 368 preconception males were enrolled in this study, including 196 smokers and 172 non-smokers, and the former divided into mild smokers (n = 88, ≤9 cigarettes per day for ≤5 years) and moderate to heavy smokers (n = 108, ≥10 cigarettes per day for ≥5 years or ≤9 cigarettes per day for ≥10 years). All the subjects underwent physical examination, medical history interview, health questionnaire investigation, and determination of semen parameters, ROS in the seminal plasma and sperm DNA fragmentation index (DFI). RESULTS: Among the 368 preconception males, 53.26% had a history of cigarette smoking, of whom 29.35% were moderate to heavy smokers. Only 55.4% of the subjects were found with normal sperm morphology and 52.6% with normal sperm progressive motility. Compared with the non-smokers, the moderate to heavy smokers showed significantly decreased semen volume (ï¼»3.33 ± 1.20ï¼½ vs ï¼»2.78 ± 1.08ï¼½ ml, P < 0.05), sperm concentration (ï¼»88.19 ± 70.33ï¼½ vs ï¼»75.16 ± 60.13ï¼½ × 106/ml, P < 0.05), and percentages of progressively motile sperm (PMS, ï¼»36.58 ± 13.90ï¼½ % vs ï¼»32.18 ± 15.24ï¼½ %, P < 0.05) and morphologically normal sperm (MNS, ï¼»3.85 ± 1.93ï¼½ % vs ï¼»3.52 ± 1.58ï¼½ %, P < 0.05), but increased sperm DFI (ï¼»10.45 ± 8.53ï¼½ % vs ï¼»14.53 ± 12.85ï¼½ %, P < 0.05) and ROS in the seminal plasma (ï¼»12.20 ± 8.10ï¼½ vs ï¼»24.10 ± 18.50ï¼½ nmol/mg prot, P < 0.05). Cigarette smoking was correlated positively with the ROS level in the seminal plasma (r = 0.235, P < 0.05), while the ROS level of the smokers negatively with the total sperm count (r = －136, P < 0.05), PMS (r = －0.381, P < 0.01) and MNS (r = －0.218, P < 0.01), but positively with sperm DFI in the preconception males (r = 0.387, P < 0.01). CONCLUSIONS: Cigarette smoking can increase the ROS level in the seminal plasma, decrease the total sperm count and sperm progressive motility, and induce sperm malformation and sperm DNA fragmentation in preconception males.

Coptidis Rhizoma induces intrinsic apoptosis through BAX and BAK activation in human melanoma.

Malignant melanoma has exhibited a rising incidence in recent years worldwide. Although various molecular targeted drugs are being researched and developed for melanoma patients, their efficacy appears to be unsatisfactory. Over the past few years, several reports have demonstrated that Coptidis Rhizoma water extracts (CR) or its major active chemical component, berberine, has anticancer activities in various types of cancer, including melanoma. However, their underlying mechanisms have not been well understood. In the present study, we determined that CR suppressed melanoma cell viability, which was mainly mediated through apoptosis. In addition, the expression levels of anti-apoptotic proteins, BCL2A1, MCL1 and BCL-w, were strongly suppressed by CR treatment. Furthermore, multi-domain pro-apoptotic proteins BAX and BAK were activated by CR treatment and were also required for the CR-induced apoptosis. Collectively, CR or some formulations containing CR, may be effective safe treatment strategies for human melanoma.

Swap70b is required for convergent and extension cell movement during zebrafish gastrulation linking Wnt11 signalling and RhoA effector function.

Swap70 functions as a guanine nucleotide exchange factor for Rac and RhoA regulating F-actin cytoskeletal rearrangements and playing a crucial role in mammalian cell activation, migration, adhesion and invasion. Here we show that the zebrafish orthologue, Swap70b, is required for convergent and extension cell movement during gastrulation. Swap70b morphants exhibited broader and shorter body axis but cell fate specification appeared normal. While ectopic Swap70b expression robustly rescued Wnt11 morphants, RhoA overexpression was sufficient to rescue Swap70b morphants, establishing Swap70b as a novel member of the non-canonical Wnt/PCP pathway downstream of Wnt11 and upstream of RhoA. This is distinct from the related Def6a protein that acts downstream of Wnt5b. Def6a/Swap70b morphants resemble Ppt/Slb double mutant embryos suggesting that Swap70b and Def6a delineate Wnt11 and Wnt5b signalling pathways.