Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To establish and validate a method for simultaneous determination of 9 sedative-hypnotics in human plasma,and to explore the preliminary clinical application.Methods Plasma samples were precipitated with acetonitrile and determined by high performance liquid chromatography tandem mass spectrometry.The column was Agilent Poroshell 120 EC-C18(2.1 mm × 50.0 mm,2.7μm)and eluted with acetonitrile water containing 0.1％formic acid in an equal degree program at a flow rate of 0.3 mL·min-1.The column temperature was 20 ℃ and injection volume was 5 μL.The deprotonated ions of analytes were ionized by positive ion,electron spray ionization and multiple reaction monitoring mode.The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,stability and dilution effect of the method were investigated.Results Excellent linear relationship with correlation coefficient of r2 ≥ 0.997 7 was obtained.The linear of esazolam,alprazolam,oxazepam,clonazepam,lorazepam,triazolam,midazolam,diazepam and zolpidem were 18-1 800,4.5-450,25-2 500,3.5-350,25-2 500,1.5-150,5.5-550,35-3 500,4-400 ng·mL-1,respectively.The lower limit of quantification were 18,4.5,25,3.5,25,1.5,5.5,35,4 ng·mL-1.The method was accurate and precise with acceptable intra-day and inter-day precisions(relative standard deviations were less than 20％for a lower limit of quantification and less than 15％for other quality control samples)and an accuracy of 86.21％-112.38％.The extraction recovery rate were 93.07％-110.50％.The matrix factors normalized by internal standard were 86.61％-108.41％,relative standard deviations were less than 15％.Plasma samples remained stable under various storage conditions.The precision and accuracy of plasma samples were acceptable after dilution.Conclusion The method is simple,rapid,sensitive and specific,and it can be used for simultaneous detection of the 9 sedative-hypnotics in human plasma.

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca²⁺ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca²⁺ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

Good medicine tastes bitter, but it is often difficult to swallow because the drug is bitter and astringent, so that the compliance of patients with medication is poor. However, the use of taste masking technology can better improve this situation. Appropriate and effective taste masking technology can improve the drug compliance of patients, especially children, it can also improve the curative effect and the clinical value of drugs. Herein, we summarize the latest research progress of taste masking technology, and summarize the traditional taste masking technology from the aspects of action mechanisms and application scopes. Finally, the novel and efficient taste masking technologies were presented.

Aim To investigate the effect of terpinen-4-ol (T40) on inflammatory injury of vascular smooth muscle cells (VSMCs) induced by high glucose based on the improvement of autophagic flow disorder and involved molecular signals. Methods The scratch test was used to analyze the migration ability of VSMCs, the levels of IL-1β and IL-6 in cell culture supernatant were measured by ELISA, the expression levels of inflammation-related proteins NF-κb p65, p-NF-κb p65, IL-1β, IL-18 and autophagy-related proteins p62, LC3-HYLC3-I, Beclinl, p-Beclinl were de-tected by Western blot. Results T40 inhibited migration of VSMCs induced by high glucose, reduced the secretion and release of pro-inflammatory factors IL-1β and IL-6, inhibited the expression of p-NF-κb p65/ NF-κb p65, IL-1β, IL-18, downregulated the expression of p62, LC3-TJ/LC3- I and p-Beclinl at same time. After interfering the autophagic flux of VSMCs with autophagy inhibitor chloroquine (CQ) , T40 pre-treatment significantly inhibited the protein expression levels of the above inflammatory factors and autophagy-related signals which mediated by CQ. Conclusion T40 inhibits the inflammatory injury of VSMCs induced by high glucose through improving the autophagic flow disorder.

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1β, MIP-1α, MCP-1, CCL5, IP-10, and IFN-β, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-β by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.
Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Plant Extracts/metabolism* ; Lipopolysaccharides/pharmacology* ; Macrophages ; Cytokines/metabolism* ; RNA, Messenger/metabolism*

Aim To investigate the eorrelation between angiotensin II (Ang II ) level and clinical indicators in patients with rheumatoid arthritis ( HA) , and to determine the therapeutic effect of angiotensin receptor blockers ( ARBs).Methods Plasma samples and personal information were collected from HA patients admitted to our hospital from 2019 to 2021.The level of Ang II in plasma was determined by ELISA to elucidate the correlation between plasma Ang II level and the severity of HA.The pathological changes of synovi-al tissues and T eells subtype in different groups of HA patients were determined by pathological examination and flow cytometry.A rat model of collagen-induced arthritis (CIA) was established and the pathological examination was used to confirm that valsartan could alleviate the disease course in the CIA animal model.Results Compared with control group, the plasma level of Ang II in HA patients significantly increased.After therapy with oral ARBs plasma Ang H levels and anti - cyclic citrullinated peptide antibody ( CCP) titre were significantly lower than those untreated HA patients.The level of Ang II in plasma was positively correlated with CCP and the number of monocytes, but negatively with number of RBC and hemoglobin content.Staining of synovial tissue with HE and Masson found that patients with HA had significant synovial proliferation, pannus formation , and numerous inflammatory cell infiltrates compared with control patients.Immunohistochemical results showed significant infiltration of CD4 4 T cells in synovial tissues of HA patients.Western blot and immunofluorescence analysis showed that the expression of angiotensin type 1 receptor ( ATI R ) was significantly up-regulated in CD4 + T cells and synovial tissues of HA patients.The results of animal experiments showed that valsartan harl therapeutic effect on CIA rats and could delay the disease process of CIA.Conclusions Plasma Ang II level is positively correlated with CCP level and HA severity.ARBs can down-regualte CCP level and delay disease progression in HA patients.Animal experiments showed that valsartan blocks the combination of Ang H and ATI R and has therapeutic effect on a CIA rat model.This study provides the theoretical and experimental basis for ARBs to become the preferred antihypertensive drugs for HA patients with hypertension.

Aim To investigate the effect and mechanism of salidroside (SAL) on homocysteine (Hcy)-induced endothelial-mesenchymal transition (EndMT) based on the KLF4/eNOS signaling pathway. Methods (1) Salidroside inhibited Hcy-induced EndMT. HUVECs were pretreated with different concentrations of SAL for 2 h, then followed by Hcy (1 mmol · L-l) co-incubation for 48 hours to induce EndMT. The expression levels of VE-cadherin, α-SMA, KLF4 and eNOS were detected by Western blot, scratch repair experiment was used to determin cell migration ability, the level of NO in cells was determined by nitrate reductase method, and the expression and location of KLF4 were observed by immunofluorescence technology. (2) The signal mechanism of SAL inhibiting End-MT through KLF4/eNOS signal was studied. siRNA mediated knockdown of KLF4 in HUVECs, and the protein expression levels of VE-cadherin, α-SMA, KLF4 and eNOS in each group were determined by Western blot. Results Western blotting demonstrated that SAL significantly reversed the Hcy-induced increase in α-SMA and KLF4 expression and decrease in VE-cadherin and eNOS expression. The immunofluorescence analysis suggested that SAL inhibited the translocation of KLF4 from cytoplasm to nucleus. (2) Silencing KLF4 down-regulated the expression of α-SMA and KLF4, and up-regulated the expression of VE-cadherin and eNOS. Compared with the group of SAL + siKLF4, there was no significant difference in the effect of SAL group and siKLF4 group on phenotypic markers. Conclusions Salidroside inhibits EndMT induced by Hcy, which may be related to the regulation of KLF4/eNOS signaling pathway.

Objective: To explore the expression of the N-methyl-D-aspartate (NMDA) receptor in the rat model of orchialgia and its possible mechanisms. METHODS: According to Yoshioka's method, the male rats in the control group were injected with 0.2 ml saline, and those in the experimental group with 0.2 ml 2% acetic acid solution. Then we tested the behavioral responses of the rats and determined the expressions of the subunits NR1 and NR2B of the NMDA receptor in the dorsal root ganglion and spinal dorsal horn by Western blot, RT-qPCR and immunofluorescence staining. RESULTS: The withdrawal latency was decreased in the model rats, reaching the lowest value at 4 hours after modeling, significantly lower than in the controls (［4.15 ± 0.84］ vs ［12.32 ± 1.05］, P < 0.05). Compared with the controls, the model rats showed remarkably increased mRNA and protein expressions of NR2B in the dorsal root ganglion (P < 0.05) but not in the spinal dorsal horn at 4 hours. However, no statistically significant difference was found in the expression of NR1 either in the dorsal root ganglion or in the spinal dorsal horn between the two groups (P > 0.05). CONCLUSIONS The NMDA receptor plays an important role in pathogenesis of orchialgia in rats. In the early stage of pain, upregulating the expression of the subunit NR2B of the NMDA receptor can mediate peripheral hyperalgesia and consequently orchialgia.