Observation of the Effects of Extended Comfort Nursing on Cancer-Related Fatigue in Patients with Lung Cancer Undergoing Chemotherapy.

Objective: This study aimed to evaluate the clinical effects of providing extended comfort care to lung cancer patients undergoing chemotherapy and its impact on cancer-related fatigue levels. Methods: Using a retrospective data analysis approach, a total of 88 lung cancer patients receiving chemotherapy at our hospital from March 2021 to March 2022 were selected as research participants. They were divided into an observation group and a control group based on different nursing methods, with 44 patients in each group. The observation group received extended comfort nursing interventions, while the control group received routine nursing care. Patients' comfort levels in both groups were compared, and changes in cancer-related fatigue, self-efficacy, psychological state, coping style, sleep quality, and overall life quality were assessed. Results: Following the nursing interventions, patients in the observation group exhibited better physical, psychological, spiritual, sociocultural, and environmental well-being compared to the control group (P < .05). The observation group also showed lower scores for emotional exhaustion, physical exhaustion, cognitive exhaustion, and overall exhaustion compared to the control group (P < .05). Moreover, patients in the observation group demonstrated higher levels of self-efficacy on the health promotion strategy questionnaire (Supph) (P < .05) and lower scores on the self-rating anxiety and depressive symptoms scales (P < .05) after receiving nursing care. In terms of coping style, patients in the observation group exhibited lower avoidance and yield scores but higher face scores than the control group (P < .05). The observation group also reported higher overall life quality scale item grades (P < .05) and lower Pittsburgh Sleep Quality Index (PSQI) scores (P < .05) compared to the control group. Conclusions: Extended comfort care for lung cancer patients during chemotherapy improves emotional and physical comfort and effectively reduces cancer-related fatigue levels. These findings have significant implications for clinical practice.

Structural Characterization, Simulated Digestion and Anti-Aging Activities of an Acidic Polysaccharide from Salvia Miltiorrhiza.

An acidic polysaccharide (SMP) with a molecular weight (Mw) of 1.28 × 106 Da was isolated from Salvia miltiorrhiza. The monosaccharide composition in molar percentages was rhamnose (Rha): galacturonic acid (GalA): galactose (Gal): arabinose (Ara) = 6.15: 55.98: 21.27: 16.69. The results of simulated digestion in vitro showed that SMP was not degraded in saliva, gastric juice or intestinal juice. The Y maze test and new object recognition test showed that SMP could improve the working memory impairment of aging mice. SMP could also increase the activity of superoxide dismutase (SOD) and catalase (CAT) in serum and brain tissue, decrease the content of malondialdehyde (MDA), decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue, and increase the content of short-chain fatty acids (SCFA) in the intestine. In addition, SMP could also regulate the intestinal flora structure, including increasing the relative abundance of Firmicutes and Bacteroidetes and decreasing the relative abundance of Proteobacteria. This work lays a foundation for the development of functional foods related to Salvia miltiorrhiza.

Stromal cell-derived factor-1 promotes osteoblastic differentiation of human bone marrow mesenchymal stem cells via the lncRNA-H19/miR-214-5p/BMP2 axis.

BACKGROUND: Stromal cell-derived factor-1 (SDF-1) plays an important role in the osteoblastic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs), but the specific mechanism remains unclear. Our study aimed to clarify the role of the lncRNA-H19/miR-214-5p/BMP2 axis in the osteoblastic differentiation of hBMMSCs induced by SDF-1. METHODS: We used reverse-transcriptase polymerase chain reaction, western blotting, alkaline phosphatase activity test, and Alizarin red staining to evaluate the osteoblastic differentiation of primary hBMMSCs and the luciferase reporter assay to determine if lncRNA-H19 binds with miR-214-5p. RESULTS: Our results indicated that SDF-1 (50 ng/mL) promotes the osteoblastic differentiation of hBMMSCs, significantly upregulates osteoblastogenic genes (OCN, OSX, RUNX2, and ALP), and increases Alizarin red staining, alkaline phosphatase activity, and lncRNA-H19 expression. Luciferase reporter assay verified that lncRNA-H19 binds with and represses miR-214-5p, thereby upregulating BMP2 expression. Use of miR-214-5p inhibitor or overexpression of lncRNA-H19 can promote the osteoblastic differentiation of hBMMSCs, but miR-214-5p or shH19 inhibits the osteoblastic differentiation of hBMMSCs. Treatment with an miR-214-5p inhibitor could rescue the inhibitory effect of shH19 on the osteoblastic differentiation of hBMMSCs. CONCLUSIONS: Taken together, SDF-1 promotes the osteoblastic differentiation of hBMMSCs through the lncRNA-H19/miR-214-5p/BMP2 axis. Increased osteoblastic differentiation by an miR-214-5p inhibitor reveals a new possible strategy for the treatment of bone defect and osteoporosis.

Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids.

(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.

A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer.

BACKGROUND: Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. METHODS: Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. RESULTS: Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. CONCLUSIONS: We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals.

BACKGROUND: Treatment of patients coinfected with hepatitis C and human immunodeficiency viruses (HCV; HIV) requires careful consideration of potential drug-drug interactions between HCV direct-acting antiviral agents (DAA) and HIV antiretrovirals. Glecaprevir/pibrentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and an NS5A inhibitor approved for the treatment of chronic HCV genotype 1-6 infection, including patients with HIV coinfection. METHODS: A series of phase 1 studies was conducted to evaluate potential interactions of glecaprevir and pibrentasvir with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, abacavir/dolutegravir/lamivudine, raltegravir, rilpivirine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or efavirenz/emtricitabine/tenofovir disoproxil fumarate. Pharmacokinetics of the antiretrovirals and DAAs were characterized when administered alone and in combination to quantify changes in systemic drug exposure. RESULTS: Glecaprevir area under the curve increased >4-fold in the presence of ritonavir-boosted HIV protease inhibitors, while pibrentasvir concentrations were not significantly affected; elevations in alanine transaminase occurred in combination with atazanavir/ritonavir only. Exposures of glecaprevir and pibrentasvir may be significantly decreased by efavirenz. Coadministration with glecaprevir and pibrentasvir did not result in clinically significant changes in the exposure of any antiretroviral agents. CONCLUSIONS: Atazanavir is contraindicated with glecaprevir/pibrentasvir and use of boosted protease inhibitors or efavirenz is not recommended. No clinically significant interactions were observed with other studied antiretrovirals.

A phase 1 study evaluating safety and pharmacokinetics of losatuxizumab vedotin (ABBV-221), an anti-EGFR antibody-drug conjugate carrying monomethyl auristatin E, in patients with solid tumors likely to overexpress EGFR.

Losatuxizumab vedotin (formerly ABBV-221) is a second-generation antibody-drug conjugate targeting epidermal growth factor receptor (EGFR). In this multicenter phase 1 study, eligible patients with EGFR-dependent solid tumors received losatuxizumab vedotin (3 + 3 design) intravenously at starting dose of 0.3 mg/kg over 3 h per 21-day cycle, with alternate dosing schedules utilized (2 weeks on/1 week off or weekly) to mitigate infusion reactions. Forty-five patients received ≥1 doses of losatuxizumab vedotin (13 colon, 6 non-small cell lung cancer, 5 head and neck [HNC], 5 glioblastoma multiforme, 2 breast, 14 other). Tumor samples were evaluated for EGFR protein expression by immunohistochemistry, EGFR and EGFR ligand mRNA expression by RNAseq, and results compared with outcome. Most common adverse events were infusion-related reaction (22/45; 49%) and fatigue (20/45; 44%). While most infusion reactions were grade ≤ 2, four patients experienced grade ≥3 infusion reactions. Several infusion reaction mitigation strategies were explored. Because of the high incidence of infusion reactions, the trial was stopped and the maximum tolerated dose was not reached. The last cleared dose: 6 mg/kg/cycle. Nineteen patients (42%) had stable disease; 4 remained on study >6 months. One HNC patient with increased levels of EGFR and EGFR ligands (amphiregulin, epiregulin) achieved a confirmed partial response. Pharmacokinetic analysis of losatuxizumab vedotin showed exposures appeared to be approximately dose-proportional. The high frequency of infusion reactions necessitated early closure of this trial. The detailed mitigation strategies used in this protocol for infusion-related reactions may provide beneficial information for trial design of agents with high infusion reaction rates.

New model of the fiber coupling efficiency of a partially coherent Gaussian beam in an ocean to fiber link.

The fiber coupling efficiency between the turbulent ocean to fiber of a partially coherent Gaussian beam propagating through the weak to strong anisotropic oceanic turbulence is studied. We derive the expression of new model of the fiber coupling efficiency for the partially coherent Gaussian beam. The numerical analyses reveal that larger inner scale and anisotropic factor, weaker oceanic turbulence strength, and smaller temperature-salinity contribution ratio will lead to a higher coupling efficiency; a longer wavelength, an suitable aperture diameter of the coupling lens, an optimum focal length and beam size, and a higher coherent degree will improve the fiber coupling efficiency. Our fiber coupling efficiency is higher than the previous fiber coupling efficiency.

Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics.

PURPOSE: Venetoclax is a selective BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). It is predominately metabolized by cytochrome P450 (CYP) 3A. The study objective was to determine the effect of different dosage regimens of ritonavir, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax in 20 healthy subjects. METHODS: In cohorts 1 and 2, subjects received single 10 mg doses of venetoclax in periods 1 and 2 and a single 50- or 100-mg dose of ritonavir in period 2. In cohort 3, subjects received 10-mg venetoclax doses on day 1 of period 1 and days 1 and 11 of period 2, and 50 mg ritonavir daily on days 1 to 14 of period 2. RESULTS: Single doses of 50 and 100 mg ritonavir increased the venetoclax maximum concentration (Cmax) 2.3- to 2.4-fold compared to venetoclax alone and the area under the curve (AUC) 6.1- and 8.1-fold, respectively. Daily 50 mg ritonavir resulted in a 2.4- and 7.9-fold increase in venetoclax Cmax and AUC, respectively. Administration of 50 mg ritonavir daily saturated CYP3A inhibition and completely inhibited the formation of the major venetoclax metabolite M27. Time-dependent CYP3A inhibition with daily 50 mg ritonavir was offset by ritonavir CYP3A induction, resulting in a limited net increase in CYP3A inhibition with multiple doses. CONCLUSION: After completion of the dose ramp-up, venetoclax dose reductions of at least 75% are recommended when administered concomitantly with strong CYP3A inhibitors to maintain venetoclax exposures within the established therapeutic window for CLL treatment.

Fiber coupling efficiency of Gaussian-Schell model beams in an ocean to fiber link with a Zernike tilt correction.

The fiber coupling efficiency of Gaussian-Schell model beams propagating through the oceanic turbulence of the Zernike tilt correction is studied. We derive the expression of the Zernike tilt corrected wave structure function. The numerical analysis reveals that a higher correction factor and spatial coherence of the laser beam increase the fiber coupling efficiency of the link. Our work shows that the increment of the fiber coupling efficiency caused by Zernike tilt correction under strong turbulence conditions is stronger than in the weak turbulence conditions, and the salinity fluctuation has a greater impact on it than temperature fluctuation does.