OBJECTIVE To improve the inventory turnover rate of traditional Chinese medicine （TCM） decoction pieces in hospitals and achieve refined inventory management for cost reduction and efficiency improvement. METHODS Inventory data of TCM decoction pieces in our hospital from 2022 to 2023 were collected. Based on the sale amount and demand coefficient of variation respectively， the ABC classification method and XYZ analysis method were adopted for classification. The two classification results were combined through a cross matrix to divide them into three-level management priorities： level Ⅰ （AX， AY， BX）， level Ⅱ （AZ， BY， CX）， and level Ⅲ （BZ， CY， CZ）. Differentiated inventory strategies were formulated for each level， and core indicators such as turnover rate and inventory cost before and after inventory management optimization were compared. RESULTS There were 58 types （14.22%） in level Ⅰ， 85 types （20.83%） in level Ⅱ， and 265 types （64.95%） in level Ⅲ. After inventory management optimization， the average inventory value of TCM decoction pieces decreased by 341 800 yuan， the average turnover rate increased by 73.03%， and the average turnover days decreased by 4.98 days. The differences in all indicators before and after optimization were statistically significant （ P ＜0.01）. CONCLUSIONS The ABC-XYZ analysis method can break through the single-dimensional limitation of the traditional ABC classification method， adapt to characteristics such as the strong seasonality of TCM decoction pieces， significantly optimize the inventory structure， improve turnover efficiency， and reduce operating costs. It provides a feasible plan for the refined and scientific management of hospital TCM warehouses.

Objective:This study aimed to identify key genes in endothelial cell (EC) associated with the pathogenesis and progression of human venous malformations (VMs) through bioinformatics analysis, providing potential biomarkers for early screening and targeted therapy of VMs.Methods:A case-control study was conducted using surgically resected tissue specimens from VMs patients at the Third Affiliated Hospital of Zhengzhou University (from September 2021 to September 2023), with malformed venous tissues as the experimental group and distal normal venous tissues as controls. Single-nucleus RNA sequencing (snRNA-seq) was performed on paired experimental and control samples from four VM patients. High-dimensional weighted gene co-expression network analysis (hdWGCNA), combined with gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) network analysis, identified critical genes. Validation experiments included 15 additional VM cases and controls using reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blot.Results:A total of 55 430 nuclei were captured using snRNA-seq, with 30 391 nuclei from the experimental group and 25 039 nuclei from the control group. Cluster analysis identified 22 distinct cell populations, which were annotated into 8 cell types. hdWGCNA revealed four modules associated with invasion, which were enriched in angiogenesis, integrin signaling, and cell adhesion according to GO analysis. KEGG pathway analysis indicated that the PI3K-AKT signaling pathway and focal adhesion are key regulatory mechanisms. PPI network analysis combined with cytoscape identified EGFL7, TEK, and FLT1 as key genes. RT-qPCR results demonstrated that the relative mRNA expression levels of these three genes in the experimental group (6.66±2.31, 1.86±0.62, 3.49±0.58) were significantly higher than those in the control group (1.05±0.14, 1.00±0.14, 1.06±0.25), with statistically significant differences ( t=9.37, 4.27, 11.20, P<0.05). Immunohistochemical analysis showed that the relative protein expression levels of these three genes in the cytoplasm of the experimental group (0.84±0.15, 0.68±0.14, 0.85±0.12) were also significantly higher than those in the control group (0.19±0.05, 0.23±0.06, 0.30±0.05), with statistically significant differences ( t=16.62, 5.93, 11.68, P<0.05). Western blot analysis confirmed that the relative protein expression levels of these three genes in the experimental group (0.35±0.04, 0.36±0.09, 0.31±0.04) were significantly higher than those in the control group (0.19±0.01, 0.13±0.02, 0.14±0.04), with statistically significant differences ( t=7.05, 4.61, 5.93, P<0.05). Conclusion:EGFL7, FLT1, and TEK in EC may play crucial roles in the occurrence and invasion of VMs.

To investigate the role of the DPP4-nestin axis in liver fibrosis induced by alveolar cyst infection,a murine model was established using C57BL/6 mice via hepatic portal vein injection.Liver histopathological changes were assessed using HE staining,while immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of nestin and DPP4 in infected mouse livers.In vitro,J S1 cell line was stimulated with recombinant DPP4 protein to es-tablish a cellular model,and qPCR,Western blot,and shRNA lentivirus interference techniques were utilized to examine the involvement of the DPP4-nestin axis in hepatic stellate cell activation.The findings demonstrated that compared to the Sham group,liver tissue structure disruption and collagen deposition were evident along with significantly increased expressions of nestin and DPP4(P＜0.050 0),which colocalized with nesin and α-SMA.Furthermore,stimulation with recombi-nant DPP4 protein significantly enhanced JS1 cell activation(P＜0.050 0)as well as upregulated nestin expression(P＜0.050 0)when compared to control group cells.Notably,shRNA lentivirus-mediated inhibition of nestin expression effectively suppressed the activating effects exerted by re-combinant DPP4 protein on JS1 cells(P＜0.050 0).Collectively,these results highlight the crucial regulatory role played by the DPP4-nestin axis in hepatic stellate cell activation triggered by alveo-lar infection;thus,targeting this axis may represent a novel therapeutic strategy for treating alveo-lar infection-induced liver fibrosis.

Objective:To explore the effect of sacubitril/valsartan(LCZ696)on intestinal microbiota and serological parameters associ-ated with its derived metabolites in rats with right ventricular remodeling due to hypoxic pulmonary hypertension(HPH).Methods:A total of 24 male rats were randomly divided into Control group,Hypoxia group,and H-LCZ696 group.Since day 1,the rats in the H-LCZ696 group were given LCZ696 by gavage,while those in the other two groups were given normal saline by gavage,both for 4 con-secutive weeks.Related indicators were measured after experiment,including hemodynamics,color Doppler ultrasound of right heart,and right ventricular remodeling.Histopathological staining and transmission electron microscopy were used to observe tissue struc-tures;the metagenomics technique was used to analyze the characteristics and functional annotation of intestinal microbiota in the fe-ces of the rats;ELISA was used to measure the serological parameters of the metabolites derived from intestinal microbiota.Results:There was a significant difference in mean pulmonary arterial pressure(mPAP)between the three groups of rats(F=101.797,P=0.000).Compared with the Control group,the Hypoxia group had an increase in mPAP,a reduction in right ventricular function,and in-creases in the indicators for pulmonary vascular remodeling and right ventricular remodeling.Compared with the Hypoxia group,the H-LCZ696 group had a reduction in mPAP,an improvement in right ventricular function,and reductions in the indicators for pul-monary vascular remodeling and right ventricular remodeling.Trans-mission electron microscopy showed that the Hypoxia group had disordered myocardial myofibrils of the right ventricle and mitochon-drial swelling,while such ultrastructural damage was improved after LCZ696 intervention.The metagenomics analysis showed that the Hypoxia group had a reduction in the diversity of intestinal microbiota,with increases in the abundance of pathogenic bacteria(such as Proteobacteria,Prevotella,and Clostridium)and reductions in the abundance of probiotic bacteria(such as Lachnospiraceae and Lacto-bacillus),and such changes were partially reversed after LCZ696 intervention,with inhibition of the proliferation of pathogenic bacteria such as Clostridiales,the failure to restore the diversity of intestinal microbiota,and a further reduction in the abundance of some probi-otic bacteria(such as Lactobacillus).ELISA showed that compared with the Control group,the Hypoxia group had increases in the serum levels of pro-inflammatory metabolites,and compared with the Hypoxia group,the H-LCZ696 group had reductions in the se-rum levels of pro-inflammatory metabolites.Conclusion:LCZ696 can alleviate right ventricular remodeling in HPH and regulate pathogenic bacteria and serum pro-inflammatory metabolites,with a main therapeutic effect on the cardiovascular system and a regula-tory effect on intestinal microbiota.

Objective To explore the active monitoring strategies for hypoglycemia in hospitalized dia-betic patients,as well as their clinical symptom characteristics and influencing factors.Methods A retrospec-tive search was conducted on all inpatients in a tertiary hospital in 2023.The hospital's electronic medical re-cord system was manually retrieved through the inpatient numbers of the patients.Adult inpatients with dia-betes who experienced hypoglycemia were included as the research subjects,and the general conditions and possible hypoglycemia-related risk factors were collected.Embed the hypoglycemic electronic trigger program in China Hospital Pharmacovigilance System(CHPS),reviewed the original medical records of patients with positive trigger triggering,and calculated the positive predictive value(PPV).Searched for the number of hy-poglycemic adverse reaction cases voluntarily reported by this hospital during the same period from National Adverse Reaction Monitoring System and compared with the actual number of hypoglycemic cases discovered.Patients with suspected drug-induced hypoglycemia were divided into the symptomatic group and the asymp-tomatic group based on whether they presented hypoglycemia-related symptoms.Multivariate logistic regres-sion analysis was applied to analyze the influencing factors.Results A total of 1 001 adult hospitalized diabet-ic patients with hypoglycemia were included in the study.Among them,725 cases were suspected of drug-in-duced hypoglycemia,and 495 cases were suspected of hypoglycemia caused by drug interactions.After manual review,131 cases of drug-induced hypoglycemia patients had clinical symptoms,and hypoglycemic adverse re-action events should be reported,PPV of this trigger for symptomatic hypoglycemia was 18.1%(131/725).However,the number of hypoglycemic adverse reactions spontaneously reported through National Adverse Reaction Monitoring System by this hospital during the same period was 4 cases,and the reporting rate was only 3.1%(4/131).Multivariate logistic regression analysis showed that aging and grade 2 hypoglycemia were risk factors for the occurrence of related symptoms in patients with suspected drug-induced hypoglycemia(P<0.05),while surgery,type 2 glucosuria,unclassified diabetes,and the use of insulin secretagogues were protective factors(P<0.05).Conclusion Drug-induced hypoglycemia dominates among hospitalized diabetic patients,and age,hypoglycemia grade,inpatient department using insulin secretagogues,diabetes diagnosis and classification are closely related to the occurrence of clinical hypoglycemia-related symptoms.Active monito-ring through CHPS can effectively increase the detection rate and reporting rate of hypoglycemic adverse e-vents in hospitalized diabetic patients.

Objective To investigate the correlation between serum homeodomain interacting protein ki-nase 2(HIPK2),annexin A5(ANXA5)and coronary stenosis and prognosis in patients with acute myocardial infarction(AMI).Methods A total of 277 AMI patients who received interventional treatment in this hospi-tal from January 2021 to July 2023 were selected as the AMI group,and another 140 cases with normal or very mild stenosis in coronary angiography during the same period were selected as the control group.According to the degree of coronary artery stenosis(Gensini score),the AMI patients were divided into mild coronary arter-y stenosis group(86 cases),moderate coronary artery disease group(111 cases)and severe coronary artery disease group(80 cases).According to the prognosis,they were divided into poor prognosis group(80 cases)and good prognosis group(197 cases).Enzyme-linked immunosorbent assay was used to detect the serum HIPK2 and ANXA5 levels.Spearman correlation analysis was used to analyze the correlation between serum HIPK2 and ANXA5 levels and Gensini score in patients with AMI.Multivariate unconditional Logistic regres-sion was used to determine the relationship between serum HIPK2 and ANXA5 levels and prognosis of AMI patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficiency of serum HIPK2 and ANXA5 levels on prognosis of AMI patients.Results Compared with the control group,the ser-um HIPK2 level in the AMI group increased and the ANXA5 level decreased,and the differences were statisti-cally significant(P＜0.05).The serum HIPK2 levels in the mild coronary artery stenosis group,moderate coronary artery stenosis group and severe coronary artery stenosis group increased successively,while the ANXA5 levels decreased successively,and the differences were statistically significant(P＜0.05).Gensini score was positively correlated with serum HIPK2 level and negatively correlated with serum ANXA5 level in AMI patients(P＜0.05).The Gensini score of AMI patients was positively correlated with the serum HIPK2 level(r=0.785,P＜0.05),and negatively correlated with the serum ANXA5 level(r=-0.798,P＜0.05).Compared with the good prognosis group,the serum HIPK2 level in the poor prognosis group increased(P＜0.05),and the ANXA5 level decreased(P＜0.05).After adjusting for confounding factors,high HIPK2 was an independent risk factor for poor prognosis in AMI patients(P＜0.05),and high ANXA5 was an independ-ent protective factor(P＜0.05).The area under the curve of the combined prediction of serum HIPK2 and ANXA5 levels for the prognosis of AMI patients was 0.875,which was greater than 0.778 and 0.784 predic-ted by serum HIPK2 and ANXA5 levels alone(P＜0.05).Conclusion The serum HIPK2 level is increased and the ANXA5 level is decreased in patients with AMI,which is related to the aggravation of coronary steno-sis and the poor prognosis.The combination of serum HIPK2 and ANXA5 levels is more effective in predic-ting the prognosis of patients with AMI.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.