Digital medical insurance governance， as an important component of digital transformation， improves the efficiency of medical insurance services while facing complex ethical challenges. Taking stakeholder theory as the analytical framework， this paper explored the generative mechanisms， manifestations， and countermeasures of ethical issues in digital medical insurance governance. This study uncovered that accelerated technological iteration and lagging ethical and legal norms， as well as interest conflicts among multiple participants in governance， constituted the major causes of ethical issues. These issues specifically manifested as data privacy leakage， unfair algorithmic decision-making， widening digital divide， ambiguous accountability， and other aspects. To address these issues， this paper put forward systematic countermeasures， such as establishing a dynamic ethical and legal regulatory system， balancing the demands of stakeholders， strengthening technological ethical governance， narrowing the digital divide， and enhancing accountability mechanisms. Through the implementation of multi-dimensional governance strategies， it aimed to balance technological innovation and ethical constraints， advance the inclusiveness， fairness， and sustainable development of digital medical insurance， and provide theoretical reference and practical references for improving China’s digital medical insurance governance system.

Objective: To investigate the effect and mechanism of resveratrol-derived carbonized polymer dots (RSV-CPDs) on macrophage polarization and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions, and to provide an experimental basis for the treatment of periodontitis with RSV-CPDs. Methods: RSV-CPDs were prepared by high-temperature pyrolysis of resveratrol (RSV) in the presence of ammonia as a catalyst, and RSV-CPDs were characterized by transmission electron microscope (TEM), Fourier transform infrared spectrometer (FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). CCK8 was used to detect the cytotoxicity of RSV-CPDs. The effects of RSV-CPDs on the apoptosis and cell polarization of macrophages stimulated by Porphyromonas gingivalis-lipopolysaccharide (P.g-LPS) were detected by flow cytometry: ① For the apoptosis detection experiment, the macrophages (RAW264.7) were divided into the control group (no treatment), P.g-LPS group [treated with P.g-LPS (2 μg/mL) for 24 h], RSV group [treated with P.g-LPS (2 μg/mL) + RSV (10 μg/mL) for 24 h], and RSV-CPDs group [treated with P.g-LPS (2 μg/mL) + RSV-CPDs (50 μg/mL) for 24 h]. ② For the cell polarization experiment, the macrophages (RAW264.7) were divided into four groups. They were the control group (no treatment), P.g-LPS + IFN-γ group [P.g-LPS (200 ng/mL) + IFN-γ (20 ng/mL) treated cells for 24 h], RSV group [P.g-LPS (200 ng/mL) + IFN-γ (20 ng/mL) + RSV (10 μg / mL) treated cells for 24 h], RSV-CPDs group [P.g-LPS (200 ng / mL) + IFN-γ (20 ng / mL) + RSV-CPD (50 μg / mL) treated cells for 24 h]. The supernatant of macrophages in the above four groups of cell polarization experiments was collected and mixed with osteogenic induction medium at a 1:1 ratio to culture hPDLSCs. The hPDLSCs were divided into the control group, P.g-LPS + IFN-γ group, RSV group, and RSV-CPDs group. The osteogenic trend of hPDLSCs was detected by alkaline phosphatase (ALP) staining and alizarin red staining (ARS). Real-time quantitative PCR (RT-qPCR) was used to detect the expression of osteogenesis-related genes. Western blot was used to detect the expression of osteogenesis-related proteins in hPDLSCs. Finally, transcriptome tests were used to explore the mechanism of the effect of RSV-CPDs on the phenotype of macrophages (THP-1) stimulated by inflammation. Results: TEM results showed that RSV-CPDs exhibited a uniform spherical structure. FTIR results showed the O-C=O peak of RSV-CPDs. XRD results confirmed that the newly synthesized RSV-CPDs exhibited an amorphous structure. XPS results showed that RSV-CPDs formed a hydrophilic carboxyl group. CCK-8 results showed that RSV had specific toxicity to RAW264.7 when the concentration exceeded 10 μg/mL (P = 0.011), while RSV-CPDs still had good biosafety to cells when the concentration reached 50 μg/mL (P > 0.05). Therefore, the concentration of RSV was 10 μg/mL and RSV-CPDs was 50 μg/mL. The results of flow cytometry showed that RSV-CPDs inhibited the apoptosis of macrophages under inflammatory stimulation (P = 0.008), and the inhibitory effect was better than that of its precursor RSV (P = 0.009). Compared with the P.g-LPS + IFN-γ group, CD86+ cells in the RSV group and RSV-CPDs group decreased by varying degrees (P < 0.001, P = 0.004), while CD206+ cells increased by varying degrees (P = 0.006, P = 0.008), and the proportion of CD206+ cells in the RSV-CPDs group was higher than that in the RSV group (P = 0.010). Compared with the P.g-LPS + IFN-γ group, the supernatant of macrophages treated with RSV-CPDs significantly increased the ALP expression (P = 0.005) and ARS level (P = 0.006) of hPDLSCs. The mRNA expression of osteogenic-related genes RUNX-2, OCN, and COL-1 significantly increased (P < 0.05), and the level of RUNX-2 protein also significantly increased (P = 0.001). Transcriptome results showed that compared with the P.g-LPS + IFN-γ group, the nuclear factor kappa-B (NF-κB) signaling pathway and tumor necrosis factor (TNF) signaling pathway in the RSV-CPDs group showed downward trends. Conclusion RSV-CPDs can inhibit the apoptosis of macrophages in the inflammatory state, promote M2 polarization, and bolster the osteogenic differentiation of hPDLSCs. The mechanism involved may be related to the inhibition of NF-κB and TNF signaling pathways.

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Objective To understand the distribution characteristics of fungi on object surface in hospital environ-ment,and provide reference for the scientific and precise formulation of environment control strategies based on fun-gal in clinic.Methods From December 7 to 23,2023,a total of 60 environmental specimens of 19 categories in 6 departments of a large tertiary first-class hospital were collected and divided into water-related environmental speci-men group,complete facade environmental specimen group,and sanitary ware environmental specimen group.18S rRNA sequencing was performed on specimens with fungi detected.Results Fungal detection rate of environmental specimens was 20.00％(12/60).Sink in the department of endocrinology had the highest fungal colony count(15 CFU/cm2),followed by the air outlet of air disinfection device in the department of thoracic surgery and the in-ternal part of a faucet in the department of endocrinology(both 10 CFU/cm2).The water-related environmental specimen group detected most diverse fungal genera(14 species),with high relative abundances of Aspergillus(100％),Meyerozyma(99.06％),Ophiocordyceps genus(95.63％),and Kodamaea(87.86％).The air outlet of air disinfection device was detected with a high abundance of Chaetomium(44.08％)and Corollospora(39.71％).There was no statistically significant difference in the α-diversity(Shannon and Simpson indices,P values of 0.661 and 0.568,respectively)and β-diversity(P=0.712)among the three environmental specimens.Conclusion Under the routine implementation of basic environmental cleaning and disinfection in medical institutions,fungi are in a low prevalence in the environment.However,moist surfaces and air disinfection device are prone to fungal colonization,and it is necessary to strengthen daily monitoring and take corresponding intervention measures to reduce the risk of infection.

Objective To observe the effects of general anesthesia with remazolam on electrophysiological monitoring indicators and cerebral oxygen saturation(ScO2)in patients undergoing carotid endarterectomy(CEA).Methods Patients who underwent elective CEA from July 2022 to June 2024 in neurosurgery department of our hospital were randomly divided into the ramazolam group(R group)and the propofol group(P group).Patients in both groups were given propofol 1.5 to 2.0 mg/kg,cisatracurium 0.1 to 0.2 mg/kg,and sufentanil 0.3 to 0.4 μg/kg for anesthesia induction.Anesthesia maintenance:patients in the R group received intravenous infusion of remifentanil 0.5 to 1.0 mg·kg-1·h-1,while patients in the P group received intravenous infusion of propofol 5.0 to 7.0 mg·kg-1·h-1.Both groups received intravenous infusion of remifentanil 0.1 to 0.2 μg·kg-1·min-1 for anesthesia maintenance.The operation time,carotid artery occlusion time,intraoperative infusion volume,remifentanil and norepinephrine dosage,and awakening time of patients in the two groups were recorded.The hemodynamic and cerebral oxygen indicators,amplitude and latency of evoked potentials before anesthesia(T0),after anesthesia(T1),5 minutes before blockade(T2),5 minutes after blockade(T3),5 minutes after unblocking(T4)and at the end of surgery(T5)of patients in the two groups were observed and compared,and the total incidence of postoperative complications was followed up and calculated.Results Compared with the P group,the dosage of intraoperative norepinephrine of patients in the R group was reduced(P<0.05),and the awakening time was shortened(P<0.05).At T2,the average arterial pressure(MAP)of patients in the R group was higher than that in the P group(P<0.05).At T3,the ScO2 of patients in the R group was significantly higher than that in the P group,and the percentages of prolonged latency and decreased amplitude of motor evoked potentials(MEP)were significantly lower than those in the P group(P<0.05),the percentage of decreased amplitude of lower limb somatosensory evoked potentials(SSEP)was lower than that in the P group(P<0.05);At T5,the MEP amplitude of patients in the R group was significantly increased compared to that at T2,while the MEP amplitude of patients in the P group was significantly decreased compared to that at T2,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the total incidence of postoperative complications between the two groups(P>0.05).Conclusion As a general anesthesia maintenance drug,remazolam can achieve satisfactory anesthesia effects for CEA,with more stable intraoperative hemodynamics,and less impact on ScO2 and evoked potential monitoring during carotid artery occlusion compared to propofol,resulting in higher safety.

Objective To explore the impacts and fundamental mechanisms of the PU.1 inhibitor DB2313 on the immune function in MRL/lpr mice.Methods A total of thirty MRL/lpr lupus mice were randomly distributed into three separate groups:the model control group,the PU.1 inhibitor DB2313 treatment group(administered at a dose of 17 mg/kg),and the positive drug control Telitacicept(TACI-Ig)group(administered at a dose of 7.5 mg/kg).Furthermore,a group of ten BALB/c mice were assigned as the normal group.The DB2313 administration group was treated with intraperitoneal injections of the drug on three occasions per week,while the TACI-Ig group received subcutaneous injections every second day;both treatment protocols were maintained for a duration of five weeks.Both the control group and the model group were administered intraperitoneal injections of a volume of sa-line that was equivalent across groups.After the drug was given,mice were sacrificed by dislocation after orbital vein blood collection.The thymus and spleen were aseptically excised,individually weighed,and subsequently uti-lized to compute the thymus index and spleen index.The relative distribution of T lymphocyte subsets within the spleen was ascertained through flow cytometry.Serum concentrations of anti-nuclear antibodies(ANA)and anti-double-stranded DNA antibodies were quantified using an enzyme-linked immunosorbent assay(ELISA).The lev-els of inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)were meas-ured by CBA method.Hematoxylin and eosin(HE)staining was employed to examine pathological alterations in the spleen.The expression of PU.1 and IL-9 in spleen tissue was detected using immunohistochemistry.Addition-ally,the expression level of PU.1 protein in the spleen tissue was ascertained through Western blot analysis.Re-sults The administration of DB2313 significantly ameliorated spleen lesions in MRL/lpr mice and decreased the levels of anti-ds-DNA,ANA,TNF-α,IL-6,and IFN-γ.It also reduced the proportion of total T cells,TFH cells,Th17 cells,and Th9 cells in the mouse spleen,while increasing the proportion of Treg cells.Furthermore,it low-ered the level of PU.1 protein in the spleen.Immunohistochemistry results demonstrated that DB2313 treatment sig-nificantly diminished the expression of PU.1 and IL-9 in spleen tissue.Conclusion The PU.1 inhibitor DB2313 can improve spleen lesions in MRL/lpr mice and slow the progression of the disease,and its mechanism is related to the regulation of immune cell functions.

Objective : To explore the impacts and fundamental mechanisms of the PU. 1 inhibitor DB2313 on the immune function in MRL/lpr mice. Methods: A total of thirty MRL/lpr lupus mice were randomly distributed into three separate groups : the model control group , the PU. 1 inhibitor DB2313 treatment group ( administered at a dose of 17 mg/kg) , and the positive drug control Telitacicept (TACI_Ig) group (administered at a dose of 7. 5 mg/ kg) . Furthermore , a group of ten BALB/c mice were assigned as the normal group. The DB2313 administration group was treated with intraperitoneal injections of the drug on three occasions per week , while the TACI_Ig group received subcutaneous injections every second day; both treatment protocols were maintained for a duration of five weeks. Both the control group and the model group were administered intraperitoneal injections of a volume of saline that was equivalent across groups. After the drug was given , mice were sacrificed by dislocation after orbital vein blood collection. The thymus and spleen were aseptically excised , individually weighed , and subsequently utilized to compute the thymus index and spleen index. The relative distribution of T lymphocyte subsets within the spleen was ascertained through flow cytometry. Serum concentrations of anti_nuclear antibodies ( ANA) and antidouble_stranded DNA antibodies were quantified using an enzyme_linked immunosorbent assay (ELISA) . The levels of inflammatory factors interleukin_6 (IL_6) , tumor necrosis factor_α (TNF_α) , interferon_γ(IFN_γ) were meas ured by CBA method. Hematoxylin and eosin ( HE) staining was employed to examine pathological alterations in the spleen. The expression of PU. 1 and IL_9 in spleen tissue was detected using immunohistochemistry. Additionally , the expression level of PU. 1 protein in the spleen tissue was ascertained through Western blot analysis. Results: The administration of DB2313 significantly ameliorated spleen lesions in MRL/lpr mice and decreased the levels of anti_ds_DNA , ANA , TNF_α , IL_6 , and IFN_γ . It also reduced the proportion of total T cells , TFH cells , Th17 cells , and Th9 cells in the mouse spleen , while increasing the proportion of Treg cells. Furthermore , it lowered the level of PU. 1 protein in the spleen. Immunohistochemistry results demonstrated that DB2313 treatment significantly diminished the expression of PU. 1 and IL_9 in spleen tissue. Conclusion The PU. 1 inhibitor DB2313 can improve spleen lesions in MRL/lpr mice and slow the progression of the disease , and its mechanism is related to the regulation of immune cell functions.

Objective : To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs. Methods: Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results: Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased. Conclusion Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.