Analysis of the Efficacy of Polyenyl Phosphatidylcholine in Combination with Liraglutide in Nonalcoholic Fatty Liver Disease and the Effect of Omentin-1 and Vaspin Expression.

Objective: To evaluate the efficacy of combining polyene phosphatidylcholine (PPC) with liraglutide in the treatment of nonalcoholic fatty liver disease (NAFLD) and investigate its impact on adipokine expression, specifically omentin-1 and vaspin. Methods: One hundred twenty NAFLD patients were randomly assigned to either the observation group (n = 60) or the control group (n = 60). The control group received single-dose PPC treatment, while the observation group received a combination of PPC and liraglutide for 12 weeks. Clinical efficacy, adipose-related factors (omentin-1, vaspin, serum fibroblast growth factor 21 (FGF21)), liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT)), and adverse reaction rates were compared between the two groups before and after treatment. Results: In the observation group, the clinical effectiveness rate (95.00%) was significantly higher than that in the control group (83.33%) (P < .05). Before treatment, there were no significant differences in omentin-1, vaspin, FGF21, ALT, AST, and GGT between the two groups (P > .05). After treatment, both groups showed decreased levels of vaspin, FGF21, ALT, AST, and GGT, along with increased omentin-1 levels. However, levels of vaspin, FGF21, ALT, AST, and GGT were lower in the observation group compared to the control group, while omentin-1 levels were higher (P < .05). Adverse reaction rates did not significantly differ between the two groups (10.00% vs. 6.67%) (P > .05). Conclusions: The combination therapy of PPC and liraglutide demonstrates efficacy in treating NAFLD, improving adipose-related factors, and reducing liver enzyme activity with high safety. This approach warrants broader clinical implementation.

Microstructure Optimization for Design of Porous Tantalum Scaffolds Based on Mechanical Properties and Permeability.

Porous tantalum (Ta) implants have important clinical application prospects due to their appropriate elastic modulus, and their excellent bone growth and bone conduction ability. However, porous Ta microstructure designs generally mimic titanium (Ti) implants commonly used in the clinic, and there is a lack of research on the influence of the microstructure on the mechanical properties and penetration characteristics, which will greatly affect bone integration performance. This study explored the effects of different microstructure parameters, including the fillet radius of the middle plane and top planes, on the mechanics and permeability properties of porous Ta diamond cells through simulation, and put forward an optimization design with a 0.5 mm midplane fillet radius and 0.3 mm top-plane fillet radius in order to significantly decrease the stress concentration effect and improve permeability. On this basis, the porous Ta structures were prepared by Laser Powder Bed Fusion (LPBF) technology and evaluated before and after microstructural optimization. The elastic modulus and the yield strength were increased by 2.31% and 10.39%, respectively. At the same time, the permeability of the optimized structure was also increased by 8.25%. The optimized microstructure design of porous Ta has important medical application value.

The incidence rate of allergic reactions induced by oxaliplatin is higher in patients with rectal cancer compared with colon cancer.

AIM: To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer. METHODS: From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer. RESULTS: We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients. CONCLUSION: Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

Correlation between pharmacokinetic parameters of 5-fluorouracil and related metabolites and adverse reactions in East-Asian patients with advanced colorectal cancer.

BACKGROUND AND OBJECTIVE: To examine the range of the area under the concentration-time curve (AUC) calculated using plasma 5-FU concentration at steady-state plasma concentration-time of 5-fluorouracil (5-FU) and correlation between 5-FU metabolites (5,6-dihydro-5-fluorouracil, 5-FUH2 and α-fluoro-ß-Alanine, FBAL) plasma concentration and adverse reactions when patients with advanced colorectal cancer (CRC) received 5-FU-based chemotherapy. METHODS: 74 patients with advanced CRC receiving 5-FU-based chemotherapy from Aug. 2017 to Nov. 2020 in Harbin Medical University Cancer Hospital were involved in this study, the dosage of 5-FU being determined according to the patient's body surface area (BSA). Using an ultra-high performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) to determine the 5-FU steady-state plasma concentration (CSS) and plasma concentration of 5-FUH2 and FBAL in CRC patients receiving 5-FU in continuous intravenous infusion for 18-30 h, the start time and end time of 5-FU infusion in patients were accurately recorded and the continuous infusion time (TCI) was calculated. The AUC value was calculated according to AUC = CSS × TCI. At the same time, the treatment effects and adverse drug reactions of patients were evaluated, to analyze the relationship between 5-FU AUC, 5-FUH2 and FBAL plasma concentration and clinical efficacy and adverse reactions in CRC patients, and explore the ideal AUC range of 5-FU in the treatment of colorectal cancer. RESULTS: The AUC of 5-FU was not normally distributed and ranged from 3.13 to 41.12mgh/L, with an average value of 14.81 ± 8.62 mg·h /L, and the AUC values had obvious inter-individual differences up to 13 times. 5-FUH2 ranged from 131.98 to 987.93 ng/mL, with an average of 550.58 ± 260.60 ng/mL; FBAL ranged from 23.58 to 262.48 ng/mL, with an average of 89.79 ± 58.47 ng/mL. Correlation analysis results revealed a significant correlation between 5-FU AUC, 5-FUH2 and FABL plasma concentration and adverse reactions, 5-FU AUC and clinical efficacy. CONCLUSIONS: There are obvious individual differences in AUC values in CRC patients receiving different dosages of 5-FU based on BSA. The ideal AUC range of 5-FU is 18.23-29.17 mg·h/L. There was a significant correlation between 5-FUH2 and FABL plasma concentration and adverse reactions.

Incidence risk of PD-1/PD-L1-related pneumonia and diarrhea in non-small cell lung cancer (NSCLC) patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Programmed cell death-1 (PD-1) and programmed cell death ligand-1(PD-L1) inhibitor therapy have been approved for the treatment of many cancers, although their incidence of some side effects was high. We aim to fully investigate the incidence risk of PD-1/PD-L1 inhibitors-related pneumonia and diarrhea in NSCLC patients, as well as treatment-related deaths. METHODS: PubMed, Medline, Cochrane Library, and Clinical trials.gov databases were searched up to Sep 17, 2020, for clinical trials of PD-1 inhibitors and PD-L1 inhibitors in the treatment of NSCLC. Randomized controlled trials and their references were screened. RESULTS: Seventeen trials were included in our meta-analysis, including 11,363 patients. PD-1/PD-L1 inhibitors significantly increased the risk of developing all-grade and high-grade (grade ≥ 3) pneumonia (risk ratio [RR] = 2.28; 95% CI: 1.39-3.76; P < 0.01; RR = 2.38; 95% CI: 1.72-3.29; P < 0.01, respectively). The use of PD-1/PD-L1 inhibitor did not increase the risk of developing all-grade and high-grade diarrhea (RR = 0.79; 95% CI: 0.62-1.01; P = 0.06; RR = 0.96; 95% CI: 0.70-1.31; P = 0.78, respectively). There was no significant difference between the rate of death in PD-1 and PD-L1 inhibitors (P = 0.079). CONCLUSION: These data suggest that PD-1/PD-L1 inhibitors significantly increase the risk of all-grade and high-grade pneumonia in NSCLC patients and PD-1/PD-L1 monotherapy increases the risk of all-grade pneumonia in NSCLC patients compared to PD-1/PD-L1 inhibitor combination regimens. Physicians should pay more attention to NSCLC patients who treated with PD-1/PD-L1 inhibitors.

CDA and MTHFR polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine-based chemotherapy.

PURPOSE: The impact of pharmacogenetics on predicting survival in gastroenteric cancer remains unclear. METHODS: We tested 322 consecutive patients treated with capecitabine-based chemotherapy for CDA and MTHFR polymorphisms. RESULTS: Patients who carried the CDA 79 A>C (rs2072671) CC genotype showed significantly shorter progression-free survival (PFS) comparing with A-allele (P = 0.008). A significant better PFS was found in the patients with 451 A>G (rs532545) G-allele (P = 0.002) and 92 C>T (rs602950) T-allele (P = 0.002). In addition, a shorter PFS was also observed in patients with MTHFR 1298 A>C (rs1801131) CC genotype than the patients with AC or AA genotype after capecitabine-based chemotherapy (P = 0.002). Furthermore, the colon, female, or elder (> 65 years old) patients with MTHFR 1298 A>C CC genotype had poorer PFS than A-allele. Moreover, CDA 451 A>G was independent predictors of chemotherapy-induced toxicity in colon patients. Multivariate Cox regression analysis demonstrated that the CDA 79 A>C CC, 451 A>G AA, 92 C>T CC, and MTHFR 1298 A>C CC were predictive of shorter PFS in gastroenteric cancer patients. CONCLUSIONS: The results reminded us those gastroenteric cancer patients with CDA 79 A>C CC, 451 A>G AA, 92 C>T CC, or MTHFR 1298 A>C CC genotype are not likely to benefit from the therapy of capecitabine-based chemotherapy.

A Nitrogen-Doped Manganese Oxide Nanoparticles/Porous Carbon Nanosheets Hybrid Material: A High-Performance Anode for Lithium Ion Batteries.

A nitrogen-doped MnO nanoparticles/ porous carbon nanosheets (N-MnO/PCS) composite was synthesized by the room-temperature redox reaction between KMnO4 and PCS followed by a facile carbothermal reduction, and a subsequent coating process of urea onto MnO/PCS and heat treatment. N-MnO nanoparticles with a grain size of about 30 nm are homogenously embedded on the surface of the N-PCS, corresponding to a high loading of 50.09 wt.% in the resulting composite. Benefiting from the enhanced reaction kinetics as well as electrical conductivity and continuous transport pathways of Li+ /electron resulting from the N-doping and hybridization of the cross-linked porous carbon substrate, the as-synthesized N-MnO/PCS-1 electrode delivers a large reversible specific capacity (1497.2 mA h g-1 at 100 mA g-1 after 160 cycles), outstanding rate capacities (710.6 mA h g-1 at 1 A g-1 and 640.1 mA h g-1 at 2 A g-1 ) and long-term cycling stability with specific capacity (976 mA h g-1 at 0.5 A g-1 after cycling 300 cycles). The simple and green synthesis and electronic properties of this composite mean that it has great potential as a high-capacity anode material for practical application in large-scale energy storage devices.