OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform， and to evaluate the effectiveness of the reform， thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis， the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment， training， assessment， and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency， with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform， the new training system and model became increasingly mature. In both 2023 and 2024， the participants achieved relatively high average total scores in their initial completion assessments [with scores of （84.05± 5.83） and （85.82±4.35） points， respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of （4.80±0.44） and （4.85±0.39） points， respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future， clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase， while aligning with global trends in pharmacy education and industry development. Additionally， sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.

OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease （CKD）. METHODS Fifty male SD rats were randomly divided into a sham surgery group （10 rats） and a modeling group （40 rats）. The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling， the rats were randomly divided into model group， esaxerenone group （positive control）， and TCM low- and high-dose groups， with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone， while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively， the sham surgery group and model group were given an equal volume of physiological saline， all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea （SUr）， serum creatinine （SCr）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels； enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α（TNF-α）； immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α） ， mitochondrial transcription factor A （TFAM）， absent in melanoma 2（AIM2）， caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in renal tissue； real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group， the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction， severe tubular dilation， and increased deposition of blue fibrin； the levels of SUr， SCr， MDA， IL-1β， IL-6， TNF-α，the protein expression of AIM2， GSDMD， caspase-1， IL-1β， IL-18 ， and the mRNA expression of AIM2 were significantly increased or up-regulated （P＜0.01）； the levels of SOD， the protein expression of PGC-1α， TFAM were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function， alleviate renal inflammatory damage and pyroptosis， and exert renal protective effects by regulating the AIM2 pyroptosis pathway.

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL^-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g^-1) and jaceosidin (4.17 ± 0.18 mg·g^-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).
Antifungal Agents/chemistry* ; Arthrodermataceae ; Artemisia/chemistry* ; Molecular Docking Simulation ; Mitochondria ; Microbial Sensitivity Tests

Objective To investigate the effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells.Methods MDA-MB-231 breast cancer cells were inoculated on the culture plate for 24h and randomly divided into 8 groups:Control group(C),ropivacaine 400μg/ml group(R),morphine 3μg/ml group(LM),morphine 30μg/ml group(MM),morphine 300μg/ml group(HM),ropivacaine 400μg/ml group+ morphine 3μg/ml group(R+LM),ropivacaine 400μg/ml+ morphine 30μg/ml group(R+MM),and ropivacaine 400μg/ml+ morphine 300μg/ml group(R+HM).After treaments of MDA-MB-231 breast cancer cells for 24h,these proliferation,migration,invasion and cell cycle were evaluated.Results When using morphine alone,the proliferation inhibitive effect was positively correlated with the concentration of morphine.The proliferation was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the proliferation was significantly inhibited(P<0.05).When using morphine combined with ropivacaine,the high concentration morphine group has a synergistic effect with ropivacaine group on proliferation inhibition(P<0.05).When using morphine alone,the migration rate decreases sequentially with the increase of morphine concentration.The migration rate was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the migration rate was inhibited(P<0.05).When using morphine combined with ropivacaine,the low and medium concentration morphine group have a synergistic effect with ropivacaine group on migration rate(P<0.05).When using morphine alone,the number of cell invasion was decreased with the concentration of morphine increasing(P<0.05).The MM and HM groups inhibited cell invasion ability.When using ropivacaine alone,the invasiveness of cells was also inhibited(P<0.05).When using morphine combined with ropivacaine,the medium and high concentration morphine groups have a synergistic effect with ropivacaine group on inhibiting cell invasion ability(P<0.05).When using morphine alone,the cell cycle progression was inhibited into G2/M Phase(P<0.05).When using ropivacaine alone,the cell cycle progression was inhibited into G2/M phase(P<0.05).The combination of low concentration morphine and ropivacaine has synergistic effect on arresting at G0/G1 and S phase(P<0.05).Conclusion Morphine combined with ropivacaine inhibits the Proliferation,migration and invasion of MDA-MB-231 breast cancer cells in a dose-dependent manner.

BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.

Implementation strategies are targeted interventions aimed at promoting the adoption, implementation, and sustainment of research findings or evidence-based practices in routine healthcare. If implementation strategies can precisely match implementation barriers and facilitators, the likelihood of successful implementation will increase. The CFIR-ERIC matching tool, which can match corresponding ERIC implementation strategies based on CFIR barriers, is a convenient and direct tool for developing implementation strategies. This paper provides a detailed overview of the origins and development of the CFIR-ERIC matching tool, outlines its contents and usage, and illustrates how to apply the tool to develop implementation strategies by using a brief smoking cessation intervention project as an example. The paper also discusses the advantages and limitations of using this tool for developing implementation strategies, with the aim of providing methodological reference for other researchers.

Background::Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’ clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.Methods::We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results::We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014). Conclusions::Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.Trial Registration::ClinicalTrials. gov, NCT01670695.

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120-/-)and THP-1 cells. Method Six-eight-week-old C6orf120-/-and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors. Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68+CD86+M1 macrophages from the liver and spleen in the C6orf120-/-rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68+CD80+M1 macrophages and inhibited the CD68+CD206+M2 phenotype. Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120-/-rats.

Objective To investigate the expression and clinical significance of extracellular nicotinamide phosphate ribose transferase(eNAMPT)and soluble programmed death ligand 1(sPD-L1)in serum of pa-tients with sepsis secondary to severe pancreatitis(SAP).Methods A total of 92 SAP patients admitted to the hospital from February 2019 to February 2022 were selected as(SAP grou),and divided into a sepsis group(42 cases)and a non-sepsis group(50 cases).Moreover,50 patients with mild to moderate pancreatitis who were diagnosed and treated at the same time were selected as the disease control group,and 50 healthy in-dividuals who underwent the physical examination in the hospital during the same pariod were selected as the healthy control group.Enzyme linked immunosorbent assay was used to detect serum levels of eNAMPT and sPD-L1.Pearson correlation analysis was used for correlation analysis.Multivariate Logistic regression analy-sis was used to analyze factors affecting the occurrence of secondary sepsis in SAP.The predictive value of ser-um eNAMPT,sPD-L1 and their combination in the secondary sepsis of SAP was conducted by receiver operat-ing characteristic(ROC)curve.Results The serum levels of eNAMPT and sPD-L1 in the SAP group were higher than those in the disease control group and the healthy control group,and the differences were statisti-cally significant(P＜0.05).The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,Sequential Organ Failure Assessment(SOFA)score,white blood cell count,C-reactive protein,pancreatic nec-rosis,systemic inflammatory response syndrome,multiple organ failure,serum eNAMPT and sPD-L1 in the sepsis group were higher than those in the non-sepsis group,and the differences were statistically significant(P＜0.05).There was a positive correlation between serum eNAMPT,sPD-L1 and APACHE Ⅱ score,SOFA score in sepsis SAP patients(P＜0.05).Serum eNAMPT and sPD-L1 were independent risk factors for sec-ondary sepsis in SAP patients.The area under the curve(AUC)of the combination of serum eNAMPT and sPD-L1 for predicting secondary sepsis in SAP patients was 0.916(95％CI:0.868-0.947),which was signif-icantly larger than 0.846(95％CI:0.791-0.879)and 0.830(95％CI:0.774-0.861)of the single indicator detections,and the differences were statistically significant(Z=4.129,4.885,P＜0.001).Conclusion The serum eNAMPT and sPD-L1 levels in patients with sepsis secondary to SAP are elevated,which are related to the severity of the disease.The combination of serum eNAMPT and sPD-L1 has high predictive value for sec-ondary sepsis in SAP.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.