In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals ; Cannabidiol/administration & dosage* ; Polyglutamic Acid/analogs & derivatives* ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Anti-Inflammatory Agents/administration & dosage* ; Micelles ; Caco-2 Cells ; Cholesterol/pharmacokinetics* ; Tissue Distribution ; Nanoparticles/chemistry*

A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L^-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
Withanolides/isolation & purification* ; Physalis/chemistry* ; Humans ; Molecular Structure ; Cell Line, Tumor ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Cell Proliferation/drug effects* ; Plant Leaves/chemistry* ; Plant Extracts/pharmacology*

AIM:To construct a recombinant adenovirus vector carrying the mouse ubiquitin-like with plant homeodomain and RING finger domains 1(Uhrf1)gene,validate the expression of Uhrf1 in neonatal mouse cardiomyo-cytes and explored its role in hydrogen peroxide(H2O2)-induced DNA damage.METHODS:The mouse Uhrf1 gene cod-ing sequence was amplified by polymerase chain reaction(PCR),digested,and inserted into the pADM-CMV-C-FH vec-tor to create the recombinant adenoviral plasmid ADM-Uhrf1.Following transfection into HEK293T cells,we generated re-combinant adenoviral particles,amplified,purified,and determined the titer.Neonatal mouse cardiomyocytes were infect-ed at an multiplicity of infection(MOI)of 50,UHRF1 protein expression was validated via Western blot and immunofluo-rescence staining.H2O2-induced DNA damage was explored along with adenovirus-mediated Uhrf1 overexpression to inves-tigate its role in DNA damage repair.RESULTS:ADM-Uhrf1 virus titer,determined by capsid immunofluorescence as-say,was 1.8×1013 pfu/L.Western blot confirmed a significant increase in UHRF1 protein expression(P＜0.05),with im-munofluorescence indicating predominant nuclear localization.Uhrf1 overexpression effectively inhibited the expression of the DNA damage marker,phosphorylated H2AX protein(γH2AX)(P＜0.01).CONCLUSION:We successfully con-structed a recombinant adenoviral vector carrying the mouse Uhrf1 gene,facilitating Uhrf1 overexpression in neonatal mouse cardiomyocytes.Furthermore,this overexpression effectively alleviated DNA damage in cardiomyocytes.

Objective:To discuss the clinical efficacy of treating lumbar muscle strain(LMS)with Tuina(Chinese therapeutic massage)plus Chinese medication hot compress. Methods:A total of 147 LMS patients were randomized into a Tuina group,a Chinese medication hot compress group,and a combined group,each consisting of 49 cases.The Tuina group received Tuina treatment;the Chinese medication hot compress group received Chinese medication hot compress treatment;and the combined group received the forementioned two therapies alternately.The three groups of patients were assessed using the visual analog scale(VAS)and Oswestry disability index(ODI)before treatment and after 2 weeks of treatment.A 2-month follow-up was also conducted to observe the relapse rate. Results:The VAS and ODI scores dropped significantly after treatment in all three groups compared with their baseline(P<0.05),and the combined group surpassed the other two groups in comparing the ODI score(P<0.05).The 2-month follow-up showed that the combined group had the lowest relapse rate among the three groups(P<0.05). Conclusion:Compared to each therapy used alone,Tuina plus Chinese medication hot compress can relieve pain,improve daily living function,and reduce the short-term relapse rate better in treating LMS patients.

Objective:To observe the clinical efficacy of neck Gongfa exercise in intervening people at high risk for cervical spondylosis. Methods:A total of 212 participants from 8 companies at high risk for cervical spondylosis were divided into two groups using the random number table method,with 105 participants in the control group receiving health education and 107 participants in the trial group receiving an additional neck Gongfa exercise.After successive 3-month interventions,the two groups were compared in terms of cervical soft tissue tension and neck disability index(NDI)score.The incidence of cervical spondylosis was observed 3 months later. Results:During the process,10 cases dropped out in the trial group,and the control group had 9 dropout cases.After the intervention,the cervical soft tissue tension value and NDI score improved in both groups(P<0.05)and showed significant differences between the two groups(P<0.05).At the 3-month follow-up,the trial group had a lower incidence rate of cervical spondylosis than the control group(P<0.05). Conclusion:For people at high risk for cervical spondylosis,neck Gongfa exercise can effectively improve cervical soft tissue tension and motor dysfunction and lower the incidence of cervical spondylosis in the short run.

The microsphere drug delivery systems have been extensively exploited for providing controllable drug release kinetics, enhancing drug stability and localized drug delivery. In past decade, dozens of microsphere drug delivery systems have been developed for clinical therapy of cancer, schizophrenia and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinsonism). In this review article, we comprehensively summarized the fabrication methods of drug delivery systems and highlighted their advances for clinical application. Furthermore, we analyzed the potential and the challenges for clinical translation of the drug delivery systems.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Proanthocyanidin (PA), as a kind of natural plant polyphenol, have a variety of biological functions, such as promoting remineralization, inducing collagen cross-linking, inhibiting protease activity and inhibiting bacteria. Therefore, PA could be broadly used in the clinical application of treatment and repair of deep caries in the future; for example, PA could promote dentin remineralization, improve resin-dentin bonding durability and improve the dentin acid erosion effect. This application potential of PA arises from several features, firstly, PA can not only promote dentin remineralization on its own or with other remineralizers but also exhibits antibacterial effects, which can inhibit acid production while reducing the formation of cariogenic pathogens and their biofilms. Based on the above features, PA can reduce the incidence of caries disease; thus, PA improves deep caries and long-term effects after treatment. In addition, PA added to adhesives or etch agents can improve the etching and bonding effect of dentin by inducing collagen cross-linking and inhibiting protease activity, thus achieving the ultimate goal of improving the bonding performance of deep caries. This paper summarizes recent progress of research on PA for the treatment and repair of deep caries, including the promotion of dentin remineralization and antibacterial activity as well as the improvement in dentin bonding and acid etching effect, to provide a more comprehensive reference for treating and restoring deep caries in clinical practice.