Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Objective:To analyze serum inflammatory factors associated with antihistamine resistance in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 88 CSU patients were enrolled from Guangzhou Dermatology Hospital from January 2022 to December 2024. All patients received antihistamine treatment according to the "Guideline for diagnosis and treatment of urticaria in China (2022) " . Based on the 7-day urticaria activity score (UAS7) after 4-week treatment, these patients were divided into an antihistamine-sensitive group and an antihistamine-resistant group. Serum levels of inflammatory factors at the initial visit were analyzed using the Olink-targeted proteomics technology. Specific biomarkers associated with antihistamine resistance were identified, and Spearman correlation analysis was carried out to analyze correlations among differentially expressed proteins. A logistic regression model was constructed based on the Olink proteomics data, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Measurement data were expressed as mean ± standard deviation or median (lower quartile, upper quartile) .Results:The 88 CSU patients aged 12 to 81 (38.78 ± 13.89) years, with the disease duration being 18 (7.00, 60.00) months. There were 32 patients in the antihistamine-sensitive group and 56 in the antihistamine-resistant group. No significant differences were found between the two groups in terms of age, disease duration, gender, or history of allergic diseases (all P > 0.05) . After 4 weeks of antihistamine treatment, the UAS7 score was significantly higher in the antihistamine-resistant group (25.00 [15.25, 31.00] points) than in the antihistamine-sensitive group (0.50 [0.00, 4.00] points; Z = -7.08, P < 0.001) . The Olink-targeted proteomics identified 5 differentially expressed proteins between the two groups: compared with the antihistamine-sensitive group, the antihistamine-resistant group showed > 2-fold higher expression of fibroblast growth factor 19 (FGF19) , interleukin-15 receptor subunit alpha (IL-15RA) , eotaxin (CCL11) , and monocyte chemoattractant protein-1 (MCP-1) ; in contrast, the expression of sulfotransferase 1A1 (ST1A1) in the antihistamine-sensitive group was 2.54 times that in the antihistamine-resistant group. Among the differentially expressed proteins, MCP-1 showed the highest specificity (1.00) for predicting antihistamine resistance, followed by CCL11 (0.97) . Correlation analysis revealed a significant positive correlation between MCP-1 and CCL11, and a significant negative correlation between IL-15RA and ST1A1. ROC curve analysis showed that MCP-1 and CCL11 had area under the curve values of 0.603 and 0.630, respectively, in predicting antihistamine resistance. Conclusion:MCP-1 and CCL11 may be potential biomarkers for predicting antihistamine resistance in CSU patients.

Objectives:To compare the biomechanical characteristics of 3D-printed titanium alloy artificial vertebral bodies(AVB)with standard,self-stabilizing,and truss structures in spinal reconstruction after total en bloc spondylectomy(TES).Methods:A finite element model of the normal spine was constructed based on the CT data of the T10-L2 segments of a healthy adult male and was subsequently validated.The defect after vertebral column resection was simulated by removing the T12 vertebra,and three types of 3D-printed titanium alloy AVBs were implanted:standard(cylindrical),self-stabilizing(with two pairs of screws at the upper and lower ends),and truss(with bilateral ring holes for screw-rod connection).A 200N axial load and a 7.5N·m torque were applied using Abaqus software to simulate flexion,extension,lateral bending,and rotation movements.The overall stiffness of the"vertebra-prosthesis-vertebra"composite structure,the stress distributions on the posterior column connecting rod,the endplate,and the fusion device were analyzed.Results:The range of motion of the T10-L2 normal spinal finite element model established in this study was consistent with previous literature reports,therefore validating the model.Stiffness analysis showed that the displacement difference among the standard,truss,and self-stabilizing AVBs under the same load was 0.1mm,with the self-stabilizing structure AVB exhibiting the smallest displacement;The truss structure had smaller displacement in left-right bending.Stress analysis results indicated that the posterior column connecting rods of the three kinds of morphological AVBs bore the maximum Von Mises stress(174.90-175.00MPa)during rotation.Compared with the standard structure,the truss structure reduced the mid-segment stress of the posterior column connecting rod by 18.5％-24.3％during flexion-extension and lateral bending.Endplate stress analysis revealed that the maximum Von Mises stress on the endplate occurred during flexion,with values of 32.54MPa,30.76MPa,and 24.37MPa for the standard,truss,and self-stabilizing structures,respectively.The self-stabilizing structure reduced endplate stress by 14％-30％compared with the other two structures.Analysis of the internal fixation system showed that the cage stress of the self-stabilizing AVB was significantly lower than that of the standard and truss structures:reduced by 57％and 61％in flexion;52％-62％and 59％-64％in lateral bending;and 61％-62％and 46％-61％in rotation,respectively.Conclusions:Compared to the standard structure,the truss structure AVB reduces the stress concentration of the posterior column connecting rod through a multi-segment stress dispersion mechanism.The self-stabilizing structure AVB enhances the stability of the prosthesis-vertebral body interface through screw fixation.

Objective:To analyze serum inflammatory factors associated with antihistamine resistance in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 88 CSU patients were enrolled from Guangzhou Dermatology Hospital from January 2022 to December 2024. All patients received antihistamine treatment according to the "Guideline for diagnosis and treatment of urticaria in China (2022) " . Based on the 7-day urticaria activity score (UAS7) after 4-week treatment, these patients were divided into an antihistamine-sensitive group and an antihistamine-resistant group. Serum levels of inflammatory factors at the initial visit were analyzed using the Olink-targeted proteomics technology. Specific biomarkers associated with antihistamine resistance were identified, and Spearman correlation analysis was carried out to analyze correlations among differentially expressed proteins. A logistic regression model was constructed based on the Olink proteomics data, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Measurement data were expressed as mean ± standard deviation or median (lower quartile, upper quartile) .Results:The 88 CSU patients aged 12 to 81 (38.78 ± 13.89) years, with the disease duration being 18 (7.00, 60.00) months. There were 32 patients in the antihistamine-sensitive group and 56 in the antihistamine-resistant group. No significant differences were found between the two groups in terms of age, disease duration, gender, or history of allergic diseases (all P > 0.05) . After 4 weeks of antihistamine treatment, the UAS7 score was significantly higher in the antihistamine-resistant group (25.00 [15.25, 31.00] points) than in the antihistamine-sensitive group (0.50 [0.00, 4.00] points; Z = -7.08, P < 0.001) . The Olink-targeted proteomics identified 5 differentially expressed proteins between the two groups: compared with the antihistamine-sensitive group, the antihistamine-resistant group showed > 2-fold higher expression of fibroblast growth factor 19 (FGF19) , interleukin-15 receptor subunit alpha (IL-15RA) , eotaxin (CCL11) , and monocyte chemoattractant protein-1 (MCP-1) ; in contrast, the expression of sulfotransferase 1A1 (ST1A1) in the antihistamine-sensitive group was 2.54 times that in the antihistamine-resistant group. Among the differentially expressed proteins, MCP-1 showed the highest specificity (1.00) for predicting antihistamine resistance, followed by CCL11 (0.97) . Correlation analysis revealed a significant positive correlation between MCP-1 and CCL11, and a significant negative correlation between IL-15RA and ST1A1. ROC curve analysis showed that MCP-1 and CCL11 had area under the curve values of 0.603 and 0.630, respectively, in predicting antihistamine resistance. Conclusion:MCP-1 and CCL11 may be potential biomarkers for predicting antihistamine resistance in CSU patients.

Objectives:To compare the biomechanical characteristics of 3D-printed titanium alloy artificial vertebral bodies(AVB)with standard,self-stabilizing,and truss structures in spinal reconstruction after total en bloc spondylectomy(TES).Methods:A finite element model of the normal spine was constructed based on the CT data of the T10-L2 segments of a healthy adult male and was subsequently validated.The defect after vertebral column resection was simulated by removing the T12 vertebra,and three types of 3D-printed titanium alloy AVBs were implanted:standard(cylindrical),self-stabilizing(with two pairs of screws at the upper and lower ends),and truss(with bilateral ring holes for screw-rod connection).A 200N axial load and a 7.5N·m torque were applied using Abaqus software to simulate flexion,extension,lateral bending,and rotation movements.The overall stiffness of the"vertebra-prosthesis-vertebra"composite structure,the stress distributions on the posterior column connecting rod,the endplate,and the fusion device were analyzed.Results:The range of motion of the T10-L2 normal spinal finite element model established in this study was consistent with previous literature reports,therefore validating the model.Stiffness analysis showed that the displacement difference among the standard,truss,and self-stabilizing AVBs under the same load was 0.1mm,with the self-stabilizing structure AVB exhibiting the smallest displacement;The truss structure had smaller displacement in left-right bending.Stress analysis results indicated that the posterior column connecting rods of the three kinds of morphological AVBs bore the maximum Von Mises stress(174.90-175.00MPa)during rotation.Compared with the standard structure,the truss structure reduced the mid-segment stress of the posterior column connecting rod by 18.5％-24.3％during flexion-extension and lateral bending.Endplate stress analysis revealed that the maximum Von Mises stress on the endplate occurred during flexion,with values of 32.54MPa,30.76MPa,and 24.37MPa for the standard,truss,and self-stabilizing structures,respectively.The self-stabilizing structure reduced endplate stress by 14％-30％compared with the other two structures.Analysis of the internal fixation system showed that the cage stress of the self-stabilizing AVB was significantly lower than that of the standard and truss structures:reduced by 57％and 61％in flexion;52％-62％and 59％-64％in lateral bending;and 61％-62％and 46％-61％in rotation,respectively.Conclusions:Compared to the standard structure,the truss structure AVB reduces the stress concentration of the posterior column connecting rod through a multi-segment stress dispersion mechanism.The self-stabilizing structure AVB enhances the stability of the prosthesis-vertebral body interface through screw fixation.

OBJECTIVE To analyze the implementation experience of France’s additional list system for innovative medical products， and to provide reference for China to support medical institutions to use innovative medical products. METHODS Taking France as a case study， using policy analysis method， this paper systematically studied the practice of establishing additional list system to compensate for innovative medical products in France under diagnosis-related group （DRG） payment， including the establishment background， selection procedure and implementation effect. The suggestions were provided on the medical insurance payment methods for innovative medical products in China. RESULTS & CONCLUSIONS The additional list system established a compensation and payment system for innovative medical products with significant clinical efficacy but high treatment cost， covering four stages： application， evaluation， payment and adjustment， which effectively reduced the drug burden on medical institutions， promoted the use of innovative pharmaceutical products by medical institutions， and stimulated the innovation drive of the pharmaceutical industry， but at the same time brought payment pressure to the medical insurance fund. With the rapid spread of our DRG/diagnosis-intervention packet payment reform of China， some regions have also explored the establishment of a compensation and payment mechanism for innovative medical products， but there are still imperfections. We can refer to the implementation experience of the French additional list system and establish an effective compensation and payment system for innovative medical products starting from the establishment of selection criteria， the selection of compensation mode and the implementation of dynamic adjustment.

Objective:To systematically evaluate the effect of repeated low-level red light (RLRL) therapy on controlling the progression of myopia in children.Methods:Medline, Embase, Cochrane Library, Web of Science, ClinicalTrial.gov and the CNKI, VIP, Wanfang database, and Chinese Clinical Trial Registry (www.chictr.org.cn) were searched from their establishment to September 2022 to obtain the randomized controlled trial (RCT) about RLRL controlling myopia progression in children.Grey literature was also searched.Inclusion and exclusion criteria were developed according to the PICOS principle.Two researchers screened the literature independently, extracted data, and assessed the risk of bias in the included studies using the Cochrane collaboration tool for assessing risk of bias.The data were imported into RevMan 5.4 software for meta-analysis.Mean and standard deviation of data were used to obtain mean differences and 95% confidence intervals of included studies.Changes in spherical equivalent (SE) and axial length (AL) were compared between before and after the intervention in RLRL and single-vision spectacle (experimental group) and single-vision spectacle (control group). The GRADE system was used to grade the quality of evidence for the outcome indicators.Results:A total of 157 studies were obtained.After the screening, 7 RCT studies including 1 038 study subjects met the inclusion criteria.Meta-analysis results showed that retarded SE progression was retarded and AL elongation was reduced significantly after different follow-up durations (1, 3, 6, 12 and 24 months) in experimental group compared with control group.As the follow-up duration extended from 1 month to 24 months, the retard of SE progression increased from 0.14 to 0.93 D, and the reduction of AL increased from 0.07 to 0.48 mm.Both 635 and 650 nm red light significantly retarded SE progression and reduced AL elongation.The two outcome indicators, SE change and AL change were moderate-strength evidence by GRADE.Conclusions:The current moderate-strength evidence shows that RLRL can better retard myopia progression in children than single-vision spectacle glasses.

Objective:To investigate the predictive value of F-2-fluoro-2-deoxy-D-glucose ( 18F-FDG) PET-CT metabolic parameters for the recurrence of type 1 autoimmune pancreatitis (AIP). Methods:Eighty-six patients with type 1 AIP who met the International Consensus Diagnostic Criteria (ICDC) and underwent 18F-FDG PET-CT before interventional treatment at the PLA General Hospital between May 2009 and June 2021 were included and divided into recurrence group ( n=43) and no-recurrence group ( n=43) according to whether they recurred after treatment. The standard uptake value (SUV)≥2.5 fixed threshold was used to outline the pancreatic lesion volume of interest (VOI) in three dimensions, and the three-dimensional diameter of the lesion, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), target-to-bench ratio (TBR) and standardized uptake value ratio (SUVR) were measured to compare the clinical characteristics, biochemical indices and treatment of the two groups; univariate and multifactorial regression analysis were used to examine 18F-FDG PET/CT visual indices of pancreatic lesions and extra-pancreatic involved organs as well as metabolic parameters in the two groups. A recurrence prediction model was constructed and its predictive efficacy was assessed. Results:The proportion of patients receiving glucocorticoid maintenance therapy was significantly higher in the no-recurrence group than in the recurrence group (58% vs 23.3%), and the serum IgG4 levels before treatment were significantly higher in the recurrence group [(15 309±11 724) mg/L vs (8 816±7 169) mg/L]. The results of univariate analysis showed that the proportion of extra-pancreatic salivary gland involvement and VOI, SUVmax, SUVpeak, SUVR, TBR, MTV, and TLG were significantly higher in the recurrence group than in the no-recurrence group, and the differences were statistically significant (all P values <0.05); the results of multivariate analysis showed that VOI ( OR=1.012, 95% CI 1.001-1.023 ), SUV max ( OR=1.398, 95% CI 1.029-1.899), SUV peak ( OR=1.408, 95% CI1.002-1.978), SUVR ( OR=1.977, 95% CI1.036-3.771) and MTV ( OR=1.012, 95% CI1.000- 1.022) in the recurrence group were significantly higher than those in the no-recurrence group, and all differences were statistically significant (all P values <0.05). The prediction model was constructed by multifactorial binary logistic regression analysis of SUVR>2, MTV>36 cm 3, and IgG4>11 400 mg/L, which had an AUC of 0.800 (95% CI 0.704-0.897), sensitivity of 81.4% (95% CI 0.661-0.911), specificity of 74.4% (95% CI 0.585-0.860), and prediction accuracy of 77.9%. Conclusions:18F-FDG PET/CT metabolic parameters can be used as predictors of type 1 AIP recurrence; a multiparameter model constructed based on metabolic parameters SUVR, MTV and IgG4 has a good predictive efficacy for predicting type 1 AIP recurrence.

Objective:To evaluate the efficacy and safety of endoscopic biliary drainage for biliary fistula.Methods:Data of consecutive 409 biliary fistula patients who were treated and diagnosed at the First Medical Center of Chinese PLA General Hospital from November 2002 to November 2022 were reviewed, and 53 patients who received endoscopic retrograde cholangiopancreatography (ERCP) drainage were finally included. General information, procedural conditions, clinical outcomes and adverse events were analyzed. The patients were categorized into two groups: the endoscopic retrograde biliary drainage (ERBD) group ( n=46) and the endoscopic nasobiliary drainage (ENBD) group ( n=7). Procedural characteristics, operation outcomes, and operation time were compared between the two groups. Results:There were 36 males and 17 females, with the age of 52.2±12.7 years, among whom 58.5% (31/53) were secondary to cholecystectomy. Clinical success was achieved in 83.0% (44/53) patients, with the operation time of 27.0 (13.5, 33.5) minutes and the treatment session of 1 (1, 2). The time to resolution was 89 (47, 161) days. The success rate of ERCP for low-grade biliary fistula was higher compared with that of high-grade biliary fistula [96.4% (27/28) VS 68.0% (17/25), χ2=7.57, P=0.006]. Bridging drainage achieved higher success rate compared with that of non-bridging drainage [91.7% (33/36) VS 64.7% (11/17), χ2=5.95, P=0.015], while different diameters of stents (≥10 Fr VS <10 Fr) achieved similar success rate [81.8% (27/33) VS 84.6% (11/13), χ2=0.05, P=0.822]. Adverse events occurred in 10 patients (18.9%), including 6 pancreatitis, 2 bleeding, 1 cholangitis and 1 death. Except for 1 death, 9 other adverse events were mild and managed with conservative treatment without interventions. There was no significant difference in clinical success rate [6/7 VS 82.6% (38/46), χ2=0.04, P=0.838] or the median operation time [28.0 min VS 23.0 min, Z=0.38, P=0.774] between ENBD group and ERBD group. Conclusion:Endoscopic biliary drainage is safe and effective for biliary fistula. ENBD and ERBD have comparable clinical efficacy. ERCP for low-grade biliary fistula may achieve a higher success rate, and bridging drainage may facilitate fistula resolution.

Objective:To clarify the anti-inflammatory effects and anti-endoplasmic reticulum stress effects of resolvin D2 (RvD2) in viral myocarditis mice and to explore its possible mechanism.Methods:Fifty male BALB/c mice were collected and assigned corresponding numbers. Then 40 male BALB/c mice were selected randomly with 10 mice in each group. They were set as normal control group, RvD2 control group, viral myocarditis group and RvD2 treatment group. Afterwards, mice in the RvD2 control group received continuous intraperitoneal injection of RvD2 for 7 days, while mice in the viral myocarditis group received intraperitoneal injection of Coxsackievirus B3 virus (CVB3) in the purpose of constructing an animal model of viral myocarditis. Then, mice in the RvD2 treatment group were given continuous intraperitoneal injection of RvD2 for 7 days. After these 7 days, the mice of each group were sacrificed and their cardiac tissue and serum samples were taken. The expression levels of serum inflammatory factors including IL-1β and TNF-α were detected by ELISA in each group of mice, and HE staining were used to detect the inflammatory cell infiltration in myocardial tissue of each group. Meanwhile, the expression levels of inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue in each group of mice were detected by Western blot experiment. The remaining 10 BALB/c mice were treated with intraperitoneal injection of RvD2 as well as GPR18 protein inhibitors after constructing the animal model of viral myocarditis mentioned above. In the end, the expression levels of GPR18 protein, inflammation-related proteins including IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue of each group were detected by Western blot experiments.Results:Compared with the normal control group, the expression levels of inflammatory factors IL-1β and TNF-α in the serum of mice with viral myocarditis were significantly increased, and the degree of infiltration of inflammatory cells in myocardial tissue was also significantly increased. Besides, the expression levels of the inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins including GRP78 and Chop increased largely. While compared with the viral myocarditis group, the expression levels of serum inflammatory factors IL-1β and TNF-α in the mice of the RvD2 treatment group were significantly reduced and the degree of infiltration of inflammatory cells in the cardiac tissue was significantly reduced. Also, the expression levels of inflammation-related proteins IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins GRP78 and Chop were significantly reduced. After intraperitoneal injection of RvD2 and GPR18 inhibitor, in the mice treated with viral myocarditis, the expression levels of IL-1β, TNF-α and endoplasmic reticulum stress-related proteins like GRP78 and Chop in myocardial tissue of these mice significantly increased when it came to compare with the RvD2 treatment group, while the expression levels of GPR18 protein were significantly reduced.Conclusions:RvD2 can inhibit the inflammatory response and endoplasmic reticulum stress injury in mice with viral myocarditis by binding to the membrane protein receptor GPR18, thus exerting a protective effect on heart.