AIM To study the chemical constituents from the leaves of Drynaria fortunei(Kunze)J.Sm.and their antioxidant activity.METHODS ODS-AG-HG,Sephadex LH-20 and semi-preparative HPLC were used for separation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH mothod.RESULTS Fifteen compounds were isolated and identified as kaempferol-3-O-neohesperidoside(1),dihydrodehydrodiconiferyl alcohol(2),kaempferol-3,7-di-O-α-L-rahmnoside(3),astragalin(4),loliolid(5),trichothecene analogue(6),2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane(7),maculatin(8),trichothecin(9),4-[(Z)-but-2-enoyloxy]-8-chloro-12-hydroxy-7,13-epoxytrichothec-9-ene(10),8-deoxy-trichotecin(11),β-sitosterol(12),daucosterol(13),afzelin(14),samwinol(15).The IC50 values of the leaf and rhizome extracts against DPPH free radicals were(0.072±0.005),(0.287±0.012)mg/mL,respectively.CONCLUSION Compounds 1,2,5-11,15 are isolated from this plant for the first time.The leaves of D.fortunei exhibit strong antioxidant activity.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P＜0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.

Aim To investigate the expression of al-pha-enolase 1(ENO1)in FLT3-mutated acute myeloid leukemia(AML)and its impact on prognosis,as well as to assess the influence of ENO1 on the antitumor effects of FLT3 inhibitors.Methods Data from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed to compare the expression differences of ENO1 in various tumors and normal tissues.ENO1 knockdown cells were con-structed using the AML cell line MOLM13.The impact of ENO1 on AML cell proliferation,apoptosis,and drug sensitivity was evaluated through CCK-8 assays,flow cytometry,drug synergy experiments,transcriptome se-quencing,and lipid peroxide and reactive oxygen spe-cies(ROS)levels were detected.Results The ex-pression level of ENO1 was significantly elevated in FLT3 internal tandem duplication mutation(FLT3-ITD)positive AML patients and was associated with poor prognosis.Knockdown of ENO1 significantly in-hibited AML cell proliferation and induced apoptosis.Inhibition of ENO1 significantly increased the chemo-sensitivity of AML cells to FLT3 inhibitors.Transcrip-tome sequencing analysis revealed differential expres-sion of genes in the NADPH oxidase-related pathway following ENO1 knockdown,and a positive correlation between ENO1 and glutathione peroxidase 4(GPX4)expression.Inhibition of ENO1 significantly increased the levels of lipid peroxides and ROS induced by FLT3 inhibitors.Conclusions High expression of ENO1 is significantly associated with poor prognosis in FLT3(+)AML.Inhibition of ENO1 can enhance the anti-tumor effects of FLT3 inhibitors by regulating the an-tioxidant defense capacity of AML cells,providing a new target and therapeutic strategy for the treatment of FLT3/ITD(+)AML.

Aim To investigate the expression of al-pha-enolase 1(ENO1)in FLT3-mutated acute myeloid leukemia(AML)and its impact on prognosis,as well as to assess the influence of ENO1 on the antitumor effects of FLT3 inhibitors.Methods Data from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed to compare the expression differences of ENO1 in various tumors and normal tissues.ENO1 knockdown cells were con-structed using the AML cell line MOLM13.The impact of ENO1 on AML cell proliferation,apoptosis,and drug sensitivity was evaluated through CCK-8 assays,flow cytometry,drug synergy experiments,transcriptome se-quencing,and lipid peroxide and reactive oxygen spe-cies(ROS)levels were detected.Results The ex-pression level of ENO1 was significantly elevated in FLT3 internal tandem duplication mutation(FLT3-ITD)positive AML patients and was associated with poor prognosis.Knockdown of ENO1 significantly in-hibited AML cell proliferation and induced apoptosis.Inhibition of ENO1 significantly increased the chemo-sensitivity of AML cells to FLT3 inhibitors.Transcrip-tome sequencing analysis revealed differential expres-sion of genes in the NADPH oxidase-related pathway following ENO1 knockdown,and a positive correlation between ENO1 and glutathione peroxidase 4(GPX4)expression.Inhibition of ENO1 significantly increased the levels of lipid peroxides and ROS induced by FLT3 inhibitors.Conclusions High expression of ENO1 is significantly associated with poor prognosis in FLT3(+)AML.Inhibition of ENO1 can enhance the anti-tumor effects of FLT3 inhibitors by regulating the an-tioxidant defense capacity of AML cells,providing a new target and therapeutic strategy for the treatment of FLT3/ITD(+)AML.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Hospitals worldwide recognise the importance of data and digital transformation in healthcare. We traced a smart hospital's data-driven journey to build an artificial intelligence and digital ecosystem (AIDE) to achieve healthcare excellence. We measured the impact of data and digital transformation on patient care and hospital operations, identifying key success factors, challenges, and opportunities. The use of data analytics and data science, robotic process automation, AI, cloud computing, Medical Internet of Things and robotics were stand-out areas for a hospital's data-driven journey. In the future, the adoption of a robust AI governance framework, enterprise risk management system, AI assurance and AI literacy are critical for success. Hospitals must adopt a digital-ready, digital-first strategy to build a thriving healthcare system and innovate care for tomorrow.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Hospitals ; Cloud Computing ; Robotics ; Internet of Things ; Data Science

Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P＜0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.