With the continuous advancement of healthcare informatization,medical data,closely related to people's health,has experienced explosive growth.On one hand,the interoperability of hospitals and the construction of smart hospitals have laid a solid foundation for the application of medical big data.On the other hand,the surge in data volume demands increas-ingly higher data processing capabilities.Effectively organizing and managing medical data across various stages—such as collec-tion,storage,governance,and service—using technologies like data mining,data governance,deep learning,and big data visu-alization has become an urgent need.This paper addresses existing hospital management issues by constructing a medical big data information platform,exploring its innovative applications in hospital management,and proposing future development suggestions for the platform.The aim is to enhance the digitalization of medical management and promote the application and development of big data technology in the healthcare field.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.
Biological Products/chemistry* ; Catalysis ; Alkaloids ; Biocatalysis

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Network Pharmacology ; Rats ; Seeds/chemistry* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Tandem Mass Spectrometry ; Ziziphus/chemistry*

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

ObjectiveTo investigate effect of aqueous extract of Trametes robiniophila （TRM，Huaier） on autophagy of human prostate cancer VCaP cells and Lamin B₁ expression， so as to uncover its role in the proliferation of VCaP cells. MethodThe inhibitory effect of 0， 2， 4， 6， 8， 10 g·L^-1 TRM aqueous extract on the proliferation of human prostate cancer VCaP cells at different time points were determined by cell counting kit-8 （CCK-8） assay. Acridine orange staining was conducted for analyzing the effect of TRM aqueous extract on the formation of autolysosomes in VCaP cells. After medication， the expression of microtubule-associated protein Ⅰ light chain 3 （LC3）， autophagy-related protein 3 （Atg3）， autophagy-related protein 5 （Atg5）， and autophagy-related protein 7 （Atg7） in VCaP cells were detected by Western blot. The effect of TRM aqueous extract alone and its combination with autophagy inhibitor bafilomycin A₁ on the proliferation of VCaP cells were assayed by CCK-8 assay. RNA interference technology was used to explore the role of Lamin B₁ in anti-proliferation of VCaP cells by TRM. ResultCompared with the blank group， TRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells in a time- and concentration-dependent manner （P<0.01）. Acridine orange staining showed that TRM aqueous extract promoted the formation of autolysosomes in VCaP cells. As revealed by Western blotting， TRM aqueous extract up-regulated the expression levels of LC3-Ⅱ， Atg3， Atg5， and Atg7 in contrast to those in the blank group （P<0.05）. All these indicated that TRM aqueous extract induced the autophagy of VCaP cells. In addition， autophagy inhibition impaired the sensitivity of VCaP cells to TRM aqueous extract （P<0.05）. The comparison with the blank group showed that TRM aqueous extract inhibited Lamin B₁ protein expression in VCaP cells （P<0.01）， which in turns weakened the sensitivity of VCaP cells to TRM aqueous extract. ConclusionTRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells possibly by inducing autography and down-regulating Lamin B₁ expression. This study has provided a theoretical basis for the clinical application of TRM.

ObjectiveTo explore the effect of Chaishao Liujuntang on Hedgehog signaling pathway in rats with chronic atrophic gastritis （CAG） of liver depression and spleen deficiency. MethodWistar rats were randomized into normal group and modeling group. CAG with the liver depression and spleen deficiency syndrome was induced in rats in the modeling group with a compound method. After modeling， they were classified into the model group， vitacoenzyme group， Chaishao Liujuntang group， GDC-0449 （blocker） group， and Chaishao Liujuntang + GDC-0449 group. Normal group and model group were given （ig） normal saline. Vitacoenzyme and Chaishao Liujuntang group received （ig） corresponding drugs at 240 mg·kg^-1·d^-1 and 5.1 g·kg^-1·d^-1， respectively， and GDC-0449 group was treated （ip） with GDC-0449 at 50 mg·kg^-1·d^-1. For the Chaishao Liujuntang + GDC-0449 group， rats received GDC-0449 （ip） at 50 mg·kg^-1·d^-1 and Chaishao Liujuntang （ig） at 5.1 g·kg^-1·d^-1. The administration lasted 4 weeks. The pathological morphology of rat gastric mucosa was observed based on hematoxylin-eosin （HE） staining. mRNA and protein expression of sonic hedgehog （Shh）， 12th transmembrane receptor Patched1 （Ptch1）， and glioma-associated oncogene homolog 1 （Gli1） in gastric mucosa tissues was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot. Content of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with normal group， the model group demonstrated decrease in gland cells， glandular atrophy， large lumen volume， plasma cell infiltration， intestinal metaplasia， decrease in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa （P<0.01）， and rise of serum IL-1β and TNF-α content （P<0.01）. Compared with model group， vitacoenzyme group and Chaishao Liujuntang group showed ordered cells， alleviation of gland atrophy， and no obvious inflammatory infiltration， and GDC-0499 group and Chaishao Liujuntang + GDC-0449 showed no significant improvement. Significant rise in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa tissues of vitacoenzyme group and Chaishao Liujuntang group （P<0.01）， no significant difference in serum IL-1β content and significant decrease in TNF-α content in vitacoenzyme group （P<0.01）， significant reduction in content of serum IL-1β and TNF-α in Chaishao Liujuntang group （P<0.05， P<0.01） were observed compared with those in the model group. The mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa and the content of serum IL-1β and TNF-α were insignificantly different between the GDC-0449 group and Chaishao Liujuntang + GDC-0449 group. ConclusionChaishao Liujuntang can effectively improve the pathological state of gastric mucosa in CAG rats with liver depression and spleen deficiency， which may be related to the activation of Hedgehog signaling pathway and the decrease of IL-1β and TNF-α content.

Aim To investigate the expression of Foxos in human umbilical vein endothelial cells(HUVECs)with insulin resistance(IR)induced by high glucose and high fat(HG/HF)stress and its significance.Methods First, the IR model of endothelial cells was established by HG /HF stress.The differential expression of Foxos gene in normal(Ctrl )group and HG /HF group was observed, and the subtypes with the most significant changes in Foxos were screened out, such as Foxo6.Next, Foxo6 was silenced to observe its role in endothelial cell with IR.Finally, whether the mechanism of Foxo6-mediated IR was related to the interaction of NF-κB signaling was investigated.Results The expression increase of Foxo6 was the most significant among Foxos under the IR condition induced by HG/HF.Using a small RNA interference and plasmid transfection technique, we found that the silence effect of the siRNA3 fragments targeting Foxo6 was the most significant among the siRNAs.Moreover, the further study showed that silencing the Foxo6 gene could significantly reverse the endothelial IR induced by HG/HF, and the mechanism of the reversal effect was related to the interaction between the Foxo6 and NF-κB signal.Conclusions Foxo6 mediates the endothelial cell IR induced by the HG /HF stress.The underlying mechanism is that Foxo6 can interact with NF-κBp65 and activate NF-κB signaling pathway.Silencing Foxo6 can improve the IR of vascular endothelial cells induced by HG /HF stress.