Analysis of post-market adverse events of istradefylline: a real-world study base on FAERS database.

Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.

Investigating the Mechanism of Chufan Yishen Formula in Treating Depression through Network Pharmacology and Experimental Verification.

Objective: To investigate the antidepressant effect and potential mechanism of the Chufan Yishen Formula (CFYS) through network pharmacology, molecular docking, and experimental verification. Methods: The active ingredients and their target genes of CFYS were identified through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed genes in patients with depression from the GEO database and screened out the genes intersecting with the target genes of CFYS to construct the PPI network. The key pathways were selected through STRING and KEGG. Then, molecular docking and experimental verification were performed. Results: A total of 113 effective components and 195 target genes were obtained. After intersecting the target genes with the differentially expressed genes in patients with depression, we obtained 37 differential target genes, among which HMOX1, VEGFA, etc., were the key genes. After enriching the differential target genes by KEGG, we found that the "chemical carcinogenesis-reactive oxygen species" pathway was the key pathway for the CFYS antidepressant effect. Besides, VEGFA might be a key marker for depression. Experimental verification found that CFYS could significantly improve the behavioral indicators of rats with depression models, including improving the antioxidant enzyme activity and increasing VEGFA levels. The results are consistent with the network pharmacology analysis. Conclusions: CFYS treatment for depression is a multicomponent, multitarget, and multipathway complex process, which may mainly exert an antidepressant effect by improving the neuron antioxidant stress response and regulating VEGFA levels.

Practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals during COVID-19 pandemic in Wuxi, China.

Objective: To study the practice of pharmaceutical services in internet-based psychiatric hospitals, and to analyze the prescriptions to ensure the safety and efficacy of internet-based medication in Wuxi, China. Methods: All 1,259 internet-based prescriptions from our hospital in 2022 were collected, and data on patients' age, gender, diagnosis, medications used, medication types, dosage forms, rationality of medication use, and reasons for irrationality were analyzed through descriptive statistics. Results: In the electronic prescriptions of internet-based psychiatric hospitals, females accounted for the majority (64.50%), with a female-to-male ratio of 1.82:1. Middle-aged and young adults accounted for the majority of patients (57.50%). There were 47 diagnosed diseases involved, with 89 types of medications used and 1,938prescriptions issued. Among them, there were 78 types of western medicine with 1,876 prescriptions (96.80%), and 11 types of traditional Chinese medicine with 62 prescriptions (3.20%). The main medications used were anti-anxiety and antidepressant medications (44.94%) and psychiatric medications (42.21%). The dosage forms were all oral, with tablets (78.53%), capsules (17.54%), and solution preparations (2.17%) being the top three in frequency. According to the prescription review results, the initial pass rate of internet-based system review was 64.26%. After intervention by the internet-based system and manual review by pharmacist reviewers, the final pass rate of internet-based prescriptions reached 99.76%. Conclusion: The practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals could significantly improve medication rationality, which fills the research gap in this field. In addition, it promotes the transformation of pharmaceutical service models.

Case report: Endoscopic frontal sinus opening surgery for noninflammatory frontal sinus headache: A short case series.

Objective: The objectives of this study were to analyze rhinogenic headache, i.e., noninflammatory frontal sinus headache, a headache caused by bony obstruction of the frontal sinus drainage channels that receives relatively insufficient attention clinically, and to propose endoscopic frontal sinus opening surgery as a treatment based on the etiology. Study Design: Case series. Setting: From the data of patients with noninflammatory frontal sinus headache who underwent endoscopic frontal sinus surgery in Hospital of Chengdu University of Traditional Chinese Medicine during 2016-2021, data for three cases with detailed postoperative follow-up data were extracted for case series reports. Methods: This report provides detailed information on three patients with noninflammatory frontal sinusitis headache. Treatment options include surgery and rechecking, with the visual analogue scale (VAS) scores of preoperative and postoperative symptoms, CT, and endoscopic images. Three patients had common characteristics: the clinical manifestations were recurrent or persistent with pain and discomfort in the forehead area, but there was no nasal obstruction or runny nose; the paranasal sinus CT revealed no signs of inflammation in the sinuses but suggested bony obstruction of the drainage channel of the frontal sinus. Results: All three patients had recovery from headache, nasal mucosal recovery, and patent frontal sinus drainage. The recurrence rate of forehead tightness and discomfort or pain was 0. Conclusion: Noninflammatory frontal sinus headache does exist. Endoscopic frontal sinus opening surgery is a feasible treatment modality that can largely or even completely eliminate the stuffy swelling and pain in the forehead. The diagnosis and surgical indications for this disease are based on a combination of anatomical abnormalities and clinical symptoms.

New insights on low-temperature storage regulating garlic greening and the accumulation of pigment precursors via glutathione metabolism and energy cycles.

To explore regulation mechanism of temperature on garlic greening and pigment precursors' accumulation, greening capacities, pigment precursors and critical metabolites, enzyme and genes involved in glutathione and NADPH metabolism of garlic stored at five temperatures (4, 8, 16, 24 and 30 ℃) were analyzed. Results showed that garlic pre-stored at 4, 8 and 16 ℃ were more likely to green than ones at 24 and 30 ℃ after pickling. After 25 days, more S-1-propenyl-l-cysteine sulfoxide (1-PeCSO) were detected in garlic stored at 4, 8 and 16 ℃ (753.60, 921.85 and 756.75 mAU, respectively) than that at 24 and 30 ℃ (394.35 and 290.70 mAU). Pigment precursors' accumulation in garlic was mainly realized by glutathione and NADPH metabolism under low-temperature storage, through enhancements of activities or expressions for GR (GSR), GST (GST), γ-GT (GGT1, GGT2), 6PGDH (PGD) and ICDHc (IDH1). This study enriched the mechanism of garlic greening.

Comparative transcriptome and proteome profiles reveal the regulation mechanism of low temperature on garlic greening.

Garlic stored at low temperature (0-13 ℃) for some times and subsequently crushed and placed at room temperature would turn green, while the one stored at high temperature (30 ℃) would not. In order to elucidate the regulatory mechanism of low temperature on garlic greening, transcriptome and proteome profiles of garlic stored at 4 ℃ and 30 ℃ were explored by RNA-seq and iTRAQ techniques. Principal component analysis showed that garlic at different storage temperatures were of significant differences on both gene and protein levels. 14,381 and 861 differential expression genes (DEGs) and proteins (DEPs) were identified respectively, in which 268 factors were shared according to their joint analysis, including 186 (144) up-regulated genes (proteins) and 82 (124) down-regulated genes (proteins) in comparing garlic stored at 4 ℃ with ones at 30 ℃. These 268 factors were mainly attributed to biological process (metabolic process) and molecular function (catalytic activity, binding) categories by Gene Ontology classification. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways enrichment of DEGs and DEPs revealed that GSSG production, GSH degradation, amino acid biosynthesis (cysteine and methionine) and energy metabolism (TCA and HMP cycles) were promoted by low-temperature storage to responding to oxidative stress and prepared for pigment synthesis in garlic. These results provide valuable information for the regulation of garlic greening during processing.

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy-lysosome mediated OCT4A degradation.

Capsaicin (CAP) is a well-known anti-cancer agent. Recently, we reported capsaicin-induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose-dependently decreased the sphere formation capacity of ATC cells. The stemness-inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP-induced OCT4A degradation was reversed by autophagy inhibitors 3-MA and chloroquine, BAPTA-AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium-dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.

Motor Imagery-Based Brain-Computer Interface Combined with Multimodal Feedback to Promote Upper Limb Motor Function after Stroke: A Preliminary Study.

BACKGROUND: Recently, the brain-computer interface (BCI) has seen rapid development, which may promote the recovery of motor function in chronic stroke patients. METHODS: Twelve stroke patients with severe upper limb and hand motor impairment were enrolled and randomly assigned into two groups: motor imagery (MI)-based BCI training with multimodal feedback (BCI group, n = 7) and classical motor imagery training (control group, n = 5). Motor function and electrophysiology were evaluated before and after the intervention. The Fugl-Meyer assessment-upper extremity (FMA-UE) is the primary outcome measure. Secondary outcome measures include an increase in wrist active extension or surface electromyography (the amplitude and cocontraction of extensor carpi radialis during movement), the action research arm test (ARAT), the motor status scale (MSS), and Barthel index (BI). Time-frequency analysis and power spectral analysis were used to reflect the electroencephalogram (EEG) change before and after the intervention. RESULTS: Compared with the baseline, the FMA-UE score increased significantly in the BCI group (p = 0.006). MSS scores improved significantly in both groups, while ARAT did not improve significantly. In addition, before the intervention, all patients could not actively extend their wrists or just had muscle contractions. After the intervention, four patients regained the ability to extend their paretic wrists (two in each group). The amplitude and area under the curve of extensor carpi radialis improved to some extent, but there was no statistical significance between the groups. CONCLUSION: MI-based BCI combined with sensory and visual feedback might improve severe upper limb and hand impairment in chronic stroke patients, showing the potential for application in rehabilitation medicine.

Motor imagery based brain-computer interface control of continuous passive motion for wrist extension recovery in chronic stroke patients.

Motor recovery of wrist and fingers is still a great challenge for chronic stroke survivors. The present study aimed to verify the efficiency of motor imagery based brain-computer interface (BCI) control of continuous passive motion (CPM) in the recovery of wrist extension due to stroke. An observational study was conducted in 26 chronic stroke patients, aged 49.0 ± 15.4 years, with upper extremity motor impairment. All patients showed no wrist extension recovery. A 24-channel highresolution electroencephalogram (EEG) system was used to acquire cortical signal while they were imagining extension of the affected wrist. Then, 20 sessions of BCI-driven CPM training were carried out for 6 weeks. Primary outcome was the increase of active range of motion (ROM) of the affected wrist from the baseline to final evaluation. Improvement of modified Barthel Index, EEG classification and motor imagery pattern of wrist extension were recorded as secondary outcomes. Twenty-one patients finally passed the EEG screening and completed all the BCI-driven CPM trainings. From baseline to the final evaluation, the increase of active ROM of the affected wrists was (24.05 ± 14.46)˚. The increase of modified Barthel Index was 3.10 ± 4.02 points. But no statistical difference was detected between the baseline and final evaluations (P > 0.05). Both EEG classification and motor imagery pattern improved. The present study demonstrated beneficial outcomes of MI-based BCI control of CPM training in motor recovery of wrist extension using motor imagery signal of brain in chronic stroke patients.

Induction of Apoptosis in Human Papillary-Thyroid-Carcinoma BCPAP Cells by Diallyl Trisulfide through Activation of the MAPK Signaling Pathway.

This study aimed to elucidate the potential effects of diallyl trisulfide (DATS) on human papillary-thyroid-carcinoma BCPAP cells and its underlying mechanisms. DATS is an organosulfur compound derived from garlic. In this study, we demonstrated that compared with the solvent control, DATS treatment at concentrations of 5, 10, and 20 µΜ decreased cell survival rates of BCPAP cells to 84.51 ± 2.67, 57.16 ± 1.18, and 41.22 ± 1.19% respectively. DATS also caused cell-cycle arrest at G0/G1 phase, and the proportion of cells arrested in G0/G1 phase rose from 68.8 ± 8.38 to 80.4 ± 8.38%, which eventually resulted in cell apoptosis through a mitochondrial apoptotic pathway in BCPAP cells. Further evidence showed that DATS activated ERK, JNK, and p38, members of the MAPK family. Moreover, ERK and JNK inhibitors partially reversed apoptosis in BCPAP cells induced by DATS treatment. Taken together, our results demonstrated that DATS exerted an apoptosis-inducing effect on papillary-thyroid-cancer cells via activation of the MAPK signaling pathway, which shed light on a prospective therapeutic target for thyroid-cancer treatment.

Simultaneous quantitation of six aconitum alkaloids and three flavonoids in the herb couple of radix aconiti lateralis-radix glycyrrhizae (Fuzi-Gancao) by UHPLC-ESI-MS/MS.

BACKGROUND: Fuzi-Gancao herb couple is one of the commonly used herb couples involved in the traditional Chinese medicine formulations, with radix aconiti lateralis (Fuzi in Chinese) and radix glycyrrhizae (Gancao in Chinese) as a ratio of 1:1. Alkaloids and flavonoids were considered as the main active ingredients of Fuzi-Gancao herb couple. However, no analytical methods have been reported to quantitatively analyze these activity ingredients in Fuzi-Gancao herb couple simultaneously. OBJECTIVE: To develop a simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds, namely, aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconitine (BAC), benzoylmesaconitine (BMA), benzoylhypaconitine (BHA), liquiritin, isoliquiritin, and licochalcone A (LCA) in Fuzi-Gancao herb couple. MATERIALS AND METHODS: The chromatographic separation was achieved using a reversed phase C18 column and a mobile phase consisted of water (0.1% formic acid in water, v/v) and acetonitrile. The detection was achieved in multiple reaction monitoring modes. The optimal mass transition ion pairs (m/z) for quantitation were 646.3/586.5 for AC, 632.4/572.5 for MA, 616.3/556.4 for HA, 604.5/572.5 for BAC, 590.4/540.4 for BMA, 574.1/542.5 for BHA, 419.4/257.1 for liquiritin, 419.4/257.1 for isoliquiritin, and 339.2/121.1 for LCA. RESULTS: Good linearity was observed in validated concentration range for each analyte (r > 0.9992), and the intra- and inter-day precisions were <3.12% and 3.65%, respectively. The recovery ranged from 85.36% to 110.14%. CONCLUSIONS: The results demonstrated that the method developed was reliable, rapid, and specific. Moreover, this method was successfully applied to control the quality of Fuzi-Gancao herb couple. SUMMARY: A simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds in Fuzi-Gancao herb couple has been developed. Abbreviations used: UHPLC-ESI-MS/MS: Ultra High Performance Liquid Chromatography-electrospray ionization-mass spectrometry; RSD: Relative standard deviations; LOD: Limit of detection; LOQ: Limit of quantification; MRM: Multiple reaction monitor; TCMs: Traditional Chinese medicines.

The mechanism underlying proliferation-inhibitory and apoptosis-inducing effects of curcumin on papillary thyroid cancer cells.

Recently, many studies on health benefits associated with curcumin have been reported. In this study, the effects of curcumin on apoptosis of papillary thyroid cancer cell line K1 and its potential mechanisms were investigated. Curcumin was found to significantly inhibit cell viability and promoted cell apoptosis in a dose-dependent manner. Moreover, curcumin-induced cell apoptosis was characterized with a rapid stimulation of reactive oxygen species (ROS) production. Furthermore, curcumin-induced ROS generation led to the loss of mitochondrial membrane potential (MMP) and the disturbance of intracellular Ca(2+) concentration. A decrease in expression of Bcl-2 and the cleavage of poly ADP-ribose polymerase (PARP) were observed after exposure to curcumin. Results of this study may elucidate the curcumin-induced apoptosis effects on K1 cells. Thus, our results indicate a role of curcumin as health-promoting food ingredient, as well as a potential chemotherapeutic agent which is able to fight against papillary thyroid cancer.