This article discussed the evolution of the traditional preparation process of Pinelliae Rhizoma Fermentata.The production methods for Pinelliae Rhizoma Fermentata in Song Dynasty include cake-making of Pinelliae Rhizoma together with ginger juice and fermentation after cake-making,and the former method of cake-making was the mainstream.The process technology in Jin and Yuan Dynasties inherited from that in Song Dynasty,and the application of Pinelliae Rhizoma Fermentata had certain limitations.The medical practitioners of Ming Dynasty elucidated the mechanism of processing of Pinelliae Rhizoma Fermentata,and proposed the view of"sliced Pinelliae Rhizoma being potent while fermented Pinelliae Rhizoma being mild".In the Ming Dynasty,LI Shi-Zhen defined the cake-making process and fermentation process for Pinelliae Rhizoma,and HAN Mao's Han Shi Yi Tong(Han's Clear View of Medicine)contained five prescriptions for the processing of Pinelliae Rhizoma Fermentata,which had the epoch-making signficance in the expansion of prescriptions for the processing of Pinelliae Rhizoma Fermentata.In the Qing Dynasty,HAN Fei-Xia's ten methods for making Pinelliae Rhizoma Fermentata were summarized on the basis of the methods recorded in Han Shi Yi Tong,and at that time,the processing of Pinelliae Rhizoma Fermentata and the preparation of Massa Medicata Fermentata interacted with each other.After the founding of the People's Republic of China,the local experience in the preparation of Pinelliae Rhizoma Fermentata was deeply influenced by the methods in the Qing Dynasty,and the local preparation technical standards gradually became the same.Moreover,this article also explored the issues of the importance of"Pinelliae Rhizoma"and"ingredients for fermentation",the pre-treatment of Pinelliae Rhizoma,the distinction between cake-making process and fermentation process for Pinelliae Rhizoma,the amount of flour added as well as the timing of adding,the addition of Massa Medicata Fermentata powder,the role of Alum in Pinelliae Rhizoma Fermentata and so on.

ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.
Antioxidants/chemistry* ; Molecular Docking Simulation ; Artemisia ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Anti-Inflammatory Agents/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aβ injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.
Humans ; Dementia, Vascular/drug therapy* ; Vascular Endothelial Growth Factor A ; NF-kappa B/metabolism* ; Antioxidants ; Brain Ischemia ; Cholinergic Agents

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

AIM To study the secondary metabolites from symbiotic fungi Talaromyces amestolkiae of Syngnathus acus Linnaeus.METHODS The methanol extract from Talaromyces amestolkiae fermentation was isolated and purified by silica gel,Sephadex LH-20,TLC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Ten compounds were isolated and identified as 2,4-bis(1,1-dimethylethyl)benzeneethanol(1),aspergillumarins A(2),peniciisocoumarins H(3),2-(2-hydroxypropyl)-5-methyl-7-hydroxychromone(4),6-demethylvermistatin(5),penicimarin B(6),penicimarin C(7),8-hydroxy-6-methoxy-3-methylisocoumarin(8),polygonolide(9),ganoderpurine(10).CONCLUSION Compound 1 is a new natural product.Compounds 3-5,8-10 are isolated from this fungi for the first time.

Objective: To examine the effect of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) for atherosclerotic lesions in no-stenting zones (NSZ) of the lower extremity. Methods: From June 2019 to December 2021, 46 patients who underwent ELA combining with DCB in lesions of NSZ at Zhongshan Hospital, Fudan University and Jinshan Hospital, Fudan University were retrospectively enrolled, including 29 males and 17 females. The age was (72.5±11.7) years (range: 42 to 93 years). Among them, 44 lesions (95.7%, 44/46) were in popliteal artery and 2 lesions (4.3%, 2/46) were in common femoral artery. Chronic total occlusion (CTO) was observed in 31 patients (76.4%, 31/46), and stenotic lesions were observed in 15 patients (32.6%, 15/46). The length of lesions was (7.3±2.7) cm (range: 3.0 to 13.2 cm). Patients were followed at 6, 12 months after surgery and every year thereafter, and they underwent Doppler and CT angiography examination at each follow-up point. The primary endpoint was primary patency. The secondary endpoints included major amputation-free survival (MAFS) rate, technical success, bailout stent, ankle-brachial index (ABI), target lesion reintervention (TLR). Student t test was applied to compare the difference between ABI of 6 or 12 months after surgery and the baseline. Primary patency, freedom from TLR, and MAFS rate were calculated by Kaplan-Meier method. Results: The technical success rate was 91.3% (42/46). The rate of procedure-related complication was 6.5% (3/46), and all the complications were distal embolization. The rate of flow-limiting dissection was 8.7% (4/46). ABI was significantly increased at 6 and 12 months compared to preoperatively (0.90±0.10 vs. 0.42±0.10, t=-4.48, P<0.01; 0.87±0.12 vs. 0.42±0.10, t=-5.21, P<0.01). The follow-up time[M(IQR)] was 22.5 (8.8) months (range: 6 to 32 months). TLR was performed in 4 patients (4/46, 8.7%). The 2-year primary patency was 86.2% (95%CI: 71.8% to 93.5%). The 2-year freedom from TLR and MAFS rate were 90.7% (95%CI: 77.0% to 96.4%) and 97.8% (95%CI: 85.6% to 99.7%), respectively. Conclusion: ELA combining with DCB can be applied to treat atherosclerotic lesions in NSZ.
Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Arteries ; Laser Therapy

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) μg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.
Animals ; Capsules ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry/methods*