Objective:To investigate the role of telomere length in the causal effects of immune-mediated diseases on liver fibrosis.Methods:Genome-wide association study (GWAS) data were extracted from open GWAS (https: //gwas.mrcieu.ac.uk) for a two-sample Mendelian randomization (MR) analysis. Five immune-mediated autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease) individually and collectively were included as exposure factors, telomere length as a mediator, and liver fibrosis as the outcome. The Wald ratio and inverse variance weighted (IVW) methods were performed to assess causal effects. The MR-Egger intercept test was adopted to evaluate the level of horizontal pleiotropy. Multivariable MR was employed to quantify the proportion of the effect of immune-mediated diseases on liver fibrosis mediated by telomere length. And sensitivity analyses were performed to assess the robustness of the results.Results:The results of IVW analysis revealed that the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease were causally related to the high risk of liver fibrosis, and the OR were 1.63 (95% confidence intervals (95% CI): 1.33 to 2.10), 1.28 (95% CI: 1.14 to 1.43), 1.34 (95% CI: 1.02 to 1.74), 1.36 (95% CI: 1.27 to 1.47), 1.37 (95% CI: 1.23 to 1.52), and 1.52 (95% CI: 1.15 to 2.01), respectively ( P<0.001, <0.001, =0.032, <0.001, <0.001, =0.003). Horizontal pleiotropy was detected in the association between Crohn′s disease and liver fibrosis (MR-Egger intercept test, P=0.025).The results of multivariable MR indicated that telomere length acted as a mediating factor in the causal relationship between liver fibrosis and the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cholangitis ( OR=2.24, 95% CI: 1.41 to 3.56; OR=1.78, 95% CI: 1.03 to 3.06; OR=2.11, 95% CI: 1.31 to 3.40; OR=2.01, 95% CI: 1.06 to 3.80; P<0.001, =0.038, =0.002, =0.032, respectively ). Conclusion:The causal effects of the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis on liver fibrosis are mediated by telomere length.

Objective:To investigate the relationship between serum apolipoprotein A1 (ApoA1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), proinflammatory protein S100A9 (S100A9) and prognosis in patients with myelodysplastic syndrome (MDS).Methods:122 MDS patients visited Qinhuangdao First Hospital from January 2020 to January 2021 were selected as the research objects. After three years of follow up, patients were divided into survival group and death group based on survival status. The differences in ApoA1, CTLA-4, and S100A9 between the death group and the survival group were compared. Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Univariate and multivariate Logistic regression analysis were used to analyze factors related to death. Results:There was no lost to follow up patients after three years of follow up. Among those 122 patients, 92 survived and 30 died. The ratio of bone marrow primitive cells>5%, IPSS-R score, serum CTLA-4, and S100A9 levels in the survival group were (2.89±2.15), (3.13±1.95) points, (5.12±1.59) μg/L, (1643.98±429.65)ng/L, respectively, lower than (5.67±3.76), (5.12±2.36) points, (28.67±6.98) μg/L, (2895.64±553.62) ng/L in the death group ( t=5.03, 4.60, 30.27, 12.87, respectively, all P<0.01). The relative high-risk ratio of IPSS-R stratification in the survival group was 63.04%,(58/92) which was lower than the 86.67%(26/30) in the death group ( χ2=5.89, P=0.015). The absolute values of hemoglobin, lymphocytes and neutrophils, and values of platelets and ApoA1 in the survival group were(86.74±12.69)g/L, (1.41±0.23)×10 9/L, (1.42±0.55)×10 9/L, (59.98±21.37)×10 9/L, (1.09±0.40) g/L respectively, which were higher than (65.58±10.89)g/L, (0.68±0.17)×10 9/L, (0.96±0.31)×10 9/L, (42.85±20.95)×10 9/L, (0.91±0.36)g/L in the death group ( t=8.20, 16.00, 4.35, 7.90, 2.19; respectively, P<0.001, <0.001, <0.001, <0.001, =0.030). Multivariate Logistic regression model analysis showed that, bone marrow blasts cells>5% ( OR=1.732, 95% CI: 1.188~2.523, P=0.004), relatively high IPSS-R stratification ( OR=1.815, 95% CI: 1.332~2.474, P<0.001), high IPSS-R score ( OR=1.785, 95% CI: 1.259~2.529, P=0.001), high CTLA-4 level ( OR=2.156, 95% CI: 1.482~3.134, P<0.001) and high S100A9 level ( OR=1.787, 95% CI: 1.218~2.625, P=0.003) were risk factors for poor prognosis in MDS patients, while high ApoA1 level ( OR=0.785, 95% CI: 0.658~0.937, P=0.007) was a protective factor ( P<0.05). Conclusion:The decrease in ApoA1 levels and the increase in CTLA-4 and S100A9 levels in MDS patients are associated with poor prognosis.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective: To improve the efficiency and standardization of preoperative anemia diagnosis and treatment by establishing a systematic intelligent management platform for preoperative anemia. Methods: A multidisciplinary collaborative model was adopted to develop a preoperative anemia management system that integrates intelligent early warning, standardized treatment pathways, and quality control. The system utilizes natural language processing technology to automatically capture laboratory data and establish evidence-based medical decision support functions. A pre-post study design was employed to compare changes in preoperative anemia screening rates, preoperative anemia intervention rates, reasonable use of iron supplements, and perioperative red blood cell transfusion rates before and after system implementation. Results: After system implementation, the standardization of anemia diagnosis and treatment significantly improved: 1) Screening effectiveness: The anemia screening rate increased to 50.00% (an increase of 27.24%); 2) Intervention effectiveness: The anemia treatment rate rose to 56.30% (an increase of 14.02%); 3) Treatment standardization: The reasonable use rate of iron supplements increased to 55.33% (an increase of 21.02%); the red blood cell transfusion rate decreased to 18.29% (a decrease of 4.07%), and the amount of red blood cell transfusions was reduced by 291 units. Conclusion: This system achieves full-process management of preoperative anemia through information technology, significantly enhancing the standardization of diagnosis and treatment as well as intervention effectiveness, providing an effective solution for perioperative anemia management.

Objective:To detect the expression level and clinical significance of centromere protein I (CENPI) in hepatocellular carcinoma (HCC) and to preliminarily explore the effects of CENPI on the biological behavior of liver cancer cells and its possible molecular mechanisms. Methods:The TCGA database, real-time fluorescent quantitative polymerase chain reaction, Western blot, and immunohistochemical staining experiments were used to analyze and detect the expression differences of CENPI in liver cancer and adjacent tissues. The correlation between CENPI expression levels and clinical pathological features were analyzed in combination with clinical data from HCC patients. The value of CENPI in the diagnosis and prognosis assessment of HCC was explored by plotting receiver operating characteristic curves and Kaplan-Meier survival curves. Furthermore, we investigated the impact of CENPI overexpression on the migration and healing capabilities of liver cancer cells using Transwell and wound healing experiments. Finally, the effects of CENPI on the epithelial-mesenchymal transition process in liver cancer cells and the potential molecular mechanisms were explored using Western blot. Comparisons between two groups were analyzed using t-tests, and comparisons among multiple groups were analyzed using one-way ANOVA. The expression of CENPI and its correlation with clinical pathological features were analyzed using the χ2 test. Results:The TCGA database analysis showed that the expression level of CENPI was significantly higher in liver cancer tissues than adjacent tissues, which was further validated by real-time fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining experiments. Combined clinical data analysis from HCC patients demonstrated that high expression of CENPI was positively correlated with the degree of tumor malignancy, T stage, and disease prognosis. The Kaplan-Meier survival curve indicated that the 5-year survival rate was significantly lower in patients with high CENPI expression compared to those with low expression. The results of the receiver operating characteristic curve further indicated that the expression level of CENPI had accurately predicted the prognosis of liver cancer patients (area under the curve=0.962). Transwell and wound healing experiment results indicated that overexpressing CENPI in Hep3B and Huh7 cells significantly increased cell migration numbers and healing rates. Further research results showed that overexpressing CENPI significantly upregulated the expression of mesenchymal cell-related marker genes: N-cadherin, Vimentin, and Snail protein, while the expression of the epithelial cell-related marker gene E-cadherin was significantly reduced. The mechanistic study revealed that when CENPI was overexpressed, the MEK and ERK phosphorylation levels and the expression of RAS protein were significantly increased compared to the control group, and the difference was statistically significant. Conclusion:The high expression of CENPI in the tissues of HCC patients is associated with poor prognosis, potentially promoting the migration of liver cancer cells and the epithelial-mesenchymal transition process by activating the RAS/MEK/ERK signaling pathway axis, suggesting that the CENPI gene may be a promising target for HCC treatment.

AIM:To investigate the modulatory effects of electroacupuncture(EA)on spinal cord neurons au-tophagy in rats with bone cancer pain.METHODS:(1)Verification of autophagy-related protein expression at different time points in a bone cancer pain model:a total of 56 female Sprague-Dawley(SD)rats were randomly divided into a sham-operated(sham)group and a model group.The model group was further subdivided into 6 subgroups corresponding to time points of 3,6,9,12,15,and 18 d,with 8 rats per subgroup.Thermal and mechanical pain thresholds,tibial bone destruction,and spinal neuron marker neuronal nuclear antigen(NeuN)co-localized with LC3B,Beclin1,and P62 were examined in rats at each designated time point.(2)Changes in spinal autophagy proteins following EA intervention:an additional 40 rats were randomly assigned to sham group,model group,EA group,sham EA(SEA)group,and autoph-agy agonist rapamycin(Rap)group,with 8 animals per group.EA was administered to the rats in EA group beginning on day 6 after modeling,the rats in SEA group received needle insertion without electrical stimulation,while those in Rap group received intraperitoneal injections of rapamycin(5 mg/kg).Thermal pain thresholds were assessed at designated in-tervals,followed by mechanical pain threshold assessments conducted on the subsequent day.Treatment continued until day 21,with rapamycin administered at the end of each intervention day.Tibial bone destruction was evaluated using he-matoxylin-eosin(HE)staining.Expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 proteins in the spinal cord were determined by Western blot and immunohistochemistry.RESULTS:(1)Compared with the Sham group,thermal and mechanical pain thresholds were significantly decreased in the model group starting from day 6(P<0.01).Rat tibial bones exhibited notable damage,with severity progressively increasing over time.Protein expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 were significantly elevated in the spinal cord at various time points(P<0.01),and these pro-teins were co-localized with spinal cord neurons.(2)Compared with the model group,mechanical and thermal pain thresholds in the EA and Rap groups gradually increased,with statistically significant differences observed from days 8 and 6 onward,respectively(P<0.01).In addition,LC3B Ⅱ/LC3B I and Beclin1 protein expression levels were signifi-cantly upregulated(P<0.01),whereas P62 expression was markedly downregulated(P<0.01).Immunohistochemical analysis demonstrated significantly enhanced positive staining for LC3B Ⅱ/LC3B I and Beclin1 and significantly decreased positive staining for P62 in the spinal cord of rats in the EA and Rap groups(P<0.05).Notably,no significant differences were observed in the SEA group(P>0.05).CONCLUSION:EA promotes spinal cord neurons autophagy in rats with bone cancer pain.The enhancement of autophagy may represent a potential mechanism underlying the analgesic effect of EA in bone cancer pain.

Objective To explore the effect of Omaha system continuity nursing on the degree of pain and quality of life in patients undergoing arthroscopic rotator cuff repair.Methods A total of 110 patients who underwent arthroscopic rotator cuff repair at the First Affiliated Hospital of Wenzhou Medical University from September 2022 to May 2023 were selected.They were divided into intervention group and control group according to the random number table method,with 55 cases in each group.Patients in control group were given conventional continuous nursing,while patients in intervention group were given Omaha system continuity nursing.Both groups of patients were intervened for 6 months.The range of motion of shoulder joint,shoulder joint function,degree of pain and quality of life of two groups of patients before and after the intervention were compared.Results After the intervention,the range of motion of shoulder joint in intervention group was significantly greater than that in control group,University of California,Los Angeles shoulder joint score and the 8-item short form health survey were significantly higher than those in control group,and numerical rating scale score of pain was significantly lower than that in control group(P＜0.05).Conclusion Omaha system continuity nursing can improve shoulder joint mobility and function,alleriate pain,and improve quality of life for patients undergoing arthroscopic rotator cuff repair surgery.

AIM:To investigate the modulatory effects of electroacupuncture(EA)on spinal cord neurons au-tophagy in rats with bone cancer pain.METHODS:(1)Verification of autophagy-related protein expression at different time points in a bone cancer pain model:a total of 56 female Sprague-Dawley(SD)rats were randomly divided into a sham-operated(sham)group and a model group.The model group was further subdivided into 6 subgroups corresponding to time points of 3,6,9,12,15,and 18 d,with 8 rats per subgroup.Thermal and mechanical pain thresholds,tibial bone destruction,and spinal neuron marker neuronal nuclear antigen(NeuN)co-localized with LC3B,Beclin1,and P62 were examined in rats at each designated time point.(2)Changes in spinal autophagy proteins following EA intervention:an additional 40 rats were randomly assigned to sham group,model group,EA group,sham EA(SEA)group,and autoph-agy agonist rapamycin(Rap)group,with 8 animals per group.EA was administered to the rats in EA group beginning on day 6 after modeling,the rats in SEA group received needle insertion without electrical stimulation,while those in Rap group received intraperitoneal injections of rapamycin(5 mg/kg).Thermal pain thresholds were assessed at designated in-tervals,followed by mechanical pain threshold assessments conducted on the subsequent day.Treatment continued until day 21,with rapamycin administered at the end of each intervention day.Tibial bone destruction was evaluated using he-matoxylin-eosin(HE)staining.Expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 proteins in the spinal cord were determined by Western blot and immunohistochemistry.RESULTS:(1)Compared with the Sham group,thermal and mechanical pain thresholds were significantly decreased in the model group starting from day 6(P<0.01).Rat tibial bones exhibited notable damage,with severity progressively increasing over time.Protein expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 were significantly elevated in the spinal cord at various time points(P<0.01),and these pro-teins were co-localized with spinal cord neurons.(2)Compared with the model group,mechanical and thermal pain thresholds in the EA and Rap groups gradually increased,with statistically significant differences observed from days 8 and 6 onward,respectively(P<0.01).In addition,LC3B Ⅱ/LC3B I and Beclin1 protein expression levels were signifi-cantly upregulated(P<0.01),whereas P62 expression was markedly downregulated(P<0.01).Immunohistochemical analysis demonstrated significantly enhanced positive staining for LC3B Ⅱ/LC3B I and Beclin1 and significantly decreased positive staining for P62 in the spinal cord of rats in the EA and Rap groups(P<0.05).Notably,no significant differences were observed in the SEA group(P>0.05).CONCLUSION:EA promotes spinal cord neurons autophagy in rats with bone cancer pain.The enhancement of autophagy may represent a potential mechanism underlying the analgesic effect of EA in bone cancer pain.

Objective To explore the effect of Omaha system continuity nursing on the degree of pain and quality of life in patients undergoing arthroscopic rotator cuff repair.Methods A total of 110 patients who underwent arthroscopic rotator cuff repair at the First Affiliated Hospital of Wenzhou Medical University from September 2022 to May 2023 were selected.They were divided into intervention group and control group according to the random number table method,with 55 cases in each group.Patients in control group were given conventional continuous nursing,while patients in intervention group were given Omaha system continuity nursing.Both groups of patients were intervened for 6 months.The range of motion of shoulder joint,shoulder joint function,degree of pain and quality of life of two groups of patients before and after the intervention were compared.Results After the intervention,the range of motion of shoulder joint in intervention group was significantly greater than that in control group,University of California,Los Angeles shoulder joint score and the 8-item short form health survey were significantly higher than those in control group,and numerical rating scale score of pain was significantly lower than that in control group(P＜0.05).Conclusion Omaha system continuity nursing can improve shoulder joint mobility and function,alleriate pain,and improve quality of life for patients undergoing arthroscopic rotator cuff repair surgery.

Objective:To investigate the relationship between serum apolipoprotein A1 (ApoA1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), proinflammatory protein S100A9 (S100A9) and prognosis in patients with myelodysplastic syndrome (MDS).Methods:122 MDS patients visited Qinhuangdao First Hospital from January 2020 to January 2021 were selected as the research objects. After three years of follow up, patients were divided into survival group and death group based on survival status. The differences in ApoA1, CTLA-4, and S100A9 between the death group and the survival group were compared. Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Univariate and multivariate Logistic regression analysis were used to analyze factors related to death. Results:There was no lost to follow up patients after three years of follow up. Among those 122 patients, 92 survived and 30 died. The ratio of bone marrow primitive cells>5%, IPSS-R score, serum CTLA-4, and S100A9 levels in the survival group were (2.89±2.15), (3.13±1.95) points, (5.12±1.59) μg/L, (1643.98±429.65)ng/L, respectively, lower than (5.67±3.76), (5.12±2.36) points, (28.67±6.98) μg/L, (2895.64±553.62) ng/L in the death group ( t=5.03, 4.60, 30.27, 12.87, respectively, all P<0.01). The relative high-risk ratio of IPSS-R stratification in the survival group was 63.04%,(58/92) which was lower than the 86.67%(26/30) in the death group ( χ2=5.89, P=0.015). The absolute values of hemoglobin, lymphocytes and neutrophils, and values of platelets and ApoA1 in the survival group were(86.74±12.69)g/L, (1.41±0.23)×10 9/L, (1.42±0.55)×10 9/L, (59.98±21.37)×10 9/L, (1.09±0.40) g/L respectively, which were higher than (65.58±10.89)g/L, (0.68±0.17)×10 9/L, (0.96±0.31)×10 9/L, (42.85±20.95)×10 9/L, (0.91±0.36)g/L in the death group ( t=8.20, 16.00, 4.35, 7.90, 2.19; respectively, P<0.001, <0.001, <0.001, <0.001, =0.030). Multivariate Logistic regression model analysis showed that, bone marrow blasts cells>5% ( OR=1.732, 95% CI: 1.188~2.523, P=0.004), relatively high IPSS-R stratification ( OR=1.815, 95% CI: 1.332~2.474, P<0.001), high IPSS-R score ( OR=1.785, 95% CI: 1.259~2.529, P=0.001), high CTLA-4 level ( OR=2.156, 95% CI: 1.482~3.134, P<0.001) and high S100A9 level ( OR=1.787, 95% CI: 1.218~2.625, P=0.003) were risk factors for poor prognosis in MDS patients, while high ApoA1 level ( OR=0.785, 95% CI: 0.658~0.937, P=0.007) was a protective factor ( P<0.05). Conclusion:The decrease in ApoA1 levels and the increase in CTLA-4 and S100A9 levels in MDS patients are associated with poor prognosis.