Formulation and Characterization of Ethosomes for Transdermal Delivery of Prinsepia Utilis Rogle Seed Oil with Ameliorative Effects against UVB-Induced Skin Damage.

Prinsepia utilis seed oil (PUSO) is a natural medication obtained from Prinsepia utilis Rogle seed, which has been used for the treatment of skin diseases. The study aims to prepare ethosomes with high drug loading as a water-soluble transdermal vehicle to enhance the transdermal delivery of PUSO. PUSO-loaded ethosomes (PEs) were prepared using a cold method, and optimized by an orthogonal experimental design with entrapment efficiency (EE) as the dependent variable. The PEs prepared with the optimized formulation showed good stability, with a spherical shape under transmission electron microscopy (TEM), average particle size of 39.12 ± 0.85 nm, PDI of 0.270 ± 0.01, zeta potential of -11.3 ± 0.24 mV, and EE of 95.93 ± 0.43%. PEs significantly increased the skin deposition of PUSO compared to the PUSO suspension (P < 0.001). Moreover, the optimum formula showed significant ameliorative effects on ultraviolet B (UVB) irradiation-associated macroscopic and histopathological changes in mice skin. Therefore, PEs represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation, with the potential for industrialization.

Optimal response to tislelizumab plus chemotherapy in metastatic triple-negative breast cancer: a case report and literature review.

Metastatic triple-negative breast cancer (mTNBC) has the worst prognosis among breast cancer subtypes. Immune checkpoint inhibitors (ICIs) plus chemotherapy have promising survival benefits. Herein, we report a 51-year-old woman whose metastatic lesions were diagnosed as triple-negative subtype and who received tislelizumab plus eribulin treatment and achieved excellent efficacy. To our knowledge, this study is the first attempt to present tislelizumab in combination with eribulin for mTNBC treatment. New treatments resulting in prolonged survival and durable clinical responses would benefit mTNBC patients. Then, we summarize the possible influencing factors of the interaction between tislelizumab and eribulin.

Efficacy and safety of alectinib in ALK-positive non-small cell lung cancer and blood markers for prognosis and efficacy: a retrospective cohort study.

Background: Alectinib is a second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs), which has attracted much attention in the treatment of ALK-positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed. This study assessed the efficacy of alectinib in patients with ALK-positive NSCLC and analyzed the prognostic factors. Methods: Patients with ALK-positive NSCLC who were confirmed by histopathology or cytology at the Affiliated Cancer Hospital of Nanjing Medical University between October 2018 and October 2021 were enrolled. All patients were treated with alectinib. The clinical characteristics and circulating tumor biomarkers before and after treatment were collected. Kaplan-Meier test was used to calculate the progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to explore the influencing factors on PFS. Incidence of adverse events was observed. Results: Twenty patients progressed after first-line treatment (n=59) with alectinib, and 21 patients progressed following second-line treatment (n=36) with alectinib. The median PFS of first-line treatment patients was not achieved, and the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23]. The most common adverse reactions were liver dysfunction (37.50%), anemia (37.50%), and constipation (20.83%). The incidence of grade III and above adverse reactions was 6.25%. Univariate analysis showed that neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR) =0.424, P=0.005] carcinoembryonic antigen (CEA; HR =0.482, P=0.029), lactate dehydrogenase (LDH; HR =0.327, P<0.001), carbohydrate antigen (CA)199 (HR =0.313, P=0.002), and circulating cell free DNA (cfDNA; HR =0.229, P=0.008) concentration levels were associated with PFS, and multivariate analysis showed that NLR (HR =3.058, P=0.034) was independent prognostic factor. After three months of treatment, CEA, CA199, NLR, and LDH, could further predict the prognosis of alectinib treatment. Conclusions: The efficacy and safety of alectinib as a first-line or second-line treatment for ALK-positive NSCLC in keeping with published prospective studies. CEA, CA199, NLR, and LDH within the normal range after three months of treatment were associated with good prognosis. Detection of serum tumor markers can indicate therapeutic success in patients treated with alectinib.

Effect of Loading Frequency Ratio on Multiaxial Asynchronous Fatigue Failure of 30CrMnSiA Steel.

Multiaxial asynchronous fatigue experiments were carried out on 30CrMnSiA steel to investigate the influence of frequency ratio on fatigue crack initiation and propagation. Test results show that the surface cracks initiate on the maximum shear stress amplitude planes with larger normal stress, propagate approximately tens of microns, and then propagate along the maximum normal stress planes. The frequency ratio has an obvious effect on the fatigue life. The variation of normal and shear stress amplitudes on the maximum normal stress plane induces the crack retardation, and results in that the crack growth length is longer for the constant amplitude loading than that for the asynchronous loading under the same fatigue life ratio. A few fatigue life prediction models were employed and compared. Results show that the fatigue life predicted by the model of Bannantine-Socie cycle counting method, section critical plane criterion and Palmgren-Miner's cumulative damage rule were more applicable.

[Migration of phenolic active ingredients in Danshen Dizhuye during ultrafiltration of hollow fiber membrane].

Study the suitability of organic film for salvianolic acid in the ultrafiltration process of Danshen Dizhuye. UPLC was used to analyze the migration of nine phenolic active ingredients in Danshen Dizhuye during ultrafiltration of PES hollow fiber membrane and PS hollow fiber membrane. The structural composition of multi-components was analyzed by three different batches of Danshen Dizhuye before and after ultrafiltration of the two membranes. The results showed that 9 phenolic active ingredients in Danshen Dizhuye did not change significantly after ultrafiltration through PES membrane. However, after ultrafiltration through PS membrane, the content of sodium danshensu, protocatechualdehyde, caffeic acid, 3-hydroxy-4-methoxycinnamic acid and rosmarinic acid in Danshen Dizhuye did not change significantly, while salvianolic acid D, salvianolic acid B and lithospermic acid decreased by about 20%, and the content of salvianolic acid A decreased significantly. The final content in equilibrium was only about 20% of the original solution. Therefore, an in-depth study on the migration particularity of salvianolic acid A in ultrafiltration membrane was the focuse. The results showed that the loss of salvianolic acid A was caused by both membranes during ultrafiltration, and salvianolic acid A was lost more in PS membrane. When the membrane was washed and regenerated, it was found that salvianolic acid A was detected in the ethanol washing solution, but not in the washing liquid, indicating that the loss of salvianolic acid A during the ultrafiltration was mainly adsorptive action. The results suggested that the migration of phenolic active ingredients in Danshen Dizhuye during the membrane ultrafiltration process did not completely follow the molecular weight passing rule of the membrane pore size. At the same time, it may be affected by factors, such as the structure of the membrane material, and the interaction between the membrane structure and the structure of components, and exhibit different migration behaviors during the ultrafiltration of the membrane.

[Mining and discovery for active components of "Coptidis Rhizome-Magnoliae Officinalis Cortex" based on network pharmacology].

To mine and discover the active components of " Coptidis Rhizome-Magnoliae Officinalis Cortex( C&M) " based on the network pharmacology,integrate and analyze the potential targets and mechanisms. The TCMSP database was used to screen active ingredients. TTD and Drug Bank databases were used to predict the potential targets by referring to relevant literature,and the pathway annotation technology was used to enrich and analyze the active ingredients and potential targets of " C&M". A total of 29 potential target active ingredients were screened from " C&M",including 12 alkaloids components such as( R)-canadine,berberine,coptisine,and palmatine; 3 lignans consisting of magnolol,honokiol and obovatol; 6 volatile oils consisting of α-eudesmol,ß-eudesmol,eucalyptol and so on,and flavonoids including quercetin and neohesperidin. Corresponding 199 predicted targets were screened out,mainly including PTGS2,PTGS1,NCOA2,Hsp90 AB1,and so on. 72 signaling pathways were involved,8 of which were related to cancer,such as prostate cancer,bladder cancer,and pancreatic cancer; 9 of which were related to endocrine,including oxytocin signaling pathway,insulin signaling pathway,thyroid hormone signaling pathway and so on,as well as inflammation-related pathway. This study has preliminarily mined and discovered the main active components and potential targets of " C&M",providing material source for the study on the preparation of structural components of traditional Chinese medicine.

The anti-inflammatory activity of several flavonoids isolated from Murraya paniculata on murine macrophage cell line and gastric epithelial cell (GES-1).

UNLABELLED: Context Murraya paniculata (L.) Jack (Rutaceae), Qianlixiang in Chinese, is distributed in China. As an important traditional Chinese medicine (TCM), it demonstrates many bioactivities, such as febrifuge, astringent, anti-dysenteric, and tonic. OBJECTIVE: The objective of this study is to evaluate the anti-inflammatory effect of three flavonoids isolated from M. paniculata in lipopolysaccharide (LPS)-activated murine macrophage cell line and ethanol-induced gastric damage on gastric epithelial cell (GES-1). Materials and methods Three identified flavonoids were isolated from stems and leaves of M. paniculata using ultra performance liquid chromatography (UPLC). Cell viability was measured with MTT, mouse peritoneal macrophages and GES-1 cells were incubated with 0, 0.01, 0.1, 1, 10, and 100 µM P1, P3 and P8 for 24, 48, and 72 h. The inhibitory effect of pretreatment with various concentrations of 5,7,3',4',5'-pentamethoxyflavone (P1), 5,7,3',4'-tetramethoxyflavone (P3), or 5-desmethylnobiletin 5-hydroxy-6,7,8,3',4'-pentameth-oxyflavone (P8) ranging from 0.03 to 30 µM on nitric oxide (NO) secretion was quantified by the Griess assay for 24 and 48 h, while interleukin-6 (IL-6) was measured by ELISA for 24 and 48 h. Results The effects of P1, P3, and P8 on mouse peritoneal macrophages and GES-1 cells were not attributable to cytotoxic effects at the doses of 0-10 µM. The IC50 value of P1 is 53.40 µM, P3 is 120.98 µM, and P8 is 10.73 µM. The concentration of the three flavonoids had the best effects of anti-inflammation upon NO inhibition at the dose of 3 µM. P3 had the highest inhibition on IL-6 production. The GES-1 cells pretreated with three flavonoids showed a significant increase in the level of NO (P1: 7.94 ± 0.0635 µM, P3: 8.81 ± 0.0159 µM, and P8: 8.51 ± 0.0522 µM) at 24 h and a more significant increase at 48 h (P1: 9.34 ± 0.0975 µM, P3: 11.9 ± 0.0672 µM, and P8: 9.34 ± 0.0454 µM). Discussion and conclusion The current results suggested that the anti-inflammatory activity of three flavonoids was mainly manifested in the reduction of production of NO and IL-6 production. Analysis of the structure-activity relationship indicated that the double bond at C2-C3 and the position of the B ring at C2/C3 seemed to be indispensable for the anti-inflammatory activity.