Farrerol is a dihydroflavone compound extracted from the dried leaves of Rhododendron dauricum belonging to the Ericaceae family. This article systematically reviews relevant research on farrerol both domestically and internationally， summarizes its pharmacological activities and mechanisms of action， and finds that it exerts cardiovascular and cerebrovascular protective effects by maintaining the homeostasis of vascular endothelial function and inhibiting vascular intimal hyperplasia； exerts renal protective effects by activating the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway to reduce renal damage； exerts liver protective effects by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway， activating the Nrf2 signaling pathway， improving insulin resistance， and reducing lipid deposition in the liver； exerts neuroprotective effects by activating the Nrf2/Keap1 signaling pathway， inhibiting the Toll-like receptor 4 and cyclic GMP-AMP synthase/stimulator of interferon genes signaling pathways to reduce neuroinflammatory damage； exerts bone protective effects by promoting tendon formation and inhibiting osteoclast differentiation； exerts antitumor effects by inducing tumor cell apoptosis and weakening tumor cell invasion and metastasis； and exerts antibacterial effects by downregulating α -toxin expression， interfering with β -lactamase/penicillin-binding protein 2a （PBP2a）， and inhibiting PBP2a oligomerization. Currently， research on the pharmacological effects of farrerol is still mainly focused on animal and cell experiments. Further mechanistic studies and clinical trials are needed to provide theoretical basis for its new drug development and clinical application.

Farrerol is a dihydroflavone compound extracted from the dried leaves of Rhododendron dauricum belonging to the Ericaceae family. This article systematically reviews relevant research on farrerol both domestically and internationally， summarizes its pharmacological activities and mechanisms of action， and finds that it exerts cardiovascular and cerebrovascular protective effects by maintaining the homeostasis of vascular endothelial function and inhibiting vascular intimal hyperplasia； exerts renal protective effects by activating the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway to reduce renal damage； exerts liver protective effects by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway， activating the Nrf2 signaling pathway， improving insulin resistance， and reducing lipid deposition in the liver； exerts neuroprotective effects by activating the Nrf2/Keap1 signaling pathway， inhibiting the Toll-like receptor 4 and cyclic GMP-AMP synthase/stimulator of interferon genes signaling pathways to reduce neuroinflammatory damage； exerts bone protective effects by promoting tendon formation and inhibiting osteoclast differentiation； exerts antitumor effects by inducing tumor cell apoptosis and weakening tumor cell invasion and metastasis； and exerts antibacterial effects by downregulating α -toxin expression， interfering with β -lactamase/penicillin-binding protein 2a （PBP2a）， and inhibiting PBP2a oligomerization. Currently， research on the pharmacological effects of farrerol is still mainly focused on animal and cell experiments. Further mechanistic studies and clinical trials are needed to provide theoretical basis for its new drug development and clinical application.

Objective To explore the potential causal relationship between occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") and five mental disorders (depression, bipolar disorder, schizophrenia, insomnia and anxiety) using the two-sample Mendelian randomization (MR) method. Methods Single nucleotide polymorphisms (SNPs) loci associated with pneumoconiosis and five mental disorders were screened from Genome-Wide Association Studies. Inverse variance weighting (IVW), weighted median (WM) and MR-Egger regression methods were used to evaluate the significance of the causal relationship between pneumoconiosis and five mental disorders. Sensitivity analysis was used to evaluate the accuracy and reliability of the research results. Results After matching data of pneumoconiosis and the five mental disorders, 16 SNPs were ultimately included as instrumental variables in this study. The result of MR analysis revealed a positive causal relationship between pneumoconiosis and both depression [IVW: odds ratio (OR) and 95% confidence interval (CI) was 1.017 (1.000-1.035), P<0.05] and bipolar disorder [IVW: OR(95%CI)was 1.046(1.009-1.083), P<0.05; WM: OR (95%CI) was 1.055(1.007-1.105), P<0.05]. Result of sensitivity analysis indicated there was no heterogeneity and horizontal pleiotropy in the above results. There was no causal association observed between pneumoconiosis and schizophrenia, insomnia, or anxiety disorders (all P>0.05). Conclusion This study provides genetic evidence supporting a positive causal relationship between pneumoconiosis and both depression and bipolar disorder.

Pinelliae Rhizoma (PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean, is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata (Thunb.) Breit. (PT). It is extensively utilized in dispensing granules, classical prescriptions, and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea, asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including PubMed, Web of Science, Scopus, ScienceDirect, Wanfang, and China National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer, anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, anti-microbial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic, learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.
Humans ; Pinellia/chemistry* ; Animals ; Ethnopharmacology ; Drugs, Chinese Herbal/chemistry* ; Phytochemicals/chemistry* ; Rhizome/chemistry*

In the field of healthcare service,it is crucial to optimize medical innovation services by combining the preferences of health service providers and demanders(i.e.,stakeholders).The best-worst scaling(BWS)method is a recently developed stated preference method for assessing preferences with distinctive advantages.Nevertheless,there is a lack of a comprehensive introduction to stakeholder preference assessment using BWS,thus constraining its applications and promotion.This paper introduces the process of using BWS to assess service providers'preferences for the Shared Medical Appointment for diabetes(SMART),an integrated healthcare service of medicine and health management,in the hope of providing reference for researchers for promoting the use of BWS in implementation research.

Objective:To investigate the characteristics of m6A methylation modification patterns in mRNA of patients with major depressive disorder (MDD) and its effect in the pathogenesis of the disease.Methods:From March 2022 to May 2023, five untreated MDD patients were assigned to the MDD group, and five healthy individuals were enrolled as the healthy control group at the First Psychiatric Hospital of Harbin.Microarray analysis was performed to determine the m6A modification profiles and gene expression patterns of mRNA in MDD. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were conducted to elucidate the effect of m6A methylation in the development of depression. Finally, methylated RNA immunoprecipitation combined with quantitative PCR (MeRIP-qPCR) was used to validate the m6A methylation levels of key mRNAs (GRM4, CAMKK2). Data were analyzed using R software (version 4.2.0) with t-test and Fisher's exact test. Results:Significant differences in m6A-modified mRNAs were observed between MDD patients and healthy controls. A total of 513 mRNAs (180 hypermethylated and 333 hypomethylated) exhibited differential m6A modifications in MDD patients. GO and KEGG analysis revealed that hypermethylated mRNAs were primarily enriched in neuroactive ligand-receptor interactions, while hypomethylated mRNAs were associated with the AMP-activated protein kinase (AMPK) signaling pathway. Additionally, a total of 350 differentially expressed mRNAs were identified (171 upregulated and 179 downregulated), enriched in the cyclic adenosine monophosphate (cAMP) and tumor necrosis factor (TNF) signaling pathways. MeRIP-qPCR results demonstrated that the m6A methylation level of GRM4 in MDD patients (25.40±2.38) was significantly higher than that in healthy controls (9.40±1.00) ( t=13.88, P<0.05), whereas the methylation level of CAMKK2 (19.63±6.60) was significantly lower than that in healthy controls (30.51±7.20) ( t=2.48, P<0.05). Conclusion:The m6A modification expression profile is abnormal in patients with major depressive disorder, which may be involved in the pathogenesis and development of MDD, and the identification of key pathways may provide new clues and evidence for the development of more effective therapeutic targets for MDD.

Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

Objective:To investigate the characteristics of m6A methylation modification patterns in mRNA of patients with major depressive disorder (MDD) and its effect in the pathogenesis of the disease.Methods:From March 2022 to May 2023, five untreated MDD patients were assigned to the MDD group, and five healthy individuals were enrolled as the healthy control group at the First Psychiatric Hospital of Harbin.Microarray analysis was performed to determine the m6A modification profiles and gene expression patterns of mRNA in MDD. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were conducted to elucidate the effect of m6A methylation in the development of depression. Finally, methylated RNA immunoprecipitation combined with quantitative PCR (MeRIP-qPCR) was used to validate the m6A methylation levels of key mRNAs (GRM4, CAMKK2). Data were analyzed using R software (version 4.2.0) with t-test and Fisher's exact test. Results:Significant differences in m6A-modified mRNAs were observed between MDD patients and healthy controls. A total of 513 mRNAs (180 hypermethylated and 333 hypomethylated) exhibited differential m6A modifications in MDD patients. GO and KEGG analysis revealed that hypermethylated mRNAs were primarily enriched in neuroactive ligand-receptor interactions, while hypomethylated mRNAs were associated with the AMP-activated protein kinase (AMPK) signaling pathway. Additionally, a total of 350 differentially expressed mRNAs were identified (171 upregulated and 179 downregulated), enriched in the cyclic adenosine monophosphate (cAMP) and tumor necrosis factor (TNF) signaling pathways. MeRIP-qPCR results demonstrated that the m6A methylation level of GRM4 in MDD patients (25.40±2.38) was significantly higher than that in healthy controls (9.40±1.00) ( t=13.88, P<0.05), whereas the methylation level of CAMKK2 (19.63±6.60) was significantly lower than that in healthy controls (30.51±7.20) ( t=2.48, P<0.05). Conclusion:The m6A modification expression profile is abnormal in patients with major depressive disorder, which may be involved in the pathogenesis and development of MDD, and the identification of key pathways may provide new clues and evidence for the development of more effective therapeutic targets for MDD.

Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

AIM: To explore the dynamic expression of high mobility group box 1(HMGB1)in scar tissues after glaucoma drainage valve implantation, and to further reveal the role and possible mechanism of HMGB1 in scarring after glaucoma surgery.METHODS: A total of 60 New Zealand white rabbits were randomly divided into control group(n=20), model group(n=20, silicone implantation under conjunctival sac)and model with drug administration group(n=20, silicone implantation under conjunctival sac combined with 5-fluorouracil injection). The conjunctival tissues were collected at 4 and 8 wk after surgery. HE staining and Masson staining were used to detect the proliferation and distribution of fibroblasts and collagen fibers in conjunctival tissues. Immunohistochemistry was utilized to detect the distribution and changes of HMGB1, transforming growth factor(TGF)-β1, Smad3 and α-smooth muscle actin(SMA)in conjunctival tissues. RT-PCR and Western blot were adopted to detect the mRNA and protein expression of HMGB1, TGF-β1, Smad3 and α-SMA in conjunctival tissues.RESULTS: HE staining and Masson staining showed that the proliferation of inflammatory cells, fibroblasts and collagen fibers in the model group was significantly higher than that in the control group at both 4 and 8 wk. Meanwhile, the proliferation of fibroblasts and collagen fibers in the model with drug administration group was significantly lower than that in the model group. Immunohistochemical staining showed that the expression of HMGB1, TGF-β1, Smad3 and α-SMA protein was observed in the conjunctival tissues of the model group both 4 and 8 wk, with brown and significantly deeper staining of the model group at 8 wk. Meanwhile, the positive staining in the model with drug administration group at both 4 and 8 wk was significantly lower than that in the model group. There was positive correlations between the number of fibroblasts stained with HE and the expression of HMGB1 in the conjunctival tissue of the model group at both 4 and 8 wk(r=0.602, 0.703, all P<0.05). RT-PCR and Western blot revealed that the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model group were significantly higher than those in the control group at both 4 and 8 wk(all P<0.05). Meanwhile, the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model with drug administration group were significantly lower than those in the model group(all P<0.05). There was positive correlations between mRNA expressions of HMGB1 and TGF-β1, Smad3 in the model group and the model with drug administration group(all P<0.05).CONCLUSION: The expression of HMGB1 increased at a time-dependent manner after glaucoma valve implantation. HMGB1 acts an indispensable role in the initiation and progression of scar formation after glaucoma surgery, which may be involved in the regulation of TGF-β/Smad signaling pathway.