BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.

Objective To investigate the therapeutic effect of Euryale ferox seed shell extract on oral ulcer in rats and its underlying mechanism. Methods The contents of polyphenols and flavonoids in Euryale ferox seed shells were determined by Folin-phenol assay and aluminum nitrate colorimetry, respectively. DPPH · , ABTS+· , · OH and · O2- scavenging experiments were performed to evaluate the antioxidant activities of Euryale ferox seed shell extract in vitro. In a rat model of oral ulcer induced by burning with glacial acetic acid, the therapeutic effect of Euryale ferox seed shell extract was assessed by detecting changes in serum levels of oxidative factors by enzyme-linked immunosorbent assay (ELISA) and observing pathological changes of the ulcerous mucosa using HE staining; the therapeutic mechanism of the extract was explored by detecting the expression levels of Keap1, Nrf2, Nes-Nrf2 and HO-1 proteins in ulcerous mucosa using Western blotting. Results The ethyl acetate extract of Euryale ferox seed shells contained 306.74±1.04 mg/g polyphenols and 23.43±0.61 mg/g flavonoids and had IC50 values for scavenging DPPH · and ABTS+· free radicals of 3.42 ± 0.97 μg/mL and 3.32 ± 0.90 μg/mL, respectively. In the rat models, the ethyl acetate extract significantly ameliorated oral mucosal ulcer, increased serum CAT level, and decreased serum MDA level. The protein expression levels of Nes-Nrf2 and HO-1 were increased and Keap1 protein expression was lowered significantly in the ulcerous mucosa of the rats after treatment with the extract (P<0.05 or 0.01). Conclusion The therapeutic effect of Euryale ferox seed shell extract on oral ulcers in rats is mediated probably by activation of the Keap1/Nrf2/HO-1 signaling pathway.

Objective To investigate the mechanism by which conbercept reverses transforming growth factor-β2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(HLECs).Methods Cultured HLEC SRA01/04 cells were treated with TGF-β2,conbercept,or both,and the changes in cell proliferation,apoptosis,and migration were observed using MTT assay,flow cytometry,scratch assay,and Transwell assay.Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers(E-Cadherin,α-SMA,and Snail),extracellular matrix components,and genes related to the TGF-β/Smad signaling pathway.Results Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells,decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA,Snail,collagen I,collagen IV,and FN1,and upregulated the protein and mRNA expressions of E-cadherin(P<0.05).Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group(P<0.05).Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT(P<0.01).Conclusion Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway,indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.