Objective To investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells(hUCMSCs)in modulating the cGAS-STING-NF-κB signaling pathway in chronic intermittent hypoxia(CIH)mice.Methods Twenty-four C57BL/6 mice were divided into the control group,the model group,the hUCMSCs group and the hUCMSCs+STING agonist(DMXAA)group,with 6 mice in each group.Except for the control group,the other groups were exposed to hypoxic conditions for 8 hours daily for a total of 8 weeks to establish the CIH mouse model.After 8 weeks,mice were anesthetized for cardiac blood collection followed by euthanasia and lung tissue collection.Serum levels of IL-6,TNF-α,IL-1β and IL-17A were measured by ELISA.Pulmonary inflammatory infiltration and collagen deposition were assessed by HE and Masson staining.E-Cadherin and α-SMA expression levels were evaluated by immunohistochemistry.Expression levels of cGAS,STING and NF-κB mRNA were detected by RT-qPCR,while protein expression levels of E-Cadherin,N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were analyzed by Western blot assay.Results Compared with the control group,levels of IL-6,IL-1β,TNF-α and IL-17A increased in the model group,inflammation and fibrosis scores increased,mRNA expression levels of cGAS,STING and NF-κB increased,and protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB increased.In contrast,E-Cadherin protein expression was significantly decreased(P＜0.05).Compared with the model group,IL-6,IL-1β,TNF-α and IL-17A decreased in the hUCMSCs group,mRNA expression levels of cGAS,STING and NF-κB were decreased,protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were also decreased.Meanwhile,E-Cadherin protein expression was significantly increased(P＜0.05).STING activator DMXAA reversed the protective effects of hUCMSCs in CIH mice(P＜0.05).Conclusion Intravenous administration of hUCMSCs alleviates pulmonary inflammatory infiltration and epithelial-mesenchymal transition in mouse model of intermittent hypoxia,which may be related to the down-regulation of the cGAS-STING-NF-κBsignaling pathway.

Objective To explore the correlation between thyroid hormone(TH)sensitivity and diabetic retinopathy(DR)in type 2 diabetes mellitus(T2DM)patients with normal thyroid function.Methods A total of 776 patients with T2DM and normal thyroid function who were hospitalized in the Department of Endocrinology and Metabolism in Heze Mudan People's Hospital between July 2023 and January 2025 were enrolled in this study.They were divided into the simple T2DM group(n=456)and the DR group(n=320)based on the presence or absence of DR.The general data,biochemical indicators,thyroid feedback quartile index(TFQI),parameterized TFQI(PTFQI),thyroid stimulating hormone index(TSHI),thyroid resistance index(TT4RI),free triiodothyronine/free thyroxine(FT3/FT4),etc.were compared between the two groups.Logistic regression analysis was used to explore the influencing factors of DR.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of thyroid function-related parameters for DR.Results The DR group had higher age,the proportion of hypertension,the proportion of coronary heart disease,DM duration,the proportion of smoking,hemoglobin A1c(HbA1c),triglycerides,thyroid stimulating hormone(TSH),TFQI,PTFQI,TSHI,and TT4RI(P<0.05),while the proportion of male,fasting C-peptide,and FT4 were lower compared with the T2DM group(P<0.05).Logistic regression analysis revealed that age,DM duration,the proportion of smoking,TFQI,PTFQI,TT4RI,TSHI,and HbA1c were the influencing factors for the occurrence of DR in patients with T2DM.After adjusting for confounding factors,the risk of DR increased for each indicator in the Q4 groups compared with the Q1 quartile groups of TFQI,PTFQI,TT4RI,and TSHI respectively(OR 1.954,1.080,1.853,2.028,95%CI 1.039～3.676,1.035～1.127,1.003～3.426,1.090～3.775).The ROC curve analysis showed that the areas under the curve in predicting the occurrence of DR in patients with T2DM were 0.648,0.609,0.590,and 0.580 for TFQI,PTFQI,TT4RI,and TSHI respectively,and the sensitivities were 0.385,0.647,0.465,and 0.601 respectively,while the specificities were 0.615,0.578,0.258,and 0.541 respectively.Conclusions Central resistance to TH is associated with an elevated risk of DR in euthyroid patients with T2DM.

Objective To investigate the association between novel evaluation indicators of IR and LEAD in patients with T2DM.Methods A total of 1,164 T2DM patients hospitalized in the Department of Endocrinology and Metabolism of Heze Mudan People's Hospital from January 2022 to April 2025 were enrolled.They were divided into the non-LEAD group(694 cases)and the LEAD group(470 cases)according to the presence of LEAD.General data and biochemical indicators were collected,and the triglyceride-glucose index(TyG),triglyceride-glucose-body mass index(TyG-BMI),estimated glucose disposal rate(eGDR),triglyceride-to-high-density lipo-protein cholesterol ratio(TG/HDL-C),and Metabolic Syndrome Insulin Resistance index(METS-IR)were calcu-lated.Logistic regression analysis was performed to analyze the influencing factors for the development of LEAD in T2DM patients,as well as the correlation between novel IR assessment indices grouped by different quartiles and the risk of LEAD onset.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of these indicators for LEAD.Results Compared with non-LEAD group,the LEAD group had significantly higher TyG,TyG-BMI,TG/HDL-C,and METS-IR,but lower eGDR(all P<0.05).Logistic regression analysis showed that TyG,TyG-BMI,and METS-IR were identified as risk factors for the development of LEAD in patients with T2DM,while eGDR was a protective factor against it.After adjusting for confounders,compared with the Q1 group,the Q4 groups of TyG(OR=3.647,95%CI:1.082～7.972,P<0.001),TyG-BMI(OR=3.027,95%CI:1.275～9.753,P<0.001),and METS-IR(OR=4.032,95%CI:1.242～12.385,P<0.001)had a significantly increased LEAD risk,while the Q4 group of eGDR had a significantly decreased risk(OR=0.225,95%CI:0.118～0.429,P<0.001).ROC curve analysis showed that METS-IR,TyG,TyG-BMI,and eGDR all exhibit predictive value for LEAD,with areas under the curve being 0.823,0.758,0.773,and 0.737,respectively.Subgroup analysis indicated that METS-IR was more strongly correlated with LEAD in subgroups of age≥60 years,disease duration≥5 years,HbA?C≥7.0%,smoking history,and hypertension.Conclusion Elevated levels of TyG,TyG-BMI,and METS-IR,along with decreased levels of eGDR,are associated with an increased risk of LEAD onset in patients with T2DM.METS-IR exhibits high predictive efficacy for the development of LEAD in T2DM patients and may serve as a tool for its screening and risk assessment.

Objective:To systematically integrate the work experience of medical and nursing staff in the remote home palliative care model, so as to provide a reference for improving remote home palliative care services.Methods:Qualitative studies on medical and nursing staff providing remote home palliative care were electronically searched in PubMed, Web of Science, Embase, ProQuest, CINAHL, PsycINFO, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc. The search period was from database establishment to April 30, 2024. Literature quality evaluation was conducted using the Joanna Briggs Institute Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. The aggregative integration method was used to synthesize the findings.Results:Researchers repeatedly read, analyzed, and interpreted the 17 included literature, extracting 56 themes and summarizing eight new categories, and further synthesized three integrated results, namely, remote home palliative care provided patients with comprehensive physical, psychological, and mental care, as well as guidance and support for family members; remote home care helped to achieve full coverage of palliative care services; equipment limitations, information security risks, and incomplete processes restricted the development of remote palliative care.Conclusions:Remote home palliative care has improved patient care and family support capabilities, expanded service coverage, and promoted interdisciplinary collaboration. However, there are still issues such as equipment limitations, information security risks, and incomplete processes. Optimizing processes, improving safety mechanisms, and strengthening collaboration platforms will contribute to sustainable development.

Objective:To investigate the current status of research in gene therapy for retinitis pigmentosa (RP) from 2005 to 2024.Methods:The literature related to gene therapy for RP included in the Web of Science Core Collection dataset from January 1, 2005 to September 15, 2024 was retrieved and screened. The bibliometrix package of R software was used to analyze the annual trend of the number of publications, citation frequency, distribution of countries/regions of the literature, and distribution of journals containing the articles. CiteSpace software was used to perform keyword clustering analysis and the keywords bursts analysis.Results:A total of 209 articles were included. There was an overall fluctuating upward trend of annual publications from 2005 to 2024, with the highest number of publications in 2023 at 26 (12.4%, 26/209), and the lowest number of publications in 2006 at 2 (0.9%, 2/209). There was an overall increasing trend in the frequency of citations to relevant literature. Corresponding authors from the United States had the highest total number of publications with 98 (46.9%, 98/209). Among authors, Hauswirth from the University of Florida, USA, had the most with 25 (12.0%, 25/209). Among institutions, Columbia University, USA, had the most with 55 (26.3%, 55/209). Among journals, Mol Ther had the most with 25 (12.0%, 25/209), and it had the highest 2023 impact factor of 12.1. Keyword clustering analysis yielded eight valid clusters, namely #0 P23H, #1 AAV, #2 PDE6B,#3 CRB1, #4 RPGR, #5 antisense oligonucleotide, #6 NR2E3, and #7 NRL, which intersected with each other with good continuity. The keywords bursts analysis showed that the keyword with the longest emergence time was RNAi, followed by PDE and PDE6. USH2A, CRB1, CRISPR Cas9, base editing, and ORF15 were keywords that emerged in recent years and were continuously studied. Conclusions:RP gene therapy research literature has shown an increasing trend from 2005 to 2024, with the highest number of publications from research organizations and scholars in the United States. Currently, studies focus on RHO, PDE6B, CRB1, RPGR, NR2E3, and NRL gene. In recent years, there has been a gradual increase in studies on USH2A, CRB1 genes, and the RPGR ORF15 region. CRISPR Cas9 and base editing gene therapy strategies are being developed.

Objective To investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells(hUCMSCs)in modulating the cGAS-STING-NF-κB signaling pathway in chronic intermittent hypoxia(CIH)mice.Methods Twenty-four C57BL/6 mice were divided into the control group,the model group,the hUCMSCs group and the hUCMSCs+STING agonist(DMXAA)group,with 6 mice in each group.Except for the control group,the other groups were exposed to hypoxic conditions for 8 hours daily for a total of 8 weeks to establish the CIH mouse model.After 8 weeks,mice were anesthetized for cardiac blood collection followed by euthanasia and lung tissue collection.Serum levels of IL-6,TNF-α,IL-1β and IL-17A were measured by ELISA.Pulmonary inflammatory infiltration and collagen deposition were assessed by HE and Masson staining.E-Cadherin and α-SMA expression levels were evaluated by immunohistochemistry.Expression levels of cGAS,STING and NF-κB mRNA were detected by RT-qPCR,while protein expression levels of E-Cadherin,N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were analyzed by Western blot assay.Results Compared with the control group,levels of IL-6,IL-1β,TNF-α and IL-17A increased in the model group,inflammation and fibrosis scores increased,mRNA expression levels of cGAS,STING and NF-κB increased,and protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB increased.In contrast,E-Cadherin protein expression was significantly decreased(P＜0.05).Compared with the model group,IL-6,IL-1β,TNF-α and IL-17A decreased in the hUCMSCs group,mRNA expression levels of cGAS,STING and NF-κB were decreased,protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were also decreased.Meanwhile,E-Cadherin protein expression was significantly increased(P＜0.05).STING activator DMXAA reversed the protective effects of hUCMSCs in CIH mice(P＜0.05).Conclusion Intravenous administration of hUCMSCs alleviates pulmonary inflammatory infiltration and epithelial-mesenchymal transition in mouse model of intermittent hypoxia,which may be related to the down-regulation of the cGAS-STING-NF-κBsignaling pathway.

Objective:To develop a 5-year mortality risk prediction model for patients with small cell neuroendocrine carcinoma of the cervix(SCNEC).Methods:Based on the Surveillance,Epidemiology,and End Results(SEER)database and R software version 4.3.3,variables were screened via Lasso regression,followed by multivariable logistic regression and stepwise regression to develop a 5-year mortality risk prediction model for SCNEC patients.The Akaike Information Criterion(AIC),C-index,receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,and calibration curve were employed to evaluate the model.Results:Age,M stage,surgical status,and lymph node metastasis were ultimately selected as variables to construct the 5-year mortality risk prediction model for SCNEC patients.The model demonstrated superior predictive performance compared to FIGO staging(P＜0.01).The Hosmer-Lemeshow test yielded a P-value＞0.05.The C-index values for the training and validation sets were 0.808 and 0.755,respectively,with the areas under the ROC curves of 0.826 and 0.744.The calibration curves of the model fluctuated near the diagonal line,indicating good agreement between predicted and observed outcomes.The decision curve analysis demonstrated significant clinical net benefit.Results showed that higher mortality risk was associated with advanced age,M1 status,lymph node metastasis,and lack of surgical opportunity.Conclusions:The model exhibits good discriminatory power and accuracy,providing significant benefits to patients.Enhanced management should be implemented for patients with advanced age,distant metastasis,lymph node metastasis,or ineligibility for surgery.Lymph node metastasis is an independent risk factor for 5-year mortality in patients with SCNEC.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

Objective:To systematically integrate the work experience of medical and nursing staff in the remote home palliative care model, so as to provide a reference for improving remote home palliative care services.Methods:Qualitative studies on medical and nursing staff providing remote home palliative care were electronically searched in PubMed, Web of Science, Embase, ProQuest, CINAHL, PsycINFO, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc. The search period was from database establishment to April 30, 2024. Literature quality evaluation was conducted using the Joanna Briggs Institute Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. The aggregative integration method was used to synthesize the findings.Results:Researchers repeatedly read, analyzed, and interpreted the 17 included literature, extracting 56 themes and summarizing eight new categories, and further synthesized three integrated results, namely, remote home palliative care provided patients with comprehensive physical, psychological, and mental care, as well as guidance and support for family members; remote home care helped to achieve full coverage of palliative care services; equipment limitations, information security risks, and incomplete processes restricted the development of remote palliative care.Conclusions:Remote home palliative care has improved patient care and family support capabilities, expanded service coverage, and promoted interdisciplinary collaboration. However, there are still issues such as equipment limitations, information security risks, and incomplete processes. Optimizing processes, improving safety mechanisms, and strengthening collaboration platforms will contribute to sustainable development.

Objective To explore the correlation between thyroid hormone(TH)sensitivity and diabetic retinopathy(DR)in type 2 diabetes mellitus(T2DM)patients with normal thyroid function.Methods A total of 776 patients with T2DM and normal thyroid function who were hospitalized in the Department of Endocrinology and Metabolism in Heze Mudan People's Hospital between July 2023 and January 2025 were enrolled in this study.They were divided into the simple T2DM group(n=456)and the DR group(n=320)based on the presence or absence of DR.The general data,biochemical indicators,thyroid feedback quartile index(TFQI),parameterized TFQI(PTFQI),thyroid stimulating hormone index(TSHI),thyroid resistance index(TT4RI),free triiodothyronine/free thyroxine(FT3/FT4),etc.were compared between the two groups.Logistic regression analysis was used to explore the influencing factors of DR.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of thyroid function-related parameters for DR.Results The DR group had higher age,the proportion of hypertension,the proportion of coronary heart disease,DM duration,the proportion of smoking,hemoglobin A1c(HbA1c),triglycerides,thyroid stimulating hormone(TSH),TFQI,PTFQI,TSHI,and TT4RI(P<0.05),while the proportion of male,fasting C-peptide,and FT4 were lower compared with the T2DM group(P<0.05).Logistic regression analysis revealed that age,DM duration,the proportion of smoking,TFQI,PTFQI,TT4RI,TSHI,and HbA1c were the influencing factors for the occurrence of DR in patients with T2DM.After adjusting for confounding factors,the risk of DR increased for each indicator in the Q4 groups compared with the Q1 quartile groups of TFQI,PTFQI,TT4RI,and TSHI respectively(OR 1.954,1.080,1.853,2.028,95%CI 1.039～3.676,1.035～1.127,1.003～3.426,1.090～3.775).The ROC curve analysis showed that the areas under the curve in predicting the occurrence of DR in patients with T2DM were 0.648,0.609,0.590,and 0.580 for TFQI,PTFQI,TT4RI,and TSHI respectively,and the sensitivities were 0.385,0.647,0.465,and 0.601 respectively,while the specificities were 0.615,0.578,0.258,and 0.541 respectively.Conclusions Central resistance to TH is associated with an elevated risk of DR in euthyroid patients with T2DM.