OBJECTIVE To provide references for ensuring the safety of prescription preparation， dispensing， and use of parenteral nutrition solution， as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services （PIVAS）. METHODS Under the guidance of PIVAS pharmacists， the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened， and detailed quality control and inspection rules were formulated. Additionally， Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions， infusion operations， and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition， the rate of irrational medical orders， the compliance rate of vascular access selection and infusion rate standardization， the rate of dispensing error， as well as the abnormalities occurring during clinical use， before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition， enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%， respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system， improving labeling information， and strengthening quality control inspections during both preparation and administration processes， PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Computational approaches for predicting drug-target interactions (DTIs) are pivotal in advancing drug discovery. Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information. To comprehensively consider network information, we propose DHGT-DTI, a novel deep learning-based approach for DTI prediction. Specifically, we capture the local and global structural information of the network from both neighborhood and meta-path perspectives. In the neighborhood perspective, we employ a heterogeneous graph neural network (HGNN), which extends Graph Sample and Aggregate (GraphSAGE) to handle diverse node and edge types, effectively learning local network structures. In the meta-path perspective, we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths, such as "drug-disease-drug", and use an attention mechanism to fuse information across multiple meta-paths. The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method. Furthermore, DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy. Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods. Additionally, case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.

OBJECTIVE To investigate the efficacy and safety of hetrombopag combined with low-dose prednison in the treatment of patients with refractory/recurrent primary immune thrombocytopenia(ITP). METHODS A total of 40 patients with ITP who failed to respond to previous treatment or relapsed in the Department of Hematology of Gansu Provincial People’s Hospital From July 2021 to August 2022 were selected. Used randomized controlled trial research methods, according to the treatment plan, they were divided into observation group and control group, with 20 cases in each group. The control group was treated with low-dose prednison alone. The observation group was combined with hetrombopag treatment on this basis. The efficacy and adverse reactions were compared between the two groups. RESULTS Treatment 6 weeks, patients who's proportion of platelet counts(PLT) reached≥50×109·L−1 and ≥30×109·L−1 in observation group were higher than control group with statistically significant differences in both groups[90%(18/20) vs 50%(10/20), P＝0.006; 90%(18/20) vs 65%(13/20), P＝0.130]; The study also indicated a statistically significant difference in favour of observation group compared with control group in the odds of achieving the outcome of a PLT≥50×109·L−1at least once during 6-week treatment[90%(18/20) vs 55%(11/20), P＝0.147], was more than placebo-treated one. The median time of PLT ≥ 50×109·L−1 for the first time within 6 weeks of treatment in the observation group was 3 weeks, which was the same as that in the control group. After 6 weeks of treatment, the median platelet count in the observation group was higher than that in the control group[97.50(58.25−166.75)×109·L−1 vs 45.50(13.25−82.50)×109·L−1 , P<0.05]. The median PLT count in the observation group was higher than that in the control group at week 1−6 after treatment, and the curative effect was significant. The two groups of patients tolerated the regimen well, and the degree of adverse reactions was mild, which improved quickly after symptomatic treatment. CONCLUSION Hetrombopag combined with low-dose prednison has a high effective rate in the treatment of refractory/recurrent ITP, which is better than that of single use, and the adverse reactions are tolerable, so it can be widely used in clinical practice.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Objective To investigate the effect of Angelica polysaccharides on the balance of Th17/T-regulatory(Treg)cells and the expression of related inflammatory factor proteins in the bone marrow of mice with aplastic anemia.Methods 50 male BALB/c mice were randomly divided into a normal group,model group,cyclosporine A(CsA)group,and angelica polysaccharide low-(APS-L)and high-dose(APS-H)groups.A mouse model of aplastic anemia was prepared by combining irradiation with allogeneic lymphocyte infusion.After modeling,the mice were orally administered with corresponding drugs for 28 days.The general condition,weight changes,and spleen index of the mice were observed.Blood samples were taken to test for changes in basic hematological parameters of peripheral blood,and hematoxylin and eosin staining was used to evaluate the pathological changes in mouse bone marrow tissue.An ELISA method was applied to detect bone marrow TGF-β1.The expression levels of proteins such as IL-10,IL-17A,and IL-6 were analyzed,and flow cytometry was used in detecting the bone marrow Th17/Treg cell ratio.Results Compared with the normal group,the model group mice showed clumsiness during activity;lethargy;pale eyelids,lips,and ears;and reduced food and water intake.Both body weight and spleen index were significantly decreased.Peripheral red blood cell,white blood cell,and platelet counts and hemoglobin concentration were significantly reduced.A disordered bone marrow tissue structure and significantly reduced proliferation of hematopoietic tissue were seen.The expression of IL-17A and IL-6 proteins was significantly upregulated,and the expression of TGF-β1 and IL-10 protein was significantly downregulated.The proportion of Th17 cells in bone marrow significantly increased,the proportion of Treg cells significantly decreased,and the ratio of Th17/Treg cells significantly increased(P＜0.01).Compared with the model group,the general condition of the APS-L and APS-H groups improved,showing an increase in food and water intake;a significant increase in body weight and spleen index;a significant increase in peripheral red blood cells,white blood cells,platelets,and hemoglobin concentration(P＜0.05);an improvement in bone marrow tissue structure;and an increase in hematopoietic tissue proliferation(P＜0.05).The expression of IL-17A and IL-6 proteins was significantly downregulated.The expression of TGF-β1 and IL-10 protein was significantly upregulated(P＜0.05 or P＜0.01).The proportion of Th17 cells in bone marrow significantly decreased,the proportion of Treg cells significantly increased,and the ratio of Th17/Treg cells significantly decreased(P＜0.01).Conclusions Angelica polysaccharides can improve bone marrow hematopoietic function in aplastic anemia mice,and its mechanism of action may include the regulation of Th17/Treg cell balance.

Objective:To establish a multi-factor prediction model for vascular aging based on psychological behavior and physical exercise using nomogram and structural equation method.Methods:A total of 701 inpatients or physical examination patients who underwent carotid ultrasound examination in the Affiliated Hospital of Qingdao University from October 2021 to March 2023 were selected by cross-sectional method. The subjects were randomly divided into training queue( n=492) and verification queue( n=209) according to the ratio of 7∶3.The psychological and behavioral factors, lifestyle, demography and accompanying diseases data were collected. Multi-factor binary Logistic regression method in SPSS 25.0 software was used to screen independent influencing factors of vascular aging, R 4.2.2 software was used to build a nomogram prediction model of vascular aging, and the ROC curve, calibration chart and decision curve analysis were used to evaluate the nomogram, and AMOS software was used to build a structural equation model of vascular aging. Results:Multivariate Logistic regression analysis showed that type A behavior( B=1.757, OR(95% CI)=5.790(2.750-12.210), P<0.001), physical exercise( B=-3.019, OR(95% CI)=0.050(0.020-0.100), P<0.001), high-fat diet( B=0.679, OR(95% CI)=1.970(1.350-2.880), P<0.001), sleep quality( B=-1.451, OR(95% CI)=0.230(0.120-0.460), P<0.001), tea drinking habits( B=-2.349, OR(95% CI)=0.100(0.050-0.200), P<0.001), age( B=0.061, OR(95% CI)=1.060(1.020-1.110), P=0.005), sex( B=-1.263, OR(95% CI)=0.280(0.140-0.570), P<0.001), hyperlipidemia( B=0.679, OR(95% CI)=1.970(1.350-2.880), P<0.001) and diabetes( B=0.838, OR(95% CI)=2.310(1.140-4.700), P=0.021)were independent influencing factors of vascular aging. The nomogram model showed that type A behavior, physical exercise, high-fat diet, sleep quality, tea drinking habits, age, sex, hyperlipidemia and diabetes were independent influencing factors of vascular aging.Advanced age, type A behavior, hyperlipidemia, diabetes and the score of high-fat diet were risk factors for vascular aging, while better sleep quality, tea drinking habit and the score of physical exercise were protective factors for vascular aging.Men were more prone to vascular aging than women. Structural equation model showed that type A behavior had the strongest direct positive effect on vascular aging (the effect coefficient=0.197, P<0.01), and physical exercise had the strongest direct negative effect on vascular aging (the effect coefficient=-0.452, P<0.01), which could indirectly affect vascular aging through various factors. Conclusions:The nomogram model shows the independent influencing factors of vascular aging and has certain predictive value.Structural equation model shows that many factors such as psychological behavior and lifestyle can directly or indirectly affect the occurrence of vascular aging, among which type A behavior and physical exercise have more extensive effects.

Objective To establish the reference intervals of neutrophil to lymphocyte ratio(NLR),mono-cyte to lymphocyte ratio(MLR)and platelet to lymphocyte ratio(PLR)in different genders and age groups in northern Chinese adults.Methods The data were analyzed according to the Clinical and Laboratory Stand-ards Institute C28-A3.Outliers were checked and judged according to the Dixon method.Subgroups were di-vided according to gender or age factors,and reference intervals were established for different subgroups.Ref-erence intervals were expressed as two-sided 95％percentiles.Results The reference intervals of NLR,MLR and PLR were 0.90-3.82,0.09-0.33 and 71.20-246.87,respectively.The results showed that NLR and PLR in men were lower than those in women(P＜0.001),while MLR in men was significantly higher than that in women(P＜0.001).Linear trend plots showed that NLR,MLR and PLR changed significantly in dif-ferent genders and age groups.In men,NLR and MLR increased with age,while PLR gradually increased and reached the peak before 50 years old,and gradually decreased after 50 years old.In women,NLR and MLR showed the lowest values at 50-＜60 years old,while PLR reached the peak at about 50 years old.The refer-ence intervals established by the model set were verified,and the percentages beyond the reference intervals were less than 10％in different genders and age groups.Conclusion The reference intervals of NLR,MLR and PLR in different genders and age groups of healthy adults in northern China are established in the study.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven-tion of neurobehavioral development delays in young children.Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pe-diatric Heart Scale)with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays,and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale,the basic information of the young children and their mothers at the time of birth were investigated,as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected.Results A total of 271 young children were included,196 males and 75 females.Young children had the lowest developmental quotient(DQ)in the language domain among the five domains(P＜0.001).Multiple lin-ear regression models showed:compared with girls,the language domain DQ of boys decreased by 5.321 points(P=0.049,95％CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95％CI:-8.316--0.631).Compared with young children via natural vaginal delivery(NVD),the gross motor domain DQ of young children via caesarean section(CS)decreased by 4.890 points(P=0.008,95％CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95％CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95％CI:-12.826--2.416),per-sonal-social domain DQ decreased by 6.232 points(P=0.001,95％CI:-10.006--2.457).The results of bi-nary logistic regression models showed,compared with young children via NVD,the risk of gross motor domain retar-dation in young children increased(OR=1.763,95％CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95％CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95％CI:1.080-10.124).Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains,boys had lower DQ in language domain and personal-social domain than girls,and the development of young children via CS was slower than that via NVD.Fo-cus should be on the language development of young children especially on the language and personal-social devel-opment of boys.Carefully chose delivery way.Focus should be placed on assessment of young children's comprehen-sive neurobehavioral development in early time.