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.

ObjectiveTo sort out the pre-ethical review status of drug clinical trials in a tertiary A hospital， summarize practical experience， and provide references for pre-ethical review. MethodA retrospective analysis was conducted on the ethical review of pre-ethical projects in a tertiary A hospital from 2018 to 2023. ResultsFrom 2018 to 2023， a total of 285 pre-ethical projects were reviewed in this tertiary hospital， including 79 projects where it served as the leading unit. Among these， 279 clinical trials ultimately received approval of the ethical review committee， while 6 projects were not approved due to sponsors’ refusal to modify study protocols. In terms of trial phases， phase III clinical trials constituted the largest proportion， and the oncology center was the department with the highest number of projects. In 2023， the average time for pre-ethical review projects from submission to approval was 43 calendar days， 3 days longer than for other project types. In 2023， this hospital reviewed 75 pre-ethical review projects， including 58 where it served as a participating unit. Among these， 42 projects received approval later than the leading unit， while 9 projects were approved earlier than the leading unit’s ethical approval date. Among the pre-ethical review projects applied in 2023， 70 projects obtained drug clinical trial notifications from the National Medical Products Administration， while 5 projects had unknown notification status due to the lack of ethical approval or discontinuation. Of the projects receiving approval notifications， 16 were annotated with matters requiring enhanced attention during clinical trials， and 7 necessitated protocol improvements. ConclusionThis tertiary A hospital has implemented multiple measures to optimize the management of pre-ethical review. This ethical review model does not compromise the quality of ethical review and contributes to accelerating the initiation of clinical trials. Notably， it is crucial to construct a patient-centered drug development system. Clinical trials guided by this concept align with ethical values， laying the foundation for the smooth conduct of clinical trials， assisting in the drug development process， and safeguarding patients’ medication needs.

Despite of the widespread use of hydrogen and methane breath test, the variability in testing protocols, gas measurement techniques, and interpretation criteria continues to challenge the reproducibility and comparability across centers, especially in the Asia-Pacific region. The Asian Neurogastroenterology and Motility Association hence presents the first Asian monograph guiding application and interpretation of breath test. The monograph was formulated according to the framework of indications, preparatory process, performance, and interpretation of results, as well as future direction for research.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

Objective To explore the feasibility and image quality of respiratory-gated total-body ¹⁸F-FDG PET/CT imaging with a 4-minute acquisition in patients with malignant tumors. Methods Sixty-two patients with pathologically confirmed malignant tumors (118 lesions measured) who underwent total-body ¹⁸F-FDG PET/CT examination were consecutively enrolled at the Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, from September 23, 2021 to November 23, 2021, and their clinical and imaging data were retrospectively collected. PET data was acquired over 12 minutes with simultaneous respiratory waveform recorded. The data were reconstructed into four image sets: gated-12 group and gated-4 group (using all counts and the first 4-minute counts, respectively) and ungated-12 group and ungated-6 group (using all counts and the first 6-minute counts, respectively) reconstructed with respiratory gating that retained counts corresponding to the half respiratory window near end-expiration. Image quality assessment and quantitative analysis of lesions were performed and compared among the four image sets, and subgroup analyses were performed according to lesion location, size, and metabolic activity. Results The effective counts of 4 sets of PET images were highest in ungated-12 group, followed by ungated-6 group and gated-12 group, and lowest in gated-4 group (P＜0.001). Regardless of the metabolic level and size of the lesions, compared with the ungated-12 group and the ungated-6 group, the lesions in the gated-12 group showed higher maximum, average, and peak standardized uptake values (SUV_max, SUV_mean, and SUV_peak), tumor liver uptake ratio, tumor blood pool uptake ratio, and smaller metabolic volume (P＜0.05); There was no statistically significant difference in the above indicators between the gate-12 group and the gate-4 group. The background noise of gate-4 group images is slightly higher than that of gate-12 group images (Liver SUV_SD: [0.17＋0.05] vs [0.14＋0.04]); Blood pool SUV_SD: (0.08 ± 0.03) vs (0.06 ± 0.03). There was a statistically significant difference in subjective scores of PET image quality among the four groups (P＜0.001). The subjective scores of image quality in the gated-12 group (4.79 ± 0.41) were not significantly different from those in the non gated-12 group (4.97 ± 0.17) and non gated-6 group (4.79 ± 0.45), but were higher than those in the gated-4 group ([4.17 ± 0.45], P＜0.001)， And the scores have good consistency (Kappa＞0.75). Conclusion In total-body PET/CT imaging for malignant tumors, 4-minute respiratory-gated acquisition can achieve comparable quantitative performance to longer respiratory gating imaging while significantly shortening acquisition time. This approach demonstrates promising potential for clinical application.

AIM: To investigate the effect and potential mechanism of liraglutide(LIR)combined with neural stem cells(NSCs)in alleviating diabetic retinopathy(DR)in rats.METHODS:A DR rat model was established using a high-fat diet combined with a single intraperitoneal injection of streptozotocin(STZ). Rats in the control group were fed a normal diet and received an intraperitoneal injection of citric acid-sodium citrate buffer. After modeling, the rats were divided into the control group, DR group, DR+LIR group, DR+BMSCs group, DR+NSCs group, DR+BMSCs+LIR group, and DR+NSCs+LIR group. According to the grouping instructions, rats were given intraperitoneal injection of LIR at 200 μg/(kg·d)and intravitreal injection of bone marrow mesenchymal stem cells(BMSCs), or NSCs, or the combined therapy accordingly for 8 wk. Fasting blood glucose(FBG)and serum insulin levels, as well as retinal oxidative stress indexes and serum inflammatory indexes, were detected in each group. Retinopathy was evaluated by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by TUNEL staining, SIRT1 expression in retinal tissues was detected by immunohistochemistry, and BDNF expression in retinal tissues was detected by immunofluorescence. The transcriptional levels of cZNF532, miR-29a-3p, SIRT1, TGF-β1, NRF2, Keap1, and BDNF in retinal tissues were detected by qRT-PCR, and the protein expression levels of SIRT1, TGF-β1, SMAD2/3, p-SMAD2/3, NRF2, Keap1, p65, and p-p65 in retinal tissues were detected by Western blot. RESULTS:Compared with the other groups of rats, the retinal morphology of rats in the DR+NSCs+LIR group was significantly improved, the levels of FBG, TNF-α, IL-1β, IL-6 and MDA were decreased(all P<0.05), the serum insulin level and the levels of SOD, CAT, and GSH-Px were increased(all P<0.05), the TUNEL-positive rate of retinal cells was reduced(all P<0.05). The expression levels of cZNF532, SIRT1, NRF2, and BDNF in retinal tissue were up-regulated(all P<0.05), whereas the expression levels of miR-29a-3p, TGF-β1, p-SMAD2/3, Keap1, and p-p65 were down-regulated(all P<0.05). CONCLUSION:LIR combined with NSCs alleviates DR by regulating the cZNF532-miR-29a-3p-SIRT1 network and its downstream TGF-β/SMAD, NF-κB, and Keap1/NRF2 signaling pathways.

ObjectiveTo establish a mouse model of hypoxic pulmonary hypertension (HPH) through intermittent hypoxia induction, and to develop a comprehensive and reliable evaluation system for the HPH model, thereby providing experimental evidence for mechanistic studies and translational applications related to this disease. MethodsTwenty-four male specific pathogen-free (SPF) BALB/c mice were randomly divided into a control group and a model group, with 12 mice per group. Mice in the model group were placed in a hypobaric oxygen chamber control system to establish the HPH model, whereas mice in the control group received no intervention. After 28 days of modeling, a comprehensive evaluation of the pathophysiological characteristics of both groups was performed using a general condition scoring scale, echocardiography, hemodynamic measurements, blood gas analysis, hematological tests, organ coefficient determination, histopathological examination, and enzyme-linked immunosorbent assay (ELISA). In addition, correlation analyses were conducted among echocardiographic parameters, the contents of endothelin‑1 (ET‑1) and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) in lung tissue, and other measured indices. ResultsWith prolonged modeling duration time, body weight, water intake, and activity level of mice in the model group were significantly decreased compared with the control group (P<0.05). Echocardiography showed that, compared with the control group, the model group exhibited increased right ventricular dimensions (P<0.01), right ventricular anterior wall thickening (P<0.01), and widened main pulmonary artery diameter (P<0.01), whereas the peak systolic velocity across the pulmonary valve, tricuspid annular plane systolic excursion, and peak systolic velocity of the tricuspid annulus were significantly decreased (P<0.001); tricuspid regurgitation was observed in some model animals. Hemodynamic results revealed that right ventricular systolic pressure was elevated in the model group compared with the control group (P<0.001). Blood gas analysis showed that pH, partial pressure of oxygen, oxygen saturation, actual bicarbonate, and total carbon dioxide were all decreased in the model group compared with the control group (P<0.01). Hematological indices demonstrated that lymphocyte counts (P<0.05) and reticulocyte counts (P<0.001) were decreased in the model group compared with the control group. Compared with the control group, the organ coefficients of heart and lung in the model group were significantly increased (P<0.05 and P<0.001). Pathological examination revealed that the right ventricular hypertrophy index was significantly increased in the model group (P<0.001), with varying degrees of damage to the right ventricle, pulmonary artery, and pulmonary vessels; both the pulmonary artery wall thickness percentage and the pulmonary wall area percentage were significantly elevated (P<0.001). ELISA results showed that the levels of ET‑1 and NT‑proBNP in lung tissues were significantly increased in the model group compared with the control group (P<0.05 and P<0.001, respectively). Correlation analysis indicated that some echocardiographic parameters were highly correlated with multiple indices in the development of HPH (P<0.05). ConclusionEchocardiography can accurately assess a series of hemodynamic changes in HPH, including right ventricular structural, functional impairment, and pulmonary hypertension. Laboratory tests not only help verify whether the model has been successfully established, but also provide deeper insights into the pathogenesis of HPH, evaluate the effects of interventions, and offer scientific evidence for clinical outcomes. Pathological examination can further confirm the alterations in pulmonary vascular remodeling and increased right heart load. This multimodal analysis provides a reliable animal model and evaluation paradigm for both basic and translational research on HPH, and is of great significance for exploring disease mechanisms and developing precision therapeutic strategies.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel characterized by high Ca²⁺ permeability, rapid activation, and rapid desensitization. It is widely expressed in the nervous system and various non-neuronal cell types. α7 nAChR is involved in regulating neuronal excitability, synaptic transmission and plasticity, cognitive function, and inflammatory responses. These properties have made α7 nAChR a potential therapeutic target for neuropsychiatric and inflammatory diseases. In recent years, advances in cryo-electron microscopy have provided structural insights into α7 nAChR gating, ligand recognition, allosteric modulation, and allosteric activation. The receptor mainly undergoes transitions among resting, open, and desensitized states. Recent structural studies have further revealed asymmetric conformational changes and multiple intermediate states during receptor activation and recovery from desensitization. Conformational rearrangements in the extracellular domain-transmembrane domain coupling region and the pore-forming M2 helices are closely associated with channel opening and desensitization. However, structural characterization of the α7 nAChR gating cycle still largely depends on pharmacological stabilization. Open-state structures have been resolved in the presence of PNU-120596 or GAT107, whereas a high-resolution structure of the open state induced by acetylcholine alone remains to be determined. These physiological roles underpin the involvement of α7 nAChR in multiple disease processes. In the hippocampus, α7 nAChR regulates local neuronal circuits, theta oscillations, synaptic transmission, and synaptic plasticity, thereby contributing to learning, memory, attention, and other cognitive processes. In macrophages, microglia, and other immune-related cells, α7 nAChR activation regulates inflammatory responses and oxidative stress. These effects involve several signaling pathways, including Janus kinase 2 (JAK2)/STAT3, phosphoinositide 3-kinase (PI3K)/AKT, and NF-κB signaling, as well as regulation of the NLRP3 inflammasome and IL-1β production. Such anti-inflammatory effects may also contribute to α7 nAChR-mediated neuroprotection. Although several compounds targeting α7 nAChR have entered clinical studies, no α7 nAChR-selective drug has been approved for clinical use. Limited clinical translation may be related to rapid receptor desensitization, inconsistent efficacy across clinical studies, insufficient or variable target engagement, patient heterogeneity, and clinical endpoint selection. TC-5619 showed promising effects on cognitive impairment and negative symptoms in an early exploratory study of schizophrenia, but these effects were not confirmed in a subsequent, larger phase II trial. Encenicline (EVP-6124) also showed cognitive improvement in early studies, whereas two global phase III trials in schizophrenia failed to meet their co-primary cognitive and functional endpoints. Pharmacological strategies targeting α7 nAChR have expanded from orthosteric agonists to positive allosteric modulators (PAMs) and allosteric agonist-positive allosteric modulators (ago-PAMs). Orthosteric agonists directly activate the receptor by binding to the orthosteric site, but their effects are limited by rapid receptor desensitization. Type I PAMs mainly enhance agonist-evoked responses with relatively small effects on desensitization, whereas type II PAMs markedly potentiate receptor responses and reduce or delay desensitization. Ago-PAMs such as GAT107 can directly activate α7 nAChR through an allosteric mechanism while also potentiating responses to orthosteric agonists. Together, these findings have broadened the pharmacological approaches to α7 nAChR regulation. In summary, future drug development should focus on precise regulation of α7 nAChR according to receptor structure and disease mechanisms, rather than simply enhancing receptor activation. Further studies are needed to clarify how candidate ligands affect receptor gating, conformational transitions, recovery from desensitization, and downstream signaling. Pharmacological differences between neuronal and non-neuronal α7 nAChRs, between homomeric α7 and heteromeric α7β2 receptors, and between α7 nAChR and other nAChR subtypes also require further investigation. Integrating structure prediction, artificial intelligence-assisted virtual screening, molecular docking, molecular dynamics simulations, and electrophysiological validation may facilitate the discovery and optimization of new α7 nAChR modulators.

Objective To construct an injectable hydrogel(IH)entrapment system of bone marrow mesenchymal stem cells(BM-MSCs)and to explore its effect of promoting articular cartilage repair and underlying mechanism.Methods The primary BM-MSCs of mice were cultured by whole bone marrow adherent method.The differentiation potential was identified by alizarin red(ARS),oil red O(ORO)and Alcian blue(AB)staining,and the expres-sion of CD44,CD90,CD105,CD34 and CD45 on the surface was detected by flow cytometry.BM-MSCs loaded with IH(BM-MSC-IH)was prepared,and the rheological properties of BM-MSC-IH were tested by rheological test.The model of full-thickness injury of knee cartilage in mice was established,and the mice were randomly divided into normal saline group,BM-MSC group and BM-MSC-IH group with 8 in each.The mice were injected with BM-MSC-IH 0.2 mL,cell suspension 0.2 mL and 0.9％NaCl solidion,independently.After 6 and 12 weeks of in-jection,the repair of knee cartilage in mice was observed by safranin-fast green staining,and the expression of typeⅡ collagen in knee joint was examined by immunohistochemical staining microscopy.Results The primary cultured cells showed positive expression of CD44,CD90 and CD105,but negative expression of CD34 and CD45,and had the potential of osteogenic,adipogenic and chondrogenic differentiation.The constructed BM-MSC-IH sys-tem was solid colloid,and the rheological properties were consistent with the basic characteristics of hydrogel.BM-MSC-IH effectively promoted the regeneration of mouse knee cartilage and increase the local expression of typeⅡ collagen.Conclusions Bone marrow-mesenchymal stem cells embedded with injectable hydrogel effectively pro-mote the repair of injured cartilage and the underlying mechanism is potentially promoting the differentiation of chondrocytes and the expression of type Ⅱ collagen.Its effect is better than application of BM-MSCs alone.

Objective To observe the morphology of the superficial,middle,and deep layers of the masseter muscle and related bony structures in the lateral facial region of adults through gross anatomy,and to probe into the effects of these muscle layers on the bony structures of the lateral facial region.Methods The bilateral masseter muscles of 12 adult cadavers were exposed,and the superficial,middle,and deep layers were separated and measured for muscle length,tendon length,and muscle belly length.After the masseter muscles were stripped,the total thickness was measured,and the mandible and zygomatic arch were exposed to measure the angle of the mandibular angle,thickness of the zygomatic arch,and width of the zygomatic arch.Observations were made of the masseter tuberosities,and statistical analysis was conducted on their interrelations.Results The zygomatic arch thickness was positively correlated with the length of superficial,middle and deep masseter muscles and the length of superficial and middle masseter belly(r superficial masseter length=0.624,r middle masseter length=0.787,r deep masseter length=0.423,r superficial masseter belly length=0.493,r middle masseter belly length=0.548).The width of the zygomatic arch was positively correlated with the lengths of the superficial and middle muscle layers and the middle muscle belly length(r superficial masseter length=0.527,r middle masseter length=0.521,r middle masseterbelly length=0.437).The angle of the mandibular angle was only negatively correlated with the middle muscle belly length(r=-0.422).The tuberosities of the superficial and middle masseter muscles were not affected by the corresponding muscle layers;However,the tuberosity of the deep masseter was negatively correlated with the length of the deep muscle and the length of the deep tendon(r deep masseter length=-0.543,r deep masseter tendon length=-0.443).Conclusion In the masseter muscle layers of Chinese individuals,the superficial and middle layers have the most significant impact on the bony structures structures of the lateral facial region.These findings are of guiding significance for the remodeling of structures in the lateral facial region.