The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Aim To investigate the antagonistic effect of Schizandrin A(SchA)on oxidative stress-induced endothelial dysfunction and its mechanism of action.Methods Human umbilical vein endothelial cells(HUVECs)were selected as the research subjects,and the effects of SchA on cell viability were detected by MTT assay;the content of ROS in the cells was detec-ted by flow cytometry;the content of MDA and CAT in the cells,and the content of NO and ET-1 in the cell supernatant were detected by kit assay;and the expres-sion of SOD1,p-eNOS/eNOS proteins,and ET-1 in the cell supernatant were detected by Western blot.Immu-nofluorescence experiments were performed to detect Nrf2 entry into the nucleus of cells.Results SchA re-versed the LPS-or hypoxia-induced increase in ROS and MDA content as well as the decrease in SOD1 and CAT content in HUVECs by activating the Nrf2/Keap1/HO-1 signaling pathway.SchA inhibited the decrease of p-eNOS and eNOS protein expression in HUVECs cells,as well as NO content in cell culture medium and the increase of ET-1 content induced by LPS.The Nrf2 inhibitor ML385 reversed the antagonis-tic effects of SchA on oxidative stress and endothelial dysfunction.Conclusions SchA antagonized LPS and hypoxia-induced oxidative stress,and SchA amelio-rated oxidative stress-induced endothelial dysfunction by up-regulating the Nrf2/Keap1/HO-1 signaling path-way.

Rheumatoid arthritis(RA)is a chronic,systemic,autoimmune inflammatory disease.Bone destruction caused by RA is a key factor in disability,involving abnormal activation of immune cells,overproduction of inflammatory factors,and imbalances in bone remodeling process.Ferroptosis,a form of cell death associated with disturbed iron metabolism,inactivation of the antioxidant system and lipid peroxidation,plays a complex role in RA bone destruction.Traditional Chinese medicine(TCM),with its multi-targeted intervention properties,has shown significant potential and advantages in treatment of RA bone destruction.A variety of TCM can regulate the ferroptosis pathway and influence osteoblast function,which has an important role in slowing down RA bone destruction.This review focuses on the latest research progress in the regulation of ferroptosis pathway by TCM to alleviate RA bone destruction,aiming to provide new perspectives and theoretical basis for the treatment of RA bone destruction.

Objective:To investigate the trends in insulin resistance, as represented by the triglyceride-glucose index (TyG index), among Chinese adult residents from 2010 to 2018 and to explore influencing factors.Methods:China Chronic Disease and Risk Factor Surveillance was conducted in 2010, 2013, and 2018, using a multi-stage stratified cluster random sampling method across all 31 provinces (autonomous regions and municipalities) in China. This study sampled 98 712 adults in 2010, 176 534 adults in 2013, and 184 876 adults in 2018, all aged ≥18 years, totaling 406 933 participants. Individuals with a TyG index > P75 were classified as having insulin resistance. The mean TyG index and the prevalence of insulin resistance were calculated for different years, sexes, age groups, provinces (autonomous regions and municipalities), and subgroups for 2018. Linear and logistic regression models were used to test trends in means and rates over time, and multivariate logistic regression models were conducted to analyze potential factors associated with insulin resistance. All analyses were adjusted for complex sampling weights based on the study design. Results:From 2010 to 2018, the mean TyG index among Chinese adults increased from 8.44±0.63 to 8.70±0.64, with significant upward trends observed across different age groups, sexes, and urban-rural residencies (all P<0.001). The mean TyG index was higher among males, urban residents, and those aged 45-59. There were significant differences in the mean TyG indices and prevalence of insulin resistance across provinces (autonomous regions and municipalities) (all P<0.05). Higher insulin resistance prevalence was independently associated with being male, aged ≥45 years, living in urban areas, excessive alcohol consumption, and insufficient physical activity (all P<0.05). Conclusions:From 2010 to 2018, the level of insulin resistance, as indicated by the TyG index, showed an increasing trend among Chinese adults. Males, individuals aged ≥45 years, urban residents, and individuals with unhealthy lifestyles such as excessive alcohol consumption or insufficient physical activity should be the focus of efforts to prevent and control metabolic diseases related to insulin resistance.

Objective To explore the biosynthesis of Dipsacus asper Wall.ex Henry triterpenoid saponin,and the UGT gene in Dipsacus asper Wall.ex Henry has been analyzed by the identification of whole genome,genome and prokaryotic expression.Methods The laboratory self-tested sequenced protein sequence files of the Dipsacus asper Wall.ex Henry genome were used.To validate the conserved domains of the sequence of the Dipsacus asper Wall.ex Henry UGT gene,BLASTP and hmmsearch were utilized.Prot-Param,SOMPA,MAGA7.0,Tbtools and other tools were used to investigate the protein physicochemical properties,protein structure,and covariance analysis of the Dipsacus asper Wall.ex Henry UGT gene family,and using the joint analysis of transcriptomic data and metabolomics data,two glycosyltransferases that might be related to triterpene saponin biosynthesis were screened,and expression vectors were constructed for prokaryotic expression.Results 44 Dipsacus asper Wall.ex Henry UGT genes were identified from the Dipsacus asper Wall.ex Henry genome.The length of Dipsacus asper Wall.ex Henry UGT proteins ranged from 49 to 1083 amino acids,with an average molecular weight of 24.86 kDa and an isoelectric point of 4.31-8.59.Dipsacus asper Wall.ex Henry UGT gene family was distributed on eight chromosomes.The phylogenetic tree constructed from the sequences of Dipsacus asper Wall.ex Henry,Arabidopsis thaliana and identified UGTs showed that glycosyltransferase gene families in Dipsacus asper Wall.ex Henry were mainly in the UGT73,UGT81,UGT85,and UGT80 families.Cis-acting element analysis showed that light-responsive elements were the most prevalent elements in the promoter regions of UGT gene family members.Two glycosyltransferases potentially related to triterpene saponin biosynthesis were screened using combined transcriptomics and metabolomics analysis,and were successfully expressed in prokaryotic form.Conclusion In this study,two candidate genes related to the biosynthesis of Dipsacus asper Wall.ex Henry triterpenoid saponins were jointly screened for prokaryotic expression using multi-omics,and were subjected to prokaryotic expression for further validation of the function of the genes.

In order to comprehensively deepen the reform of medical insurance payment methods and explore the establishment of a medical insurance payment system with Chinese features,five representative cities have been selected for analysis:Jinhua City in Zhejiang Province,Xiamen City in Fujian Province,Suixi City in Anhui Province,TianjinCity,and Zhenjiang City in Jiangsu Province.These regions have been chosen due to their typical ambulatory care payment reform.It summarises the features of ambulatory care payment reforms in different regions regarding implementing agencies,covered crowds and types of illnesses,and payment methods.It is recommended that a reasonable scope of implementation be selected and the reform purpose and basic conditions should be taken into account to explore an appropriate ambulatory care payment reform.It is proposed that an innovative payment method reform be implemented to promote healthcare and prevention integration,and to incorporate a value-oriented paradigm,thereby realizing the benefits of the doctor and patient insurance.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.