Real-World Prescription Patterns For Patients With Young-Onset Parkinson's Disease in China: A Trend Analysis From 2014 to 2019.

Introduction Pharmacotherapy is one of the main treatments for patients with young-onset Parkinson's disease (YOPD). Although numerous studies on the treatment of YOPD have been published, the real-world prescription patterns of these populations remain unclear in China. Methods A national comprehensive evaluation was performed to reveal the pharmacological treatment patterns in Chinese patients with Parkinson's disease from 1 January 2014 to 31 December 2019, with patients aged 21-50 years classified as having YOPD for the subgroup analysis. Information on patients and drugs was extracted to analyse the demographic characteristics, prescription patterns, and levodopa equivalent daily dose (LED) during disease progression. Results A total of 1,134 patients with YOPD were included, and the majority were aged 41-50 years. Prescription of L-DOPA/benserazide and pramipexole accounted for more than 30 and 20%, respectively, in each year from 2014 to 2019. There was no difference in prescription patterns in terms of age, sex and geographical areas. Half of the patients with YOPD were on monotherapy, but the proportion decreased from 2016. Correspondingly, the proportion of patients receiving polytherapy increased, especially those who were prescribed more than two anti-Parkinson's disease drugs. During the disease course, LED showed high variability, which increased over time. Conclusion L-DOPA/benserazide and pramipexole were the most frequently prescribed anti-PD drugs for patients with YOPD in China. There was a slight trend in the transition from monotherapy to polytherapy. LED increased with disease duration. Thus, we provided an overview of the prescription patterns for patients with YOPD in China.

Review of HPLC-MS methods for the analysis of nicotine and its active metabolite cotinine in various biological matrices.

In recent years, tobacco smoking is a risk factor for a series of diseases, including cardiovascular diseases, cerebrovascular diseases, and cancers. Nicotine, the primary component of tobacco smoke, is mainly transformed to its active metabolite cotinine, which is often used as a biomarker for tobacco exposure for its higher blood concentration and longer residence time than nicotine. Various analytical methods have been developed for the determination of nicotine and cotinine in biological matrices. This article reviewed the HPLC-MS based methods for nicotine and/or cotinine analysis in various biological matrices. The sample preparation, mass and chromatographic conditions, and method validation results of these methods have been summarized and analyzed. The sample was mainly pretreated by protein precipitation and/or extraction. Separation was achieved using methanol and/or acetonitrile:water (with or without ammonium acetate) on C18 columns and acetonitrile:water (with formic acid, ammonium acetate/formate) on HILIC columns. Nicotine-d3, nicotine-d4, and cotinine-d3 were commonly used internal standards (ISs). Other non-deuterated ISs such as ritonavir, N-ethylnorcotinine, and milrinone were also used. For both nicotine and cotinine, the calibration range was 0.005-35,000 ng/mL, the matrix effect was 75.96-126.8%, and the recovery was 53-124.5%. The two analytes were stable at room temperature for 1-10 days, at -80°C for up to 6 months, and after three to six freeze-thaw cycles. Comedications did not affect nicotine and cotinine analyses.

Construction and sustained release of konjac glucomannan/naringin composite gel spheres.

Objective: To improve the bioavailability of active substances and reduce the toxic and side effects on the human body, natural biological macromolecules are used to load active substances and control their release speed in different environments of the human body. In this study, mesoporous silica (MSN) was combined with konjac glucomannan (KGM) and sodium alginate (AC) to prepare pH-sensitive konjac glucomannan/sodium alginate-mesoporous silica loaded naringin gel spheres (KS/MSN). On this basis, the structure, morphology, and release properties of the composite gel spheres were characterized. The results showed that the cumulative release rates of both simulated gastric fluid (SGF) and Simulated colonic fluid (SCF) were lower than that of simulated small intestinal fluid (SIF), which indicated that the prepared composite gel spheres were pH-sensitive to SIF and obtained the best release rate of about 70% under SIF environment. Methods: The pH-sensitive konjac glucomannan/sodium alginate composite gel spheres (KGM/SA) were prepared by combining inorganic nano-materials mesoporous silica (MSN) with natural macromolecular polysaccharides konjac glucomannan (KGM) and sodium alginate (SA) and characterized. Results: The results showed that there was a process of ionic crosslinking and entanglement between konjac glucomannan (KGM) and sodium alginate (SA). Naringin (NG) and mesoporous silica (MSN) were successfully compounded and had good compatibility. The gel microstructure diagram showed that the addition of MSN improved the gel properties of KGM, and KGM and SA gel spheres (KGM/SA) had good compatibility with mesoporous silica/naringenin nanoparticles (NG/MSN). The study of the simulated digestive environment of the gastrointestinal release medium showed that Konjac glucomannan/sodium alginate-mesoporous silica loaded naringin gel spheres (KS/NM) composite gel spheres had the best slow-release effect and the highest final-release completion degree in SIF. The release of NG from KS/NM composite gel spheres showed a slow upward trend. The results showed that KS/NM composite gel spheres were pH-sensitive. Conclusion: The KS/NM composite gel spheres showed obvious pH sensitivity to the release of NG, and the gel spheres had a good sustained release effect on NG.

Development and progress of clinical trials of Coronavirus Disease 2019 antiviral drugs.

INTRODUCTION: We have summarized and analyzed the clinical trial registration status and the latest research progress of eight major antiviral drugs during the epidemic of Coronavirus Disease 2019 (COVID-19), which can provide reference methods for clinical formulation of the best antiviral treatment. AREAS COVERED: We used the generic names of 8 antiviral drugs as keywords to search and analyze the COVID-19-related clinical trials registered in Chinese Clinical Trial Registry and ClinicalTrials.gov. Then, we used the keywords to obtain and summarize their clinical research results related to COVID-19 in CNKI, WANFANG, CQVIP, and PubMed database. EXPERT OPINION: The registration system of clinical trials and the level of clinical trial design need to be further improved. At present, no specific drug has been found for the treatment of COVID-19, the efficacy of antiviral drugs mostly comes from small sample studies or retrospective studies, and the level of clinical evidence is low. Besides, multi-drug combination therapy may become a more effective treatment choice, but the drug interactions and adverse drug reactions also need to be closely monitored. In summary, the safety and efficacy of various antiviral drugs need to be confirmed by large samples and high-quality RCT studies.

Crosstalk Between Acid Sphingomyelinase and Inflammasome Signaling and Their Emerging Roles in Tissue Injury and Fibrosis.

Inflammasomes are a group of protein complexes that are assembled by pattern recognition receptors following the recognition of invading pathogens or host-derived danger signals. Inflammasomes such as NLRP3 mediate the activation of caspase-1 and the production of the proinflammatory cytokines IL-18 and IL-1ß. Regulation of inflammasome signaling is critical for host defense against infections and maintenance of cellular homeostasis upon exposure to multiple harmful stimuli. Recent studies have highlighted an important role of acid sphingomyelinase (ASM) in regulating inflammasome activation. ASM hydrolyzes sphingomyelin to ceramide, which further fuses to large ceramide-enriched platforms functioning in stabilizing and amplifying molecules and receptors. Here, we will discuss the current understanding of the ASM-ceramide system in inflammasome activation, and how it contributes to multiple diseases. Insights into such mechanisms would pave the way for further exploration of novel diagnostic, preventative, and therapeutic targets against tissue injury and fibrosis.

Current development and patents on high-brightness white LED for illumination.

In this paper, we reviewed the current development and patents for the application of high-brightness and high-efficiency white light-emitting diode (LED). The high-efficiency GaN nanostructures, such as disk, pyramid, and rod were grown on LiAlO(2) substrate by plasma-assisted molecular-beam epitaxy, and a model was developed to demonstrate the growth of the GaN nanostructures. Based on the results, the GaN disk p-n junction was designed for the application of high brightness and high efficiency white LED.