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 investigate the immunotoxicity and potential mechanism of Carthamus tinctorius extract on RBL-2H3 cells via direct induction and induction by sensitized serum prepared with an overdose of the extract. METHODS For direct induction by C. tinctorius extract， RBL-2H3 cells were divided into normal control group （no treatment） and C. tinctorius extract group （10 mg/mL）. For induction by sensitized serum prepared with an overdose of C. tinctorius extract， rats were divided into normal control group （no treatment）， adjuvant-treated group （1 mL adjuvant）， C. tinctorius extract-induced sensitization group （2.04 g/mL）， and ovalbumin （OVA）-induced sensitization group （50 mg/mL）. Sensitization was performed once every other day for a total of 3 times. Morphological changes of RBL-2H3 cells were observed， the degranulated rate of cells was counted， and histamine content was determined； the release rate of β -hexosaminidase （ β -Hex） was calculated， the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） and intracellular Ca²⁺ concentration were detected. RESULTS Under direct induction by C. tinctorius extract， compared with the normal control group， the volume of cells in the C. tinctorius extract group was significantly reduced and cell density decreased； the degranulation rate of cells， histamine content， β -Hex release rate， IL-6 and TNF-α levels， as well as intracellular Ca²⁺ concentration were all significantly increased （ P ＜0.01）. Under i nduction by sensitized serum prepared with an overdose of C. tinctorius extract， compared with the adjuvant-treated group， the above indicators in the C. tinctorius extract-induced sensitization group and the OVA-induced sensitization group showed consistent changes with those in the C. tinctorius extract group under direct induction， all being significantly elevated （ P ＜0.01）. CONCLUSIONS C. tinctorius extract may affect degranulation of RBL-2H3 cells and promote Ca²⁺ influx accompanied by the release of pro-inflammatory cytokines through two approaches： direct induction and induction by sensitized serum prepared under overdose administration. Its mechanism may be related to the activation of the calcium signaling pathway and the regulation of inflammatory pathways under the synergistic effect of multiple components.

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.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective To report the individualized rehabilitation protocol administered to a patient suffering from corpus callosum injury subsequent to cerebral infarction,manifesting clinically as alien hand syndrome,attention deficits,spatial neglect and gait apraxia;and to emphasize the application of functional near infrared spectroscopy(fNIRS)in the assessment of cerebral activation.Methods A 54-year-old male with corpus callosum damage following cerebral infarction was assessed by a comprehen-sive array of neuropsychological assessments,such as Mini-Mental State Examination,Montreal Cognitive As-sessment,Loewenstein Occupational Therapy Cognitive Assessment and Wisconsin Card Sorting Test,etc.Based on these assessments,a personalized rehabilitation program was devised,incorporating physical therapy,occupa-tional therapy,task-oriented training,mirror therapy,computer-assisted cognitive training,as well as Schulte's square attention training,bilateral limb coordination training and transcranial magnetic stimulation(TMS).fNIRS was used to evaluate changes in brain activation before and after rehabilitation.Results After more than a month of comprehensive rehabilitation,the patient experienced significant improvements in Alien hand syndrome,attention deficit and spatial neglect.Gait was normalized,and enhancements were ob-served in motor function,cognition and activity of daily living.fNIRS analysis revealed favorable alterations in cerebral activation patterns.Conclusion For the intricate symptoms associated with corpus callosum injury,a multidisciplinary rehabilitation ap-proach,particularly the incorporation of Schulte's square attention training,bilateral coordination exercises and TMS,alongside fNIRS for monitoring cerebral activation,showed significant rehabilitation effects.

Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Objective:To analyze the physical activity level of patients treated with a percutaneous coronary intervention (PCI) for coronary artery disease in the early out-of-hospital recovery phase, and the factors influencing it.Methods:Patients who had been discharged within the previous 6 months after their first PCI treatment were surveyed using a general information questionnaire, the long form of the International Physical Activity Questionnaire (IPAQ), the Chinese version of the Tilburg Frailty Scale, the Social Support Rating Scale, and for their ability in the activities of daily living. Epidemiological descriptive methods were used to analyze the reported physical activity levels, and multifactoral logistic regression was applied to explore the influencing factors. The receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of the risk factors.Results:A total of 394 former patients were surveyed, including 117 (30%) reporting a low level of physical activity, 202 (51%) describing a moderate level and 75 (19%) claiming a high level. The univariate analysis revealed significant differences in physical activity levels among those of different ages, with different chronic co-morbidities, and with different frailty and self-care ability. Multifactoral logistic regression analysis showed that advanced age, chronic co-morbidities, frailty and little self-care ability are significant predictors of a low level of physical activity. The area under the ROC curve for predicting the physical activity level by combining those four factors was 0.89 (95% CI 0.84-0.94), with a sensitivity of 0.89 and a specificity of 0.80. Conclusions:The physical activity level of patients treated with PCI for coronary disease is moderately low early after their release from the hospital. Targeted intervention to increase it is called for.