Two important factors affecting the prognosis of patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma

ObjectiveTo investigate the effects of hand–foot syndrome (HFS) and fatigue on disease progression and survival in patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma.MethodsA retrospective analysis of patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from 1 October 2018 to 31 October 2021 was performed, and clinical and pathological data and follow-up results were obtained. Patients were divided into groups according to the severity of HFS and fatigue. Survival analysis among the groups was performed using the Kaplan–Meier method, continuous variables were analyzed using the t-test, and factors associated with survival were evaluated using multivariate Cox regression analysis.ResultsThe study included 150 men and 23 women with a mean age of 60.77 years (range: 40–85 years). The median overall survival (OS), progression-free survival (PFS), and time to tumor progression (TTP) increased with increasing severity of HFS. Conversely, the median OS, PFS, and TTP decreased with increasing severity of fatigueConclusionHFS and fatigue were independent risk factors affecting TTP, PFS, and OS among patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma.     

Polydiacetylene-based colorimetric and fluorometric sensors for lead ion recognition

Development of novel sensors for the detection of lead ions (Pb²⁺) has attracted increasing interest due to their inherent toxic effects on human health and the environment. In this study, we describe two new polydiacetylene (PDA)-based liposome sensors for the colorimetric and fluorometric recognition of Pb²⁺ in aqueous solution. In the sensor system, a thymine-1-acetic acid (TAA) or orotic acid (OA) group was reasonably introduced into the diacetylene monomer to work as a strong binding site for Pb²⁺. The TAA- or OA-functionalized monomer and 10,12-pentacosadiynoic acid (PCDA) were incorporated into PDA liposomes in aqueous solution. After UV light-induced polymerization, deep blue colored liposome solutions were obtained. Upon the addition of a series of transition metal cations into the liposome solutions, only Pb²⁺ could induce a color change from blue to red observable by the naked eye and a large fluorescence enhancement. The results clearly showed that the PDA–EDEA–TAA and PDA–EDEA–OA liposomes could act as highly selective and sensitive probes to detect Pb²⁺ in aqueous solution. The detection limits of PDA–EDEA–TAA and PDA–EDEA–OA systems are 38 nM and 25 nM, respectively. The excellent selectivity of PDA liposomes could be attributed to the stronger complexation behavior of Pb²⁺ with TAA (or OA) and the carboxylic acid at the lipid–solution interface which could perturb the PDA conjugated backbone. In addition, the proposed sensors were successfully applied to detect trace amounts of Pb²⁺ in real water samples with excellent recovery, indicating that the developed method had a good accuracy and precision for the analysis of trace Pb²⁺ in practical samples.

In this study two colorimetric and fluorometric sensors were prepared for lead ions based on conjugated polydiacetylenes.     

Improved nitrogen reduction activity of NbSe2 tuned by edge chirality

Efficient catalysts for the electroreduction of N₂ to NH₃ are of paramount importance for sustainable ammonia production. Recently, it was reported that NbSe₂ nanosheets exhibit an excellent catalytic activity for nitrogen reduction under ambient conditions. However, existing theoretical calculations suggested an overpotential over 3.0 V, which is too high to interpret the experimental observations. To reveal the underlying mechanism of the high catalytic activity, in this work, we assessed NbSe₂ edges with different chirality and Se vacancies by using first principles calculations. Our results show that N₂ can be efficiently reduced to NH₃ on a pristine zigzag edge via the enzymatic pathway with an overpotential of 0.45 V. Electronic structure analysis demonstrates that the N₂ molecule is activated by the back-donation mechanism. The efficient tuning of the local chemical environments by edge chirality provides a promising approach for catalyst design.

The zigzag edge of the NbSe₂ monolayer exhibits an overpotential as low as 0.45 V along the enzymatic pathway.     

Preparation,characterization and in vitro study of bellidifolin nano-micelles

Bellidifolin (BEL), a xanthone compound, has significant therapeutic effectiveness in cardiac diseases such as arrhythmias. However, BEL is limited in clinical applications by its hydrophobicity. In this work, we used BEL as the active pharmaceutical ingredient (API), and polyethylene glycol 15-hydroxy stearate (Kolliphor HS15) as the carrier to prepare BEL nano-micelles by a solvent-volatilization method. According to an analysis by differential scanning calorimetry (DSC), BEL was successfully encapsulated in HS15 as BEL nano-micelles with a 90% encapsulation rate, and particle size was 12.60 ± 0.074 nm in the shape of a sphere and electric potential was −4.76 ± 4.47 mV with good stability and sustained release characteristics. In addition, compared with free drugs, these nano-micelles can increase cellular uptake capacity, inhibit the proliferation of human cardiac fibroblasts, and down-regulate the expression of Smad-2, α-SMA, Collagen I, and Collagen III proteins in myocardial cells to improve myocardial fibrosis. In conclusion, the BEL nano-micelles can provide a new way for the theoretical basis for the clinical application of anti-cardiac fibrosis.

Bellidifolin (BEL), a xanthone compound, has significant therapeutic effectiveness in cardiac diseases such as arrhythmias.     

Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

BackgroundThe pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking.MethodsA chronic migraine model was established by repeated inflammatory soup stimulation. Mechanical, periorbital, and thermal pain thresholds were assessed by the application of von Frey filaments and radiant heat. The mRNA and protein expression levels of the dopamine D2 receptor were analyzed by qRT‒PCR and western blotting. Colocalization of the dopamine D2 receptor and the GLUA1-containing AMPAR was observed by immunofluorescence. A dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride), a PI3K inhibitor (LY294002), a PI3K pathway agonist (740YP), and a GLUA1-containing AMPAR antagonist (NASPM) were administered to confirm the effects of the dopamine D2 receptor, the PI3K pathway and GULA1 on central sensitization and the GLUA1-containing AMPAR trafficking. Transmission electron microscopy and Golgi-Cox staining were applied to assess the impact of the dopamine D2 receptor and PI3K pathway on synaptic morphology. Fluo-4-AM was used to clarify the role of the dopamine D2 receptor and PI3K signaling on neuronal calcium influx. The Src family kinase (SFK) inhibitor PP2 was used to explore the effect of Src kinase on GLUA1-containing AMPAR trafficking and the PI3K signaling pathway.ResultsInflammatory soup stimulation significantly reduced pain thresholds in rats, accompanied by an increase in PI3K-P110β subunit expression, loss of dopamine receptor D2 expression, and enhanced GLUA1-containing AMPA receptor trafficking in the trigeminal nucleus caudalis (TNC). The dopamine D2 receptor colocalized with the GLUA1-containing AMPA receptor in the TNC; quinpirole, LY294002, and NASPM alleviated pain hypersensitivity and reduced GLUA1-containing AMPA receptor trafficking in chronic migraine rats. Sulpiride aggravated pain hypersensitivity and enhanced GLUA1 trafficking in CM rats. Importantly, the anti-injury and central sensitization-mitigating effects of quinpirole were reversed by 740YP. Both quinpirole and LY294002 inhibited calcium influx to neurons and modulated the synaptic morphology in the TNC. Additional results suggested that DRD2 may regulate PI3K signaling through Src family kinases.ConclusionModulation of GLUA1-containing AMPA receptor trafficking and central sensitization by the dopamine D2 receptor via the PI3K signaling pathway may contribute to the pathogenesis of chronic migraine in rats, and the dopamine D2 receptor could be a valuable candidate for chronic migraine treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01469-x.     

生物陶瓷材料(七)

2.3.2 与有机物或生物活性物质复合 　　骨骼中除了无机成分外,还含有少量的有机成分,其中23%是胶原,还含有一些生物活性物质.将这些有机物或生物活性物质复合到HAC中在一定程度上无疑会提高其性能.……     

生物陶瓷材料(八)

2.4.2在骨折固定术中辅助加固的应用研究HAC在骨折治疗中的应用目前多见于对松质骨骨折内固定的加强。Constantz等将HAC经皮注射到骨折部位,发现在骨折愈合过程中HAC能提供     

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer

Accurate methods for identifying pelvic lymph node metastasis(LNM)of prostate cancer(PCa)prior to surgery are still lacking.We aimed to investigate the predicti...     

保罗青光眼植入物治疗青光眼的初步观察

目的：初步评估保罗青光眼植入物在青光眼治疗中的有效性和安全性。

方法：回顾性分析2022-03/2023-01接受保罗青光眼植入物治疗的青光眼患者10例10眼的临床资料。至少随访12 mo,观察手术前后视力、眼压和抗青光眼用药数量等指标的变化。

结果：纳入患者末次随访时视力较术前无明显变化; 术前眼压19-60(中位数28)mmHg,末次随访时眼压为10-18(中位数14)mmHg。术前所有患者均需使用2-4种抗青光眼药物,末次随访时仅1例患者需使用。4例患者末次随访时角膜内皮细胞密度较术前明显下降,未发生角膜相关并发症。截至末次随访,10例患者均获得手术成功。

结论：保罗青光眼植入物具有显著的降眼压疗效,角膜内皮细胞损害可能是其存在的隐患。