Abstract Objective: To study the effects of single-nucleotide polymorphisms of the OPRM1 and ABCB1 genes on the analgesic effect and consumption of sufentanil after thoracoscopic-assisted radical resection of lung cancer. Methods: A total of 225 Chinese Han nationality patients undergoing thoracoscopic-assisted radical resection of lung cancer were enrolled in the present study. Among them, 132 were males (58.67%) and 93 (41.33%) were females having American Society of Anesthesiologists statuses classified as grades I or II. The rs1799971, rs563649 and rs1323040 genotypes of the OPRM1 gene and rs2032582, rs1045642 and rs1128503 genotypes of the ABCB1 gene were detected by Sanger sequencing. The state anxiety index and pressure pain threshold were assessed preoperatively. Sufentanil was administered intravenously to maintain anesthesia. The doses and side effects of sufentanil consumed 6 h (T1), 24 h (T2) and 48 h (T3) after surgery were recorded. Results: The sufentanil doses at T1, T2 and T3 were significantly higher in radical-operation lung cancer patients with mutant homozygous rs1799971 and rs1323040 loci in the OPRM1 gene and rs2032582 and rs1128503 loci in the ABCB1 gene. The doses of sufentanil consumed by mutant heterozygous lung cancer patients at T1, T2 and T3 were significantly higher than those consumed by patients without mutations, and the differences were statistically significant (P<0.05). There was no significant difference in sufentanil doses consumed by lung cancer patients with mutant homozygous, mutant heterozygous and wild-type rs563649 locus of the OPRM1 gene and rs1045642 locus of the ABCB1 gene at T1, T2 and T3 (P>0.05). There was no significant difference in the visual analog scale scores at T1, T2 and T3 for different genotypes of OPRM1 and ABCB1 genes in lung cancer patients (P>0.05). No significant difference was found between the adverse reactions of OPRM1 and ABCB1 genotypes in patients undergoing radical resection of lung cancer (P>0.05). Conclusion: The rs1799971 and rs1323040 polymorphisms of the OPRM1 gene and rs2032582 and rs1128503 polymorphisms of the ABCB1 gene are related to the analgesic effect and consumed dose of sufentanil in Chinese Han patients undergoing radical operation of lung cancer.
INTRODUCTION Helicobacter (H.) hepaticus infection causes chronic active hepatitis and induces hepatocellular tumours in A/JCr mice, but evidence of this in humans is scarce.This study aimed to demonstrate the correlation between H. hepaticus and human primary hepatocellular carcinoma (HCC). MeThODsThe sera of 50 patients with primary HCC were tested for the presence of anti-H.pylori and anti-H.hepaticus immunoglobulin G (IgG) antibodies.The liver tissues of patients who tested positive for serum antibody were analysed for H. hepaticus-specific 16S rRNA, H. hepaticus cdtB, H. pylori cagA, H. pylori vacA and H. pylori ureC genes using polymerase chain reaction. ResUlTsAfter the anti-H.pylori antibodies in the serum samples were absorbed by H. pylori antigen, the anti-H.hepaticus IgG serum antibody detection rate was 50.0% in patients with primary HCC.This was significantly higher (p < 0.001) than the detection rate in the benign liver tumour (7.7%) and normal liver tissue (6.3%) groups.Of the 25 primary HCC samples that tested positive for anti-H.hepaticus IgG serum antibody, the H. hepaticus-specific 16S rRNA gene was detected in nine (36.0%) samples.Sequencing showed that the polymerase chain reaction-amplified product exhibited 95.5%-100% homology to the H. hepaticus-specific 16S rRNA gene.Among these nine primary HCC tissue samples, the H. hepaticus cdtB gene was detected in four (44.4%) samples, while no such expression was observed in the benign liver tumour or normal liver tissue groups.CONClUsION The present study identified the presence of H. hepaticus infection in patients with primary HCC using serological and molecular biological detection, suggesting that H. hepaticus infection may be involved in the progression of HCC.
Patients with inflammatory diseases, such as rheumatoid arthritis (RA) frequently continue to suffer from morning symptoms despite treatment with conventional therapies [1,2]. Routine morning administration of tofacitinib results in peak drug concentrations several hours (around 12 noon) after peak cytokine release and disease symptoms. A product designed to be taken at bedtime and exhibiting a delated and extended tofacitinib release profile that releases tofacitinib late in the night providing maximum tofacitinib concentrations in the early morning hours (approximately 4 a.m.), could provide an enhanced opportunity to address morning symptoms.
Objectives:
T19 is a novel, three-dimensionally (3D) printed tablet being developed for delayed- release and extended- release (DR/ER) of tofacitinib engineered to provide peak tofacitinib concentrations concurrent with the circadian rhythm of endogenous cytokine release and disease symptoms in the early morning hours. The current study was designed to characterize the pharmacokinetics of T19 and evaluate the single-dose relative bioavailability of T19 compared to Xeljanz XR® in healthy participants.
Methods:
T19 was manufactured by a 3D printing technology called "Melt Extrusion Deposition" (MED®). A total of 24 participants were enrolled in the Phase I, randomized, open-label, single-dose, three-period, three-sequence crossover study to compare the pharmacokinetics (PK) between T19 and the reference listed drug (LD, Xeljanz XR®). Participants were randomized 1:1:1 to receive two formulations of T19 (Z001101 & Z001091; designed to provide differing degrees of delayed release) or LD in the three sequences. T19 was administered orally at bedtime (approximately 22:00) following a standard dinner at approximately 18:00. Following dinner, the participants remained fasted for 4 hours before the administration of T19. Xeljanz XR® was administered orally in the morning after an overnight fast of at least 10 hours. There was a minimum 4-day washout period between treatments.
Results:
Following administration of T19 and Xeljanz XR®, both formulations of T19 exhibited a delayed time of maximum plasma concentration (Tmax), as expected. Under fasting conditions, the median Tmax was 5.5-6.0 h with a range of 3.0-10.0 h for T19, whereas the median Tmax was 4.5 h (2.5-5.0 h) for the LD. The Tmax of the T19 formulations were significantly different as compared to the LD (Wilcoxon signed-rank test, p <0.001). Other than the delayed drug release (Tmax), the PK profile of T19 was superimposable with the LD, including exhibiting similar PK parameter estimates for drug absorption and elimination. A statistical analysis of relative bioavailability between the formulations demonstrated that the exposure of T19 was similar to that of LD. The area under the concentration-time curve (AUCinf) and maximum plasma concentration (Cmax) of T19 were within the desired bioequivalence range (80% to 125%) relative to LD. The ratio (T19/LD) and 90% confidence intervals of adjusted geometric means for AUCinf and Cmax were 105.46 (102.03, 109.38) and 116.95 (104.92, 130.35) for Z001101, and 104.04 (100.81, 107.38) and 130.89 (113.49, 150.95) for Z001091, respectively. Geometric mean concentration-time profiles of T19 and LD after single-dose administration are shown in Figure 1.
Conclusion:
The PK results demonstrate that T19 achieved the desired product design properties of delayed- and extended-release, as exhibited by the pharmacokinetic profiles and providing peak plasma concentrations in the early morning hours when morning symptoms are most present. The bioequivalence of exposure (AUC) and Cmax observed suggests a potential pharmacokinetic bridge to Xeljanz XR®, providing a basis for a 505(b)(2) application for the indications similar to the LD, Xeljanz® and a potential therapeutic option for the patients with morning symptoms.
REFERENCES:
[1] Ursini F, et al. Pharmaceutics. 2021 Nov 2;13(11):1832. [2] Cutolo M, et al. Ann Rheum Dis. 2008 Jul;67(7):905-8.
A mixed-solvothermal method starting from dithizone as a slow release source was developed for synthesizing ZnxCd1−xSy photocatalysts with high visible light photocatalytic activities. XRD, TEM, SEM, XRF, BET, UV-Vis DR, Raman and PL spectra were employed to characterize the crystal phases, morphologies, chemical compositions and optical properties of the obtained products. Interestingly, the released zinc ions could form nanoparticles on the surface of nanorods and the excessive growth of sulfur could bring some new optical properties. The visible light photocatalytic properties of the products were also evaluated by photocurrent measurements in steady state conditions. The results indicated that ZnxCd1−xSy, especially Cd0.78Zn0.22S0.94, exhibited excellent photocatalytic activities, about 10 times higher than the commercial CdS and about 5 times higher than the typical CdS QDs. As a result, a possible mechanism was proposed to explain the formation of the ZnxCd1−xSycatalysts.
Background: Microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) translocation renal cell carcinoma (RCC) is a rare type of non-clear cell RCC (nccRCC), which is more common in females. Currently, there is no standardized treatment for advanced metastatic microphthalmia translocation RCC (MiT-RCC). The main treatment modalities include surgery, chemotherapy, immunotherapy, anti-vascular endothelial growth factor or vascular endothelial growth factor receptor (VEGFR) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and targeted therapy against the mesenchymal-epithelial transition (MET) factor signaling pathway.
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