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.

Objective: To explore the relationship between socio ecological risk factors (SERF), physical activity (PA) developmental trajectories, and depressive symptoms among junior and senior high school students in Tianjin, in order to provide theoretical support for comprehensive interventions for adolescent depression. Methods: A longitudinal follow up design was adopted. In September 2022, a baseline survey was conducted using a stratified cluster random sampling method in two junior high schools and two senior high schools in Tianjin, collecting data on students basic information, SERF, PA, and depressive symptoms. Two follow up surveys were conducted in September 2023 and 2024, yielding 588 valid participants. Latent class growth analysis (LCGA) was used to identify PA developmental trajectory categories among junior and senior high school students. Logistic regression was applied to examine the associations between depressive symptoms and SERF as well as PA trajectories. Results: The detection rates of depressive symptoms among Tianjin junior and senior high school students over the three years were 26.53%, 20.24%, and 21.26 %, respectively. Depressive symptoms were positively correlated with SERF ( OR=1.04, 95%CI=1.03-1.05, P <0.05). The highest risks were observed in the individual dimension and family dimension ( OR =1.28, 1.21, both P <0.05). LCGA identified three PA trajectory groups:persistently low level (80.65%), persistently high level (4.58%), and slowly increasing group ( 14.77 %). Multivariate regression analysis showed that compared with the persistently low level PA, the slowly increasing PA significantly reduced the risk of depressive symptoms ( OR=0.44, 95%CI =0.20-0.88), while SERF still increased the risk of depressive symptoms ( OR=1.04, 95%CI =1.03-1.05) (both P <0.05). Conclusion SERF are risk factors for depression symptoms among junior and senior high school students, whereas slowly increasing PA development trajectory demonstrates a protective effect.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.

Cancer ranks as the second leading cause of death globally and has surpassed cardiovascular diseases to become the primary cause of mortality in developed countries. Cancer stem cells (CSCs), which play crucial roles in cancer recurrence, metastasis, and drug resistance, have attracted significant attention in targeted therapeutic strategies. Aptamers, with unique three-dimensional structures capable of specifically recognizing the surface markers of CSCs, show promising potential in targeted drug delivery systems. Compared with conventional antibodies, aptamers are praised for small molecular weights, low production costs, and easy chemical modification. This review systematically summarizes recent advances in aptamer research targeting the surface markers of CSCs, with particular emphasis on aptamer-drug conjugate systems targeting the markers including EpCAM, CD133, CD44, and ABCG2. Both in vitro cellular studies and in vivo animal models have demonstrated the definite anti-cancer efficacy of aptamer-based drug delivery systems, which are of great significance to develop novel therapeutic strategies and improving the therapeutic effects of CSC-targeted treatment. Thus, aptamer-based drug delivery system has broad application prospects in the field of precise cancer treatment.
Humans ; Neoplastic Stem Cells/metabolism* ; Aptamers, Nucleotide/therapeutic use* ; Drug Delivery Systems/methods* ; Neoplasms/drug therapy* ; Biomarkers, Tumor/metabolism* ; Animals ; Epithelial Cell Adhesion Molecule ; AC133 Antigen ; Hyaluronan Receptors

Objective To observe the therapeutic effect of Qiwei Tangmaishu capsules on type 2 diabetes mice,and explore the mechanisms of its treatment of type 2 diabetes based on network pharmacology.Methods TCMSP,ETCM databases were used to query all components and of Qiwei Tangmaishu capsules and their targets.OMIM and DrugBank databases were used to search for targets of type 2 diabetes.The targets of type 2 diabetes and Qiwei Tangmaishu capsules were intersected by Venny 2.1.0.to perform GO and KEGG pathway enrichment analysis on those intersecting targets using the Metascape website.Then,a mouse model of type 2 diabetes was established,and Qiwei Tangmaishu capsules were given to low,medium,and high dose groups(234,468,and 936 mg/kg,respectively),and metformin(MET)group(200 mg/kg)for 2 weeks.The weight of each mouse was measured before and after treatment,and fasting blood glucose was also measured.After the 2 weeks,fasting insulin was measured;ELISA was used to detect levels of inflammatory factors IL-1β,TNF-α,IL-6,TLR4,and NF-κB in serum;Hematoxylin eosin staining was used to observe the morphology of pancreatic islets;and Caspase 3 and INS immunofluorescence were used to detect apoptosis of pancreatic islet cells and the number of pancreatic beta cells.Western Blot assay was used to detect the expression levels of pancreatic tissue proteins such as p-Akt,Akt,p-PI3K,PI3K,Bax,Bcl2.Results 1260 active ingredient targets were identified in Qiwei Tangmaishu capsules;1205 targets of type 2 diabetes were found.Of these,312 targets were intersected by Venny,with core targets involving Akt1,TNF,IL-6,TLR4,among others.Enrichment analysis identified 240 KEGG pathways,among which"insulin resistance""PI3K/Akt signaling pathway"were the key pathways enriched.The animal experiment result showed that compared with the model group,the intervention of Qiwei Tangmaishu capsules and metformin significantly improved blood glucose and insulin resistance;the content of inflammatory factors in serum decreased,and the apoptosis rate of pancreatic islet cells significantly decreased;the number of pancreatic beta cells significantly increased;the expression of pro-apoptotic protein Bax decreased,the expression of anti-apoptotic protein Bcl2 significantly increased,and the expression of p-PI3K and p-Akt was upregulated.Conclusions Qiwei Tangmaishu capsules can significantly reduce blood glucose levels,restore insulin sensitivity,and reduce islet cell apoptosis in type 2 diabetic mice.The mechanism may be related to the activation of the PI3K/Akt signaling pathway.

To verify whether the two B-cell epitopes Pep1 and Pep4 in the FAdV-4 WZ fiber can be used as candidate epitopes for multivalent epitope vaccines,epitopes Pep1 and Pep4 were tandemly linked with the chicken infectious bronchitis virus strain M41 S1 protein gene in different patterns,and a recombinant fusion plasmid was constructed and expressed in E.coli BL21(DE3).It was confirmed by Western blot and ELISA tests that all four expressed fusion proteins reacted specific-ally with anti-M41 whole virus serum and WZ strain anti-Fiber 2-knob protein serum.After purifi-cation and immunization of BALB/c mice,specific antibodies against the peptide epitopes were de-tected in mouse sera.The results showed that the Pep4 epitope induced a stronger immune re-sponse than the Pep1 epitope.When Pep1 was connected with the amino and carboxyl termini of the fusion protein,respectively,both resulted in the production of the same level of anti-Pep1 anti-bodies in the immunized animals,whereas when Pep4 was connected with the carboxyl terminus of the fusion protein,the immunized animals produced a higher level of anti-Pep4-specific antibodies.This research indicates that the B cell epitopes Pep1 and Pep4 of the reactive WZ strain Fiber 2,when conjugated with proteins to form fusion proteins,can enhance the immunogenicity of Pep1 and Pep4 without affecting the antigenicity of the carrier protein.This study provides technical support and serves as a reference for the design and development of a multivalent epitope vaccine for FAdV-4.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.