OBJECTIVE To introduce the characteristics and practice of billable pharmacy service programs in the United States， aiming to provide reference for the development of clinical pharmacy service and the establishment of corresponding billing criteria in China. METHODS By searching the official websites of American Pharmacists Association， American Society of Health- System Pharmacists， Centers for Medicare & Medicaid Services and Centers for Disease Control and Prevention， and the PubMed database， the contents of American billable pharmacy service programs， corresponding service billing criteria， the approaches to being paid as pharmacists and the clinical practice evidence were summarized. RESULTS Current major billable pharmacy service programs implemented in the United States included medication therapy management， outpatient pharmacy service， transition of care management， chronic disease management， annual wellness visits， as well as diabetes self-management training/education. Except for diabetes self-management training/education， which lacked robust data on practice outcomes， all other programs mentioned above were demonstrated to have positive impact on patient outcomes， reducing health care cost and/or generating revenues. The most common approaches for pharmacists to obtain reimbursement were “incident to” billing and using procedure codes. CONCLUSIONS Billable pharmacy practice programs in the United States are achieving progress in service specialization and billing standardization. China can learn from successful cases in the United States while considering its own national context， with the ultimate goal of improving the overall health outcomes of patients， so that pharmacy services can become an important part of the medical service system.

Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

Myocardial infarction （MI） refers to an acute clinical syndrome of myocardial necrosis due to persistent ischemia and hypoxia， resulting from the sharp reduction or interruption of coronary blood flow. Nuclear factor κB （NF-κB） is the key factor in inducing inflammatory response， and it is involved in the production of pro-inflammatory factors and myocardial cell apoptosis. This article systematically describes the molecular regulation mechanism of the NF-κB signaling pathway in MI， and reviews the related research on the prevention and treatment of MI through the regulation of this signaling pathway by active ingredients and compound formulas from traditional Chinese medicine （TCM）. It has been found that active ingredients from TCM， such as ginsenoside Rg3， baicalein， curcumin， tanshinone ⅡA， gambogic acid， as well as compound formulas， including Qili qiangxin capsules， Yiqi huoxue decoction， Lingbao huxin dan， Danhong injection， Baoyuan decoction combined with Taohong siwu decoction， can improve myocardial fibrosis， alleviate inflammatory responses， and inhibit cardiomyocyte apoptosis by suppressing the NF-κB signaling pathway. Thereby， they achieve the goal of preventing and treating MI.

Aim To establish an efficient and stable isolation method of primary mouse brain vascular smooth muscle cells and endothelial cells,and provide experimental materials for the investigation of pathogenesis and treatment of brain vascular diseases.Methods Brain vascular smooth muscle cells were isolated by dextran gradient centrifugation with enzymatic digestion,and endothelial cells were isolated by immunomagnetic beads sorting.Morphology and growth characteristics of two types of cells were observed with an inverted phase contrast microscope,their purity were identified by immunofluorescence,and their proliferation characteristics were observed by CCK-8 assay.At the level of cellular func-tion,angiogenic capacity of endothelial cell was assessed by angiogenesis assay and smooth muscle cell responsiveness to platelet-derived growth factor(PDGF)was assessed by migration assay.Results The two types of cells isolated using this method grew vigorously and were in good condition.Smooth muscle cells exhibited typical"peak valley"growth,and immunofluorescence results showed cytoplasmic specific smooth muscle α-SMA and SM22α expression was positive.En-dothelial cells exhibited typical"cobblestone like"growth,with positive expression of platelet endothelial cell adhesion molecule CD31 and atresia zone protein 1.Conclusion This study established a reliable and efficient method for sim-ultaneously isolating two types of cerebrovascular cells,the isolated cells have high purity,good activity,and stable charac-teristics after passage,which were sufficient to meet the needs of subsequent experiments.

Objective:To explore the influence of perceived stress on bedtime procrastination in college students,as well as the mediating role of daily ego-depletion and the moderating effect of guilt.Methods:The Per-ceived Stress Scale(PSS-4),State Self-Control Scale(SSCCS)and Bedtime Procrastination Scale(BPS)were used to track the daily perceived stress,ego-depletion and sleep procrastination of 34 college students for 14 days.The 1-1-1 and 2-1-1 multi-layer linear models were constructed by HLM to test the mediating and mod-erating effects.Results:Daily ego-depletion scores played a mediating role in the influence of daily perceived stress scores on daily bedtime procrastination scores(γ20=0.49,P＜0.001),guilt scores moderated the effect of daily ego-depletion scores on daily bedtime procrastination scores(γ11=0.03,P＜0.05).Conclusion:Daily perceived stress could not only directly predict bedtime procrastination on the night in college students,but also indirectly af-fect daily bedtime procrastination through daily ego-depletion.When ego-depletion is high,guilt can reduce college students'bedtime procrastination.

Objective To propose a regression tree model for the estimation of blood pressure using the minimalist characteristics of photoplethysmography(PPG)signals.Methods Fifteen characteristic parameters were extracted from the PPG signals,and the 4 parameters with the highest correlations with blood pressure were screened using the Spearman correlation coefficient to construct a regression tree model for blood pressure estimation using the minimalist characteristics.Results The estimation errors of systolic and diastolic blood pressures in the constructed model were(-0.02±3.63)mmHg and(-0.04±2.10)mmHg,respectively.Conclusion The proposed regression tree model has a simple structure and high accuracy,which is of great significance for using a single-channel PPG signal for blood pressure estimation in wearable devices.

Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Wnt signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer bibliometric software,the literature on the regulation of Wnt signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results As of April 2023,607 and 257 related literatures were published in Chinese and English respectively.Since 2008,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;guangzhou University of Traditional Chinese Medicine and Hunan University of Traditional Chinese Medicine were the institutions with the most publications in the Chinese database,and Shanghai University of Traditional Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Wnt signaling pathway are focused on osteoporosis,osteoarthritis and renal fibrosis.Diseases such as gastric cancer and breast cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.The mechanism of traditional Chinese medicine regulating the interaction between Wnt and NF-kappaB signaling pathway to prevent and treat diseases has great research potential.Conclusion In recent years,the prevention and treatment of diseases by traditional Chinese medicine targeting Wnt signaling pathway has developed rapidly.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective To analyze the relationship between serum micro RNA(miR)139-5p,histone deacetylase 4(HDAC4)and glial fibrillary acidic protein(GFAP)and the severity of brain injury in neonatal hypoxic-ischemic encephalopathy(HIE).Methods From January 2017 to March 2022,72 HIE neonates born in Guangyuan Central Hospital were collected as research objects(study group),while 75 healthy full-term newborns were the control group.The expression levels of miR-139-5p and HDAC4 in serum were detected by real-time fluorescence quantitative PCR.ELISA was applied to detect serum GFAP level.Binary logistic regression was applied to analyze the factors affecting the occurrence of severe brain injury in children with HIE.Results Compared with the control group,the serum GFAP(1.30±0.37ng/L vs 0.50±0.15 ng/L)and HDAC4 relative expression level(2.05±0.39 vs 1.02±0.21)in the study group were increased,the relative expression level of miR-139-5p(0.63±0.14 vs 1.01±0.22)and the NBNA score(33.20±1.43 score vs 39.85±2.23 score)was decreased,the differences were statistically significant(t=17.304,20.046,12.436,21.424,all P＜0.05).Compared with the mild to moderate group,the serum GFAP level(1.61±0.47ng/L vs 1.16±0.33ng/L),HDAC4 relative expression level(2.43±0.37 vs 1.87±0.40),miR-139-5p(0.38±0.10 vs 0.74±0.16)and NBNA score(30.52±1.54 score vs 34.46±1.38 score)relative expression level in the severe group were increased,and the differences were statistically significant(t=4.690,5.669,9.900,10.884,all P＜0.05).Logistic regression analysis showed that low expression of miR-139-5p,high expression of HDAC4,low NBNA score and low Apgar score within 1 min after birth were risk factors for severe brain injury in HIE children(Wald χ2=5.772～6.969,OR=1.519～1.709,all P＜0.05).Pearson analysis showed that the expression level of serum miR-139-5p was negatively correlated with GFAP,HDAC4(r=-0.416,-0.579,all P＜0.05),while the expression level of serum HDAC4 was positively correlated with GFAP(r= 0.437,P＜0.05).Spearman analysis showed that the expression level of serum miR-139-5p was positively correlated with NBNA score,Apgar score within 1 min after birth,and Apgar score within 5 min after birth(r= 0.398,0.367,0.348,all P＜0.05).Serum HDAC4 expression level was negatively correlated with NBNA score,Apgar score within 1 min after birth,and Apgar score within 5 min after birth(r=-0.364,-0.345,-0.332,all P＜0.05).Conclusion The expression of miR-139-5p in the serum of children with HIE was decreased,and the expression of HDAC4 was increased,miR-139-5p and HDAC4 were associated with the severity of brain injury in children with HIE.

Objective:To detect the expression levels of various immune cells in peripheral blood,and to ex-plore their relationship with unexplained recurrent spontaneous abortion(URSA)and its clinical significance in di-agnosis and treatment.Methods:A total of 351 patients with URSA who visited Hebei Reproductive Health Hospi-tal between January 2020 and September 2022 were enrolled as the URSA group,while a control group compri-sing 30 healthy women who had experienced uncomplicated term delivery once and had no history of adverse pregnancy outcomes during the same period was selected.The levels of various immune cell subsets in peripheral blood during the luteal phase were measured and compared between the two groups.Receiver operating charac-teristic(ROC)curve analysis was performed to determine the optimal cutoff values of immune cell levels that could assist in URSA diagnosis and treatment,while logistic regression analysis was conducted to identify factors influ-encing URSA occurrence.Results:The number and percentage of CD3+CD8+cells in the peripheral blood of the URSA group were significantly lower compared to those in the control group(P＜0.05).Conversely,the per-centage of NK cells was significantly higher in the URSA group than in the control group(P＜0.05).Logistic re-gression analysis revealed that the increase in CD3+CD8+cell count in peripheral blood during the luteal phase was a protective factor of URSA(OR＜1,P＜0.05).ROC curve analysis determined optimal cutoff values for im-mune cell levels to assist in the diagnosing and treating URSA:702.82 cells/μl for CD3+CD8+cell count,28.39％for CD3+CD8+cell percentage,and 12.33％for NK cell percentage.After using the optimal cutoff value to convert continuous variables into binary variables,Logistic regression analysis showed that a CD3+CD8+cell count＜702.82 cells/μl and an NK cell percentage＞12.33％were independent risk factors for URSA(OR＞1,P＜0.05).Conclusions:The decrease of CD3+CD8+cells in peripheral blood during midluteal phase is closely related to the occurrence of URSA.The number of CD3+CD8+cells(702.82 cells/μl)and the percentage of NK cells(12.33％)can be used as reference values for the diagnosis and treatment of URSA.