AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides

Objective To investigate the effect of resveratrol on the proliferation,apoptosis,and migration of breast cancer cells and its mechanism and correlation with immune cell infiltration.Methods The network pharmacology and bioinformatics(GEPIA and KM-PLOT databases)were used to predict the target genes of breast cancer regulated by resveratrol,and their expression levels in breast cancer and correlations with immune cell infiltration were verified.The effects of resveratrol on the proliferation,cell cycle and apopto-sis,and migration of breast cancer cells were determined by the CCK-8 assay,flow cytometry,and cell scratch test,respectively.The mRNA expression levels of related target genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Pearson correlation analysis was used to analyze the correlations of the expression levels of related genes with immune cell infiltration.Results The expression levels of TP53 and VEGFA genes in breast cancer tissues were significantly higher than those in normal tissues(Z=-4.181 and-8.763,P＜0.05).In the GEPIA database,the expression level of CDKN1A gene in breast cancer tis-sues was significantly higher than that in normal tissues(Z=-2.135,P＜0.05).In the KMPLOT database,the expression level of HIF1α gene in breast cancer tissues was significantly higher than that in normal tissues(Z=-2.269,P＜0.05).Pearson correlation a-nalysis showed that the expression level of TP53 gene was positively correlated with B cell infiltration(partial.cor=0.102,P＜0.01).The expression level of HIF-1α was positively correlated with the infiltration of CD8+T cells,CD4+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.39,0.159,0.284,0.325,and 0.294,P＜0.01).The expression level of VEGFA gene was positive-ly correlated with neutrophil infiltration(partial.cor=0.141,P＜0.01).The expression level of CDKN1A gene was positively correlated with the infiltration of CD8+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.081,0.209,0.11,and 0.09,P＜0.01).Resveratrol could inhibit the proliferation of breast cancer cells,and the IC50 and IC25 values of breast cancer cells were 150 μmol/L and 50 μmol/L,respectively,after 48 hours of treatment with resveratrol.In addition,resveratrol could also arrest breast cancer cells in G1 phase,induce their apoptosis,and inhibit their migration.After treating breast cancer cells with resveratrol for 24 hours,with the increase of resveratrol concentration from 50 μmol/L to 150 μmol/L,the mRNA expression levels of TP53 and HIF1α genes increased gradually,with a significant difference between the two groups(P＜0.05).After treating breast cancer cells with res-veratrol for 48 hours,the expression level of VEGFA mRNA was significantly decreased,and there was a significant difference between the two groups(P＜0.05).Conclusion TP53,HIF-1α,VEGFA,and CDKN1A genes are the action targets of resveratrol in breast cancer,which are mainly involved in the regulation of immune cell infiltration in breast cancer.Resveratrol inhibits the proliferation of breast cancer cells,induces cell cycle arrest and apoptosis,and inhibits cell migration by regulating the P53-HIF1α/CDKN1A-VEGFA signaling pathway.

Objective To observe the effects of Qigui Buxue Decoction combined with timed press-needle therapy on myelosuppression and cancer-related fatigue in chemotherapy patients with non-small cell lung cancer(NSCLC)of lung-spleen qi deficiency type.Methods A total of 124 NSCLC patients with lung-spleen qi deficiency type admitted to the Department of Radiotherapy and Chemotherapy at Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province from January 2022 to June 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 62 cases in each group.Both groups received platinum-based two-drug combination chemotherapy.The control group received timed press-needle therapy in addition to chemotherapy,while the observation group received Qigui Buxue Decoction in addition to the control group's treatment.The treatment course was 3 weeks,with a total of 2 courses.After 2 courses of treatment,changes in blood routine,lymphocyte subsets(CD3+,CD4+,CD8+,NK cells),CD4+/CD8+ratio,and the incidence of myelosuppression were observed.Changes in Piper Fatigue Scale and Karnofsky Performance Scale(KPS)scores before and after treatment were compared between the two groups.Results(1)After treatment,the white blood cell count in the observation group significantly improved(P＜0.05),and the observation group showed significantly better improvement in white blood cell count compared to the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the levels of CD3+,CD4+,CD4+/CD8+,and NK cells in both groups significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(3)The incidence of myelosuppression in the observation group was 58.06%(36/62),while it was 77.42%(48/62)in the control group.The incidence of myelosuppression in the observation group was significantly lower than that in the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the Piper Fatigue Scale scores,including behavioral,emotional,physical,and total scores,significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).The cognitive scores of the Piper Fatigue Scale showed slight improvement in both groups,but there was no statistically significant difference compared to before treatment(P＞0.05).(5)After treatment,the KPS scores and TCM syndrome scores significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).Conclusion Qigui Buxue Decoction combined with timed press-needle therapy can effectively improve myelosuppression,enhance immune function,and alleviate cancer-related fatigue in NSCLC patients with lung-spleen qi deficiency type after chemotherapy,thereby improving their quality of life.This approach is worthy of clinical promotion.

Objective:To improve the isolation and culture method of seasonal influenza virus in embryonated chicken eggs (ECEs), and evaluate their isolation efficiency.Methods:We randomly selected 80 positive samples of H1N1 (H1N1pdm09) and seasonal H3N2 (H3N2snl) influenza virus nucleic acid, and inoculated them into the amniotic and urinary sac cavities of 10-day-old (traditional method) and 14-day-old (improved method) ECEs respectively to adapt the virus to the ECEs (E1-E2). Both method were used to inoculate 10-day-old urinary sac amplification virus (E2-E3), and the final virus isolation positive rates of the two method were compared; using fluorescence quantitative PCR method to detect viral nucleic acids in the improved amniotic and urinary sac cultures, and evaluate the viral proliferation at different inoculation sites; we analyzed the correlation between virus content and isolation positivity rate in the original specimen based on the CT value of nucleic acid testing and the final virus isolation positivity rate using the improved method.Results:The improved method obtained 42 strains of H1N1pdm09 strain, with a positive rate of 52.5% ( χ2=38.571, P<0.01); obtained 54 strains of H3N2snl strain, with a positive rate of 67.5% ( χ2=40.921, P<0.01). Significant differences were observed in the isolation efficiency of H1N1pdm09 samples when the improved method was applied to different inoculation sites of chicken embryos ( χ2=30.476, P<0.01), and similar differences were noted for H3N2snl samples ( χ2=4.928, P=0.026). There was no significant difference in the isolation rate of different CT value intervals of the original samples ( χH1N1pdm092=10.226, χH3N2snl2=3.764, P>0.05). Conclusions:The improved method of inoculating 14-day old ECEs adapted the virus, and the final number of strains obtained was significantly higher than the traditional method of inoculating 10 day old ECEs, which can significantly improve the positive isolation rate of H1N1pdm09 and H3N2snl influenza virus in ECEs. The amniotic cavity is more sensitive to H1N1pdm09 and H3N2snl influenza viruses, which helps the virus adapt in ECEs. There was no significant difference in the sample isolation rate and total positive rate of virus isolation among different CT value ranges, and further verification is needed.

Objective To develop a task prompt card for critical care records,providing standardized guidance for nurses on record-keeping tasks,reducing record deficiencies caused by forgetfulness,and improving the quality of critical care records.Methods Relevant literature on critical care record was retrieved from the official website of the Chinese government,the official website of the National Health Commission,Wanfang Database,China National Knowledge Infrastructure(CNKI),VIP database,PubMed,Embase,Web of Science,Clinical Key for nursing,Cochrane Library database,and the International Guideline Network.The Joanna Briggs Institute(JBI)literature evaluation tool was used to evaluate the literature.Information related to the construction of critical care record task prompt cards in the literature was extracted to form the expert consultation letter for the Delphi method.According to the research topic and the requirements of the Delphi consultation letter,relevant experts were selected by purposive sampling.The consultation letters were sent to the experts,and after the letters were collected and statistically analyzed,the research team added,modified or deleted the items of the plan according to the experts'opinions and the results of data analysis.The Delphi method was conducted in multiple rounds until the experts'opinions were consistent.Results A total of 14 articles were ultimately included to form the expert consultation letter of the Delphi method.The first round of the Delphi method expert consultation letter contained 5 first-level indicators and 28 second-level indicators.The average score of the first-level indicators in the first round of expert consultation ranged from 4.78-5.00,with a coefficient of variation ranging from 0.00-0.09 and a full score ratio ranging from 77.8%-100.0%.The average score of the second-level indicators in the first round of expert consultation ranged from 3.44-4.89,with a coefficient of variation ranging from 0.00-0.44 and a full score ratio ranging from 33.3%-88.9%.According to the item retention criteria,4 second-level indicators were deleted,8 second-level indicators were modified and 1 second-level indicator was added.The average score of the first-level indicators in the second round of expert consultation ranged from 4.78-5.00,with a coefficient of variation ranging from 0.00-0.09 and a full score ratio ranging from 77.8%-100.0%.The average score of the second-level indicators in the second round of expert consultation ranged from 4.33-5.00,with a coefficient of variation ranging from 0.00-0.16 and a full score ratio ranging from 44.4%-100.0%.After two rounds of the Delphi method,the research team finalised a critical-care record task-reminder card that comprised 5 first-level and 25 second-level indicators.Conclusions The critical-care record task reminder card is an effective tool for preventing critical care nurses from forgetting due to interruption in record tasks,which can lead to errors or omissions in the record content.It can also improve the quality of nursing management.

Objective To explore the coupling mechanism between medical surge response resources and the spread of secondary risks during public health emergencies,as well as the effectiveness of relevant interventions.Methods Based on complex network theory,a dual-layer network model of medical resources and secondary events was constructed.The interactive feedback between medical resource status and secondary event risk,as well as the effects of network structure,were analyzed through MATLAB simulations,REPAST agent-based modeling,and mean-field analysis.Results Simulation and prediction results show that an increase in first-layer resource-deficient nodes significantly raises the activation rate and transmission speed of secondary events,while the clustering and spread of secondary events in the second layer,in turn,intensify resource depletion,creating a negative feedback loop.Mean-field analysis indicates a nonlinear positive correlation between the adequacy of medical resources and the likelihood of secondary events.Network structure analysis reveals that when the average node degree exceeds 8,resource allocation efficiency improves markedly.Conclusion There exists a dynamic coupling and bidirectional feedback relationship between medical resource status and secondary event risks.Enhancing the flexible allocation and responsiveness of medical resources,improving multi-sectoral collaborative monitoring and coordinated regulation,optimizing network connectivity and coordination mechanisms for resource distribution,and establishing dynamic monitoring and tiered early warning systems are key strategies for strengthening the resilience of healthcare systems and effectively containing the spread of secondary events.

Objective To explore the coupling mechanism between medical surge response resources and the spread of secondary risks during public health emergencies,as well as the effectiveness of relevant interventions.Methods Based on complex network theory,a dual-layer network model of medical resources and secondary events was constructed.The interactive feedback between medical resource status and secondary event risk,as well as the effects of network structure,were analyzed through MATLAB simulations,REPAST agent-based modeling,and mean-field analysis.Results Simulation and prediction results show that an increase in first-layer resource-deficient nodes significantly raises the activation rate and transmission speed of secondary events,while the clustering and spread of secondary events in the second layer,in turn,intensify resource depletion,creating a negative feedback loop.Mean-field analysis indicates a nonlinear positive correlation between the adequacy of medical resources and the likelihood of secondary events.Network structure analysis reveals that when the average node degree exceeds 8,resource allocation efficiency improves markedly.Conclusion There exists a dynamic coupling and bidirectional feedback relationship between medical resource status and secondary event risks.Enhancing the flexible allocation and responsiveness of medical resources,improving multi-sectoral collaborative monitoring and coordinated regulation,optimizing network connectivity and coordination mechanisms for resource distribution,and establishing dynamic monitoring and tiered early warning systems are key strategies for strengthening the resilience of healthcare systems and effectively containing the spread of secondary events.

Objective To investigate the effect of resveratrol on the proliferation,apoptosis,and migration of breast cancer cells and its mechanism and correlation with immune cell infiltration.Methods The network pharmacology and bioinformatics(GEPIA and KM-PLOT databases)were used to predict the target genes of breast cancer regulated by resveratrol,and their expression levels in breast cancer and correlations with immune cell infiltration were verified.The effects of resveratrol on the proliferation,cell cycle and apopto-sis,and migration of breast cancer cells were determined by the CCK-8 assay,flow cytometry,and cell scratch test,respectively.The mRNA expression levels of related target genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Pearson correlation analysis was used to analyze the correlations of the expression levels of related genes with immune cell infiltration.Results The expression levels of TP53 and VEGFA genes in breast cancer tissues were significantly higher than those in normal tissues(Z=-4.181 and-8.763,P＜0.05).In the GEPIA database,the expression level of CDKN1A gene in breast cancer tis-sues was significantly higher than that in normal tissues(Z=-2.135,P＜0.05).In the KMPLOT database,the expression level of HIF1α gene in breast cancer tissues was significantly higher than that in normal tissues(Z=-2.269,P＜0.05).Pearson correlation a-nalysis showed that the expression level of TP53 gene was positively correlated with B cell infiltration(partial.cor=0.102,P＜0.01).The expression level of HIF-1α was positively correlated with the infiltration of CD8+T cells,CD4+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.39,0.159,0.284,0.325,and 0.294,P＜0.01).The expression level of VEGFA gene was positive-ly correlated with neutrophil infiltration(partial.cor=0.141,P＜0.01).The expression level of CDKN1A gene was positively correlated with the infiltration of CD8+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.081,0.209,0.11,and 0.09,P＜0.01).Resveratrol could inhibit the proliferation of breast cancer cells,and the IC50 and IC25 values of breast cancer cells were 150 μmol/L and 50 μmol/L,respectively,after 48 hours of treatment with resveratrol.In addition,resveratrol could also arrest breast cancer cells in G1 phase,induce their apoptosis,and inhibit their migration.After treating breast cancer cells with resveratrol for 24 hours,with the increase of resveratrol concentration from 50 μmol/L to 150 μmol/L,the mRNA expression levels of TP53 and HIF1α genes increased gradually,with a significant difference between the two groups(P＜0.05).After treating breast cancer cells with res-veratrol for 48 hours,the expression level of VEGFA mRNA was significantly decreased,and there was a significant difference between the two groups(P＜0.05).Conclusion TP53,HIF-1α,VEGFA,and CDKN1A genes are the action targets of resveratrol in breast cancer,which are mainly involved in the regulation of immune cell infiltration in breast cancer.Resveratrol inhibits the proliferation of breast cancer cells,induces cell cycle arrest and apoptosis,and inhibits cell migration by regulating the P53-HIF1α/CDKN1A-VEGFA signaling pathway.

Objective To develop a task prompt card for critical care records,providing standardized guidance for nurses on record-keeping tasks,reducing record deficiencies caused by forgetfulness,and improving the quality of critical care records.Methods Relevant literature on critical care record was retrieved from the official website of the Chinese government,the official website of the National Health Commission,Wanfang Database,China National Knowledge Infrastructure(CNKI),VIP database,PubMed,Embase,Web of Science,Clinical Key for nursing,Cochrane Library database,and the International Guideline Network.The Joanna Briggs Institute(JBI)literature evaluation tool was used to evaluate the literature.Information related to the construction of critical care record task prompt cards in the literature was extracted to form the expert consultation letter for the Delphi method.According to the research topic and the requirements of the Delphi consultation letter,relevant experts were selected by purposive sampling.The consultation letters were sent to the experts,and after the letters were collected and statistically analyzed,the research team added,modified or deleted the items of the plan according to the experts'opinions and the results of data analysis.The Delphi method was conducted in multiple rounds until the experts'opinions were consistent.Results A total of 14 articles were ultimately included to form the expert consultation letter of the Delphi method.The first round of the Delphi method expert consultation letter contained 5 first-level indicators and 28 second-level indicators.The average score of the first-level indicators in the first round of expert consultation ranged from 4.78-5.00,with a coefficient of variation ranging from 0.00-0.09 and a full score ratio ranging from 77.8%-100.0%.The average score of the second-level indicators in the first round of expert consultation ranged from 3.44-4.89,with a coefficient of variation ranging from 0.00-0.44 and a full score ratio ranging from 33.3%-88.9%.According to the item retention criteria,4 second-level indicators were deleted,8 second-level indicators were modified and 1 second-level indicator was added.The average score of the first-level indicators in the second round of expert consultation ranged from 4.78-5.00,with a coefficient of variation ranging from 0.00-0.09 and a full score ratio ranging from 77.8%-100.0%.The average score of the second-level indicators in the second round of expert consultation ranged from 4.33-5.00,with a coefficient of variation ranging from 0.00-0.16 and a full score ratio ranging from 44.4%-100.0%.After two rounds of the Delphi method,the research team finalised a critical-care record task-reminder card that comprised 5 first-level and 25 second-level indicators.Conclusions The critical-care record task reminder card is an effective tool for preventing critical care nurses from forgetting due to interruption in record tasks,which can lead to errors or omissions in the record content.It can also improve the quality of nursing management.