OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy， and ensure the safety of drug use in patients. METHODS SWOT （strength， weakness， opportunity， threat） analysis method was used to analyze the internal strengths and weaknesses， as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital， and propose improvement strategies. RESULTS & CONCLUSIONS A refined， full-process， closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established， which is traceable in origin， trackable in destination， and accountable in responsibility. After the application of this system， the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020， the inventory volume decreased by 29.50% compared to the first quarter of 2020， the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020； the average workload per post in the same period of 2023 increased by 49.09% compared to 2019， the dispensing accuracy rate reached 100%， and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.

AIM: To investigate the risk factors associated with the recurrence of macular edema secondary to branch retinal vein occlusion(BRVO-ME)after anti-vascular endothelial growth factor(anti-VEGF)therapy.METHODS:A total of 32 patients(32 eyes)with BRVO-ME who were treated at the ophthalmology department of the Affiliated Hospital of Shandong Second Medical University from February 2021 to June 2022 were selected. They were treated with a 3+pro re nata (PRN)anti-VEGF regimen and followed up for 6 mo. Following 3 consecutive anti-VEGF injections, patients were categorized into a non-recurrence group and a recurrence group based on central macular thickness(CMT)measured by optical coherence tomography(OCT)at 6 mo post-treatment. Aqueous humor levels of various cytokines levels were quantified using suspension assay method. Demographic characteristics, CMT, and cytokine levels were compared between the two groups, and their correlations with the recurrence of BRVO-ME after anti-VEGF treatment were analyzed.RESULTS:At 6 months post-treatment, ME resolved in 19 eyes(no recurrence group), while 13 eyes showed persistent or recurrent ME(recurrence group). Compared to baseline, the CMT significantly improved in both groups at 1 d, 1, and 6 mo post-treatment(all P<0.05). However, the recurrence group exhibited significantly higher baseline, 1 d and 6 mo post-treatment CMT values than the non-recurrence group(all P<0.05). The aqueous humor levels of VEGF and monocyte chemoattractant protein-1(MCP-1)at baseline were significantly higher in the recurrence group than the non-recurrence group(all P<0.05). Spearman correlation analysis revealed positive associations between baseline CMT and interlukin IL-1β, IL-5, IL-12, MCP-1 and IP-10 levels(all P<0.05). Multivariable Logistic regression analysis identified baseline CMT and MCP-1 levels as independent risk factors for BRVO-ME recurrence(OR>1, P<0.05).CONCLUSION: Elevated baseline CMT and aqueous humor MCP-1 levels were identified as independent risk factors for BRVO-ME recurrence after anti-VEGF therapy. Patients exhibiting higher baseline CMT and MCP-1 levels demonstrated significantly increased susceptibility to recurrence.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Astragalus membranaceus possesses the function of enhancing immunity, protecting the liver, diuretic, anti-aging, anti-stress, anti-hypertensive, and more extensive antibacterial effects. Polysaccharides, one kind of the major active ingredients of A. membranaceus, are considered to be responsible for their versatile use. Now, a systematic summary of research progress and prospects of polysaccharides from A. membranaceus polysaccharides (AMPs) is necessary to facilitate their further study and application. In this review, the optimal extraction methods, structural features, biological activities, and applications of AMPs were emphasized. The structure-activity relationships are also analyzed and elucidated. Solvent, ultrasonic, microwave, enzyme-assisted, ultra-high pressure, and combined methods have been used to extract AMPs. Among them, solvent extraction is the most commonly used method because it is simple and easy to operate, but the efficiency needs to be improved further. The ultra-high pressure method is the most efficient but has a low economic return. AMPs exhibited various bioactivities, including immunomodulation, antitumor, and antidiabete. The structure-activity relationships revealed that different structure configurations, chain conformations, and physical properties would have different bioactivities. However, the new method for purification of certain polysaccharides, detailed structure-activity relationships (SAR), mechanisms of bioactivities, and quality control of AMPs need to be extensively investigated.

Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO₂) (200 mg·mL^-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO₂ group, (2) SiO₂+negative control siRNA (siRNA-NC) group and SiO₂+Smurf2 gene silencing (si-Smurf2) group, (3) SiO₂+solvent (DMSO) group and SiO₂+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO₂+miR-NC group and SiO₂+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO₂-induced MLE-12 cells, compared to the control group, the SiO₂-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO₂, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO₂ group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

Objective To investigate the effects of menaquinone-4(MK4)on the activation and function of CD8+T cells.Methods An in vitro culture system for primary mouse CD8+T cells was established by isolating these cells from the spleen using CD8a T cell isolation kit.The isolated CD8+T cells were then incubated and activated in a 96-well plate coated with anti-CD3/CD28 antibodies.The impact of MK4 on the activation and cytokine secretion of CD8+T cells was explored by quantifying the expression levels of CD8+T cell activation receptors and cytokines using flow cytometry.Additionally,the concentrations of these cytokines in the culture supernatant were measured by enzyme-linked immunosorbent assay(ELISA).The influence of MK4 on the anti-tumor function of CD8+T cells was evaluated by co-culturing colorectal cancer MC38 cells of mice with CD8+T cells at different ratios,and the effect of MK4 was assessed by detecting tumor cell apoptosis.Results High-purity primary CD8+T cells of mice(97.5％)were isolated using the magnetic bead,which could be activated by pre-coated CD3/CD28 antibodies and showed proliferation.Compared with the control group,the MK4-treated group exhibited increased expressions of CD25,CD69 and CD44 on CD8+T cells,as well as higher production and secretion levels of interleukin-2(IL-2),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)and granzyme B.In addition,CD8+T cells in the MK4-treated group induced a higher percentage of tumor cell apoptosis(36.7％)compared with the control group(29.1％).Conclusion MK4 can enhance the activation of CD8+T cells and promote anti-tumor functions.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

Objective:To explore influencing factors affecting the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy based on hematologic indexes, thus to construct and evaluate a nomogram prediction model.Methods:The clinical data of 80 patients with advanced NSCLC treated with programmed death-1 inhibitor monotherapy or combination regimen from January 2018 to June 2020 at the Affiliated Hospital of North China University of Science and Technology and Tangshan People's Hospital were retrospectively analyzed. Hematologic indexes at the baseline, the optimal remission and the progressive disease (PD) were collected separately, and independent influencing factors for patient prognosis were analyzed using Cox proportional hazards regression model. A nomogram prediction model was constructed based on the results of the multifactorial analysis, and the predictive performance of the model was evaluated by receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curves.Results:As of the follow-up cut-off date, of the 80 patients, 63 had PD, with a median overall survival (OS) of 16.9 months. Univariate analysis showed that, age ( HR=2.09, 95% CI: 1.17-3.74, P=0.013) , number of treatment lines ( HR=2.23, 95% CI: 1.21-4.12, P=0.010) , lymphocyte to monocyte ratio (LMR) at the baseline ( HR=0.75, 95% CI: 0.57-0.97, P=0.028) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) and lactate dehydrogenase (LDH) ( HR=1.01, 95% CI: 1.00-1.01, P=0.006) at the optimal remission, haemoglobin ( HR=0.97, 95% CI: 0.96-0.99, P<0.001) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) , C-reactive protein ( HR=1.01, 95% CI: 1.00-1.01, P=0.011) , albumin (ALB) ( HR=0.91, 95% CI: 0.87-0.96, P=0.001) , neutrophil to lymphocyte ratio (NLR) ( HR=1.16, 95% CI: 1.05-1.27, P=0.002) and LMR ( HR=0.62, 95% CI: 0.42-0.90, P=0.012) at the PD were all influencing factors for the prognosis of advanced NSCLC patients receiving immunotherapy. Least absolute shrinkage and selection operator regression were used to screen the variables for P<0.10 in the univariate analysis, and nine possible influencing factors were obtained, which were age, fibrinogen and LDH at the optimal remission, haemoglobin, D-dimer, C-reactive protein, LDH, ALB and LMR at the PD. Multivariate analysis of the above variables showed that, age ( HR=0.91, 95% CI: 0.86-0.97, P=0.004) , LDH ( HR=1.01, 95% CI: 1.00-1.01, P=0.013) and ALB ( HR=0.82, 95% CI: 0.67-0.99, P=0.041) at the PD were independent influencing factors for the prognosis of patients with advanced NSCLC who received immunotherapy. The area under curve of the nomogram predicting model based on the above indexes, 1- and 2-year OS rates of patients were 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.66-0.88) , respectively, and C-index was 0.71 (95% CI: 0.64-0.78) , the calibration curves showed good consistency between predicted and actual probability of occurrence. Patients in the low-risk group ( n=40) had a median OS of 29.9 months (95% CI: 22.5 months-NA) , which was significantly better than that of the high-risk group ( n=40) [13.4 months (95% CI: 11.4-23.5 months) , χ2=11.30, P<0.001]. Conclusion:Age, LDH and ALB at the PD are independent influencing factors affecting the prognosis of patients with advanced NSCLC receiving immunotherapy, and the nomogram model constructed based on the above indexes has good differentiation and calibration for predicting 1- and 2-year OS rates in advanced NSCLC patients receiving immunotherapy.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.