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 investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

The spine is the most common site of skeletal metastasis in lung cancer, which frequently leads to severe complications such as pathological fracture and neurological compromise and is associated with poor prognosis. The development and progression of spinal metastasis from lung cancer are linked to the unique local microenvironment and tumor microenvironment (TME) of the vertebral column. During metastatic evolution, the dense vascular network of the spine and a plethora of signaling molecules, together with the complex cellular constituents and their intricate interactions within the TME, all cooperate to facilitate the tumor invasion and colonization of the vertebral compartment. Mechanistic studies delineating the role of the TME in spinal metastasis from lung cancer have markedly expanded, fostering the emergence of innovative therapeutic strategies—including nanomedicines, sono-photodynamic therapy, gene therapy, and combination regimens. These strategies demonstrate remarkably potential for clinical translation and offer new directions for the precision management of spinal metastasis from lung cancer.

Guided by the theories of yin-yang and collateral disease， this paper identifies the dysregulation of yang qi ascent and descent as the core pathomechanism of hypertension. Based on clinical experience， a treatment approach centered on the method of raising yang and promoting descent was proposed. Clinically， three major syndrome types were identified. Firstly， deficiency of zong qi （ancestral qi） with blood stasis， obstruction of phlegm-turbidity and blood stasis， and hyperactivity of liver yang. Corresponding empirical formulation， Yizong Huoxue Decoction （益宗活血汤） was applied to tonify zong qi， invigorate blood， and raise yang. Secondly， Lizong Huoxue Decoction （理宗活血汤） was used to resolve phlegm， promote yang qi circulation， and regulate qi and blood. Thirdly， Qinggan Tongluo Decoction （清肝通络饮） was used to clear the liver， dredge collaterals， and subdue hyperactive yang. For special types such as non-dipper hypertension， time-specific syndrome differentiation and treatment can be applied based on a thorough understanding of the underlying pathomechanism， aiming to provide new insights into clinical diagnosis and treatment of hypertension.

Chronic heart failure （CHF） is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body， or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health， necessitating attention and active intervention. At present， western medicine treatment of CHF is mainly based on diuretics， intravenous vasodilators， intravenous positive inotropic drugs， etc.， which， however， have problems such as long medication cycles， serious side effects， and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway， multi-component， and multi-target manner， showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi， activating blood， and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients， which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients， which helps to improve the accuracy of efficacy evaluation. However， there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition， the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment， Buyang Huanwutang can be used alone， or modified， or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance， protecting the mitochondrial structure and function， and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.

Objective To generate a dense granule protein 3 (GRA3) gene-deficient mutant of the Toxoplasma gondii ME49 strain and to test the virulence of the mutant. Methods Gene-deficient parasites were generated with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system. Guide RNA (gRNA) was designed using the E-CRISPR software, and mutated on the pSAG1::Cas9-U6::sgUPRT plasmid using the Q5 site-directed mutagenesis kit to generate the pSAG1::Cas9-U6::sgGRA3 plasmid. A GRA3 donor plasmid containing GRA3 gene upstream sequences, pyrimethamine resistant gene dihydrofolate reductase-thymidylate synthase (DHFR-TS) and GRA3 gene downstream sequence was generated, and GRA3 donor DNA was amplified using PCR assay. The pSAG1::Cas9-U6::sgGRA3 plasmid and GRA3 donor DNA were electroporated into tachyzoites of the wild-type T. gondii ME49 strain. Then, parasite suspensions were inoculated into human foreskin fibroblast (HFF) cells and screened with pyrimethamine to yield pyrimethamine-resistant parasites for monoclonal screening. The GRA3 gene deficient monoclonal strain (ME49Δgra3) of T. gondii was identified using PCR and Western blotting assays, and the expression of GRA3 protein was determined in the T. gondii ME49Δgra3 strain using Western blotting. Subsequently, 1 000 freshly lysed tachyzoites of T. gondii ME49 and ME49Δgra3 strains were transferred to 12-well plates seeded with HFF cells, and incubated at 37 °C containing 5% CO₂ for 7 days, and the number of plaques was counted by staining with crystal violet solutions. HFF cells infected with tachyzoites of T. gondii ME49 and ME49Δgra3 strains were stained using Giemsa solutions, and the numbers of cells containing 1, 2, 4, and > 4 T. gondii parasitophorous vacuoles were counted. In addition, the survival rates of C57BL/6 mice infected with T. gondii ME49 and ME49Δgra3 strains were compared 35 days post-infection. Results PCR assay revealed successful amplification of both the upstream and downstream homologous arm bands of the DHFR-TS gene in the T. gondii ME49Δgra3 strain, and no corresponding bands were amplified in the ME49 strain. The GRA3 band was amplified in the ME49 strain, and the DHFR-TS band, rather than GRA3 band, was amplified in the ME49Δgra3 strain. Western blotting determined absence of GRA3 protein expression in the ME49Δgra3 strain. Crystal violet staining showed that the T. gondii ME49 strain produced more plaques than the ME49Δgra3 strain [(352.67 ± 26.39) plaques vs. (235.00 ± 26.29) plaques; t = 5.472, P < 0.01], and Giemsa staining revealed that the proportion of T. gondii parasitophorous vacuoles containing at least four T. gondii tachyzoites was higher in HFF cells infected with the ME49 strain than in those infected with the T. gondii ME49Δgra3 strain [(75.67 ± 2.52)% vs. (59.67 ± 2.31)%; t = 8.113, P < 0.01], and the proportion of T. gondii parasitophorous vacuoles containing at least 1 or 2 T. gondii tachyzoites was higher in HFF cells infected with the T. gondii ME49 strain than in those infected with the T. gondii ME49Δgra3 strain [(24.33 ± 2.52)% vs. (40.33 ± 2.31)%; t = −8.113, P < 0.01]. In addition, mice infected with the T. gondii ME49 and ME49Δgra3 strains started to die 8 and 9 days post-infection, and the 35-day mortality rates of mice infected with T. gondii ME49 and ME49Δgra3 strains were 10.00% and 70.00% post-infection (χ² = 6.762, P < 0.01). Conclusions The T. gondii ME49Δgra3 strain has been successfully generated, and GRA3 protein may increase the virulence of the T. gondii ME49 strain.

Malaria, a parasitic disease caused by infection with the species of Plasmodium and transmitted by Anopheles mosquito bites, is one of the major public health challenges that seriously threaten human health. Malaria parasites present diverse immune escape strategies to escape from the recognition and clearance of the host immune system, which poses a great challenge to the malaria control programme. This review presents the advances in the mechanisms underlying the immune escape of Plasmodium, including antigenic variation, epigenetic regulation, antagonism against IgM antibody, activation of the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling, suppression of splenic immune functions, and molecular camouflage, so as to provide insights into development of malaria vaccines and antimalarial agents and formulation of the malaria control strategy.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.