Preparation and cytotoxicity of doxorubicin-containing gold nanoparticles / 药学实践杂志

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.

Research progress on clinical application and quality control of sprays / 药学实践杂志

Sprays have gained significant attention and widespread use due to their numerous advantages, including rapid action, safety, and convenience. They are widely used in various fields such as dermatology, respiratory disease treatment, wound repair, and central nervous system targeted drug delivery. With the in-depth research of new drugs and modern pharmaceutics, the development ideas of sprays are more diverse, and the application scenarios are increasingly extensive. In this review the clinical application status of sprays and the latest research progress were summarized. Then the quality control parameters were briefly introduced，which provided reference for the research and development of sprays.

Content measurement of doxorubicin hydrochloride and lonidamine by HPLC / 药学实践杂志

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Preparation and pharmacokinetics of flumazenil sublingual tablet / 药学实践杂志

Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml−1, respectively; Cmax was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; tmax was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.

Front-line therapy for brain metastases and non-brain metastases in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: a network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses.@*METHODS@#Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework.@*RESULTS@#This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively.@*CONCLUSION@#Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.

Dynamic nonlinearity errors in laser Doppler vibrometer measurements induced by environmental vibration and error correction.

Laser Doppler vibrometers (LDVs) are widely used for vibration testing in various fields. Nonlinearity errors are the key factor affecting the measurement accuracy of LDVs. The conventional Heydemann method cannot correct nonlinearity errors produced by noisy environments. Thus, we establish a novel model to describe dynamic nonlinearity errors produced in noisy environments and propose a compensation method to mitigate signal distortion. The performance of the proposed method is assessed by performing both simulations and experiments. The results of experiments carried out in a noisy environment indicate that the proposed method suppresses the nonlinearity to 30 nm compared to 737 nm using the conventional Heydemann correction. The proposed method can improve the accuracy of LDV measurements in industrial environments.

Review on the Combination Strategy of Anti-angiogenic Agents and Other Anti-tumor Agents in Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Treatments for advanced non-small cell lung cancer (NSCLC) include chemotherapy, targeted therapy, and immunotherapy represented by immune checkpoint inhibitors. However, the efficacy of monotherapy is still limited. Nowdays, combination strategy has drawn great attention. Anti-angiogenic agents are widely used in treating advanced NSCLC, which can not only suppress the growth and metastasis of tumor by suppressing tumor vessels, and also have synergic effect with other anti-tumor agents because they can normalize vessels and regulate immune micro-environment. This article summarizes the underlying mechanism of combining anti-angiogenic agents and other anti-tumor agents, reviews the clinical trials on the combination strategy including monoclonal antibodies and tyrosine kinase inhibitor, so as to provide a potential strategy for treating advanced NSCLC.
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Thoracic aortic computed tomography angiography in swine: establishment of a baseline for endovascular evaluation of the ascending aorta.

OBJECTIVES: Our goal was to establish a baseline of computed tomography (CT) angiographic data for the porcine ascending thoracic aorta for endovascular evaluation of animal experiments and device development. METHODS: Thoracic aortic CT angiography was conducted on 49 pigs with an average body weight of 60-65 kg. The CT angiographic scans were done on an imaging reconstruction workstation to obtain the specific aortic geometric data, including the diameters of the planes, the heights among the planes and the clock positions of target arteries. RESULTS: Fourteen important planes were defined in the study for endograft customizing reference. The diameters of the planes were measured, and the heights among the planes were recorded. For endograft fenestrations, the right coronary artery ostium clock position was 100.11 ± 7.29°, and the brachiocephalic trunk ostium clock position was 74.72 ± 6.45°. The best projection angle of the tangent position of the left coronary artery was the right anterior oblique 17 ± 7° position. A pig with a rare congenital giant dilated aorta was found among the candidate experimental animals. CONCLUSIONS: For experimental porcine models, CT angiography has proved to be a suitable imaging technique. The established baseline angiography of the swine can provide reference values for future animal experiments and device development.

Dynamics of partially obstructed breakup of bubbles in microfluidic Y-junctions.

For revealing the dynamics of partially obstructed breakup of bubbles in microfluidic Y-junctions, the combination of dimensionless power-law and geometric model was applied to study the effects of capillary number, bubble length, and channel angle on the bubble rupture process. In the squeezing process, the gas-liquid interface curve follows the parabolic model. For the evolution of the bubble neck during breakup, the increase of the bubble length, the channel angle, and the capillary number leads to the decrease of the focus distance α. The chord m increases with the increase of the capillary number and the decrease of the bubble length, and it would reach the maximum value when the channel angle is 90°. In the fast pinch-off stage during bubble breakup, the bubble's neck curve no longer conforms to the parabolic model so the focus and chord no longer exist. For the evolution of the bubble head during breakup, the value of γ approaches 1 with the increase of the capillary number and the bubble length, and with the close of the channel angle to 90°. It is found that the quadrilateral model can be applied for the partially obstructed rupture of bubbles in the symmetrical microfluidic Y-junction.

Review on Treatment Modalities for Resectable IIIa/N2 Non-small Cell Lung Cancer / 中国肺癌杂志

Standard treatment for resectable IIIa/N2 non-small-cell lung cancer (NSCLC) is still under debate. Optional treatments include chemotherapy, radiotherapy and surgery, other options include target therapy and immunotherapy. Multidisciplinary treatment has therefore been emphasized by various clinical trials, including bimodality strategy which has been defined as chemotherapy plus surgery or chemotherapy plus radiotherapy, and trimodality treatment which refers to chemotherapy plus surgery and radiotherapy. However, there is still no consensus on the optimal strategy on treating resectable IIIa/N2 NSCLC. Therefore, we reviewed a series of phase II and III clinical trials as well as some meta-analyses and case reports to compare the efficacy of different strategies on survival of cN2 NSCLC, and concluded that for resectable IIIa/N2 NSCLC surgery is recommended, and that strategy of chemotherapy plus surgery may not achieve better survival than that of chemotherapy plus radiotherapy. Size of tumor as well as lymph nodes should be taken into account when choosing optimal therapy, so that promising individualized strategy could be given to patients with resectable stage IIIa/N2 NSCLC.
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Neuropeptide Y stimulates osteoblastic differentiation of murine MC3T3-E1 cells related to activated Wnt signaling in vitro / 中华创伤骨科杂志

Objective To investigate the effect of neuropeptide Y (NPY) on the osteoblastic differentiation of murine MC3T3-E1 cells and its mechanism related to the Wnt signaling pathway.Methods The murine MC3T3-E1 cells were divided into 4 groups according to the stimulators added:phosphate buffered saline (PBS) (control) and different concentrations of NPY (10-8 mol/L,10-10 mol/L and 10-12 mol/L).The cellular proliferation was detected with MTT assay after 1,3,5,7 and 9 days.The cells were identified with cell immunochemistry and Western Blot to find out the most effective concentration of NPY at different time points under osteoblastic condition.The cells were then divided into 4 groups:PBS,NPY,NPY + NPY receptor antagonist,and NPY + DKK1.Western blot was used to determine the expression of β3-catenin and p-GSK-3β in each group.Nuclear signaling activity of β3-catenin was observed using immunofluorescence staining.Results NPY significantly improved the proliferation of MC3T3-E1 cells at 7 and 9 days (P ＜0.05).NPY (10s mol/L and 10-10 mol/L) groups and NPY (10-10 mol/L and 10-12 mol/L) groups significantly improved the ALP activity at 4 and 14 days respectively (P ＜ 0.05).At 4 days,the expression of ALP protein was significantly decreased in the NPY + DKK1 group and the NPY + NPY receptor antagonist group compared with that in the NPY group (P ＜ 0.05).Although the expression levels of [β-catenin and p-GSK-3β protein were uninfluenced in either case,NPY significantly stimulated the nuclear signaling activity of β3-catenin.Conclusions NPY may significantly increase the expression of ALP protein in MC3T3-E1 ceils during osteoblastic differentiation.This effect might be mediated through the canonical Wnt signaling pathway.