Intrathecal chemotherapy combined with systemic therapy in patients with refractory leptomeningeal metastasis of non-small cell lung cancer: a retrospective study.

BACKGROUND: Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. There is currently no standard treatment for LM, and the efficacy of traditional intravenous drug treatment is low, making refractory LM a difficult problem. In this study, we evaluated the efficacy and safety of intrathecal chemotherapy (IC)-based regimens in patients with refractory LM. METHODS: We retrospectively enrolled NSCLC patients with confirmed LM who received IC and systemic therapy at the Second Affiliated Hospital of Nanchang University from December 2017 to July 2022. We analysed overall survival (OS), intracranial progression-free survival (iPFS), clinical response, and safety in these patients. RESULTS: A total of 41 patients were enrolled. The median number of IC treatments was seven (range: 2-22). Seven patients received intrathecal methotrexate, and 34 patients received intrathecal pemetrexed. Clinical manifestations related to LM improved after IC and systemic therapy in 28 (68.3%) patients. The median iPFS in the whole cohort was 8 months (95% confidence interval [CI]: 6.4-9.7 months), and the median OS was 10.1 months (95% CI: 6.8-13.4 months). Multivariate analysis of the 41 patients with LM using a Cox proportional risk model showed that bevacizumab was an independent prognostic factor in patients treated with combination therapy (p = 0.002; hazard ratio [HR] 0.240; 95% CI: 0.097-0.595). Poor ECOG performance status remained a significant predictor of poor prognosis for survival (p = 0.048; HR 2.560; 95% CI: 1.010-6.484). Myelosuppression was the major adverse event over all IC dose levels. There were 18 cases of myelosuppression, 15 cases of leukopenia, and nine cases of thrombocytopenia. Eleven patients had myelosuppression above grade 3, including four with thrombocytopenia and seven with leukopenia. CONCLUSIONS: Combination therapy based on IC had good curative effects, was safe to use, and was associated with prolonged survival in NSCLC patients with LM. The use of bevacizumab is a good prognostic factor for NSCLC LM patients with combination therapy.

Aqueous extracts of Lindera aggregate (Sims) Kosterm leaves regulate serum/hepatic lipid and liver function in normal and hypercholesterolemic mice.

The leaves of Lindera aggregate (Sims) Kosterm. are traditionally used as healthy tea for the prevention and treatment of hyperlipidemia in Chinese. The aim of this study was to evaluate the antihyperlipidemic effects and potential mechanisms of the aqueous extracts from L. aggregate leaves (AqLA-L) on normal and hypercholesterolemic (HCL) mice. HCL mice were induced by high fat diet (HFD) and orally administrated with or without AqLA-L for ten days. The results showed that AqLA-L (0.3, 0.6, 1.2 g/kg) significantly reduced serum TG, ALT, but elevated fecal TG in normal mice. AqLA-L (0.3, 0.6, 1.2 g/kg) also remarkably lowered serum TC, TG, LDL, N-HDL, ALT, GLU, APOB, hepatic GLU and increased serum HDL, APOA-I, fecal TG levels in HCL mice. These results revealed that AqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice. The potential mechanisms for cholesterol-lowering effects of AqLA-L might be up-regulation of cholesterol 7-alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1), as well as down-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). The data indicated that AqLA-L has potential therapeutic value in treatment of hyperlipidemia with great application security.

Association Between the Prognostic Nutritional Index and Cognitive Function Among Older Adults in the United States: A Population-Based Study.

BACKGROUND: Nutritional status has been recognized as an important factor influencing cognitive function-related diseases, but few comprehensive nutrition indicators are available to assess the risk of cognitive decline. OBJECTIVE: This study aimed to investigate the relationship between the prognostic nutritional index (PNI) and cognitive function in an elderly population, and the differences in nutrient intake between different levels of nutritional risk. METHODS: Based on cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we included 2,564 older participants. The lower quartile of each of the four cognitive tests was considered to have cognitive function impairment (CFI). Binary and multivariate logistic regression models were used to estimate the relationship between the PNI and the odds ratio of CFI. RESULTS: After adjustment for confounding variables, we found that the odds of CFI were significantly lower for participants with normal PNI levels than for those with low PNI levels. In a comparison of global cognitive impairment scores, participants with a normal PNI had lower ratios of poor cognitive performance than those with a low PNI. By comparing the nutrient intake at different PNI levels, we found a reduction in the intake of protein, dietary fiber, total saturated fatty acids, and multiple micronutrients in the low PNI group. CONCLUSION: Our study shows that the PNI can be a good predictor of the odds of CFI in the elderly population and that it is a convenient indicator of reduced intake of nutrients which may be important to brain health.

Effects of template molecules on the structures and luminescence intensities of a series of porous Tb-MOFs based on the 2-nitroterephthalate ligand.

Four novel porous Tb(iii) metal-organic frameworks (Tb-MOFs) have been designed and prepared hydrothermally from 2-nitroterephthalate (2-H2ntp), namely {[Tb(2-ntp)1.5(H2O)]·H2O} n (1), {[Tb(2-ntp)2(H2O)]·4,4'-Hbipy} n (2), {[Tb(2-ntp)2(H2O)]·2,4-Hbipy} n (3), and {[Tb(2-ntp)2(H2O)]·(1,4-H2bbi)0.5} n (4) (4,4'-bipy = 4,4'-bipyridine; 2,4-bipy = 2,4-bipyridine; 1,4-bbi = 1,4-bisbenzimidazole). X-ray diffraction structural analyses show these Tb-MOFs are porous and are based on Tb3+ ions and 2-nitroterephthalate, in which water molecules (1) or protonated N-donor ligands (2-4) exist as templates. The fluorescence properties of complexes 1-4 could be associated with the characteristic peaks of Tb(iii) ions, and the existence of different guest molecules affects the intensities of peaks, which means that these could be potential fluorescence materials, with intensities adjusted using guests.

Prokaryote expression of HPeV-1 VP1 protein, production of VP1 polyclonal antibody and the development of an ELISA.

The VP1 protein of human parechovirus (HPeV) plays a critical role in receptor binding based on its functional arginine-glycine-aspartic acid (RGD) motif region. Currently, only the neutralisation assay is used for seroepidemiological surveys of HPeVs. In the present study, the VP1 gene of HPeV-1 was cloned into the vector pET28a(+) to express the His-tagged VP1 protein in the bacterium Escherichia coli Rosetta. The recombinant protein was purified from inclusion bodies by Ni(+)-NTA affinity chromatography under denaturing conditions, followed by a refolding process in gradient urea. The identity and antigenicity of the His-tagged protein was confirmed by Western blotting using an anti-His monoclonal antibody and human HPeV-1-positive serum respectively. Polyclonal antibodies against the His-tagged VP1 protein were raised in rabbits by standard procedures, and the reactivity and specificity were tested by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. An indirect ELISA was developed based on the fusion protein VP1, and evaluated in order to facilitate the detection of antibodies in persons who had been infected naturally with HPeVs. A serological survey was performed using the assay amongst children in the Shanghai region of China; the seropositivity rate was found to be about 73%.