Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

INTRODUCTION: Achieving low-density lipoprotein cholesterol (LDL-C) levels is key to preventing atherosclerotic cardiovascular events. However, many high-risk cardiovascular patients still experience poor LDL-C goal attainment and receive suboptimal lipid-lowering therapy (LLT) prescriptions. Herein, we evaluated LLT prescription patterns, LDL-C goal attainment and cardiovascular mortality among this population group in Singapore. METHODS: This prospective observational cohort study included 555 patients with ischaemic heart disease (IHD) admitted to the hospital in 2020. The LLT prescriptions, corresponding LDL-C levels and cardiovascular outcomes were assessed over a 24-month period. RESULTS: Most participants were male (82.3%), with 48.5% identified as Chinese. High-intensity statin prescriptions increased from 45.4% at hospital admission to 87.1% at discharge and remained stable at approximately 80% at 6, 12, and 24 months post-discharge. Combination LLT prescriptions increased from 12.3% at discharge to 33.8% by 24 months. Ezetimibe was the most commonly prescribed second-line LLT (40.8%), followed by inclisiran (1.09%) and anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapies (0.87%). Over 24 months, LDL-C goal attainment rates were 22.1% for LDL-C < 1.4 mmol/L and 47.2% for LDL-C < 1.8 mmol/L. Multivariable Cox proportional hazards regression indicated that achieving LDL-C < 1.8 mmol/L goal was associated with a reduction in all-cause mortality at 24 months (hazard ratio 0.53, 95% confidence interval 0.30-0.94, P = 0.030). CONCLUSION Treatment gaps in lipid management persist in 80% of the study population, indicating that statin monotherapy alone is insufficient to achieve LDL-C goals. Greater efforts to improve LDL-C goal attainment rates in high-risk cardiovascular patients are imperative.
Humans ; Male ; Cholesterol, LDL/blood* ; Female ; Myocardial Ischemia/drug therapy* ; Middle Aged ; Prospective Studies ; Aged ; Singapore/epidemiology* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Ezetimibe/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective: To explore the relationship between dieting and binge eating with non suicidal self-injury (NSSI) among secondary vocational school students, so as to provide a scientific basis for the development of effective interventions to prevent NSSI. Methods: From October to December 2023, 2 364 students were selected by stratified cluster random sampling method from nine secondary vocational schools in Guizhou Province to conduct a self administered questionnaire survey. Unconditional binary Logisitic regression was used to analyze the relationship between dieting, binge eating behaviours, and the co-occurrence of the two and NSSI among secondary vocational school students, and were stratified by sex. Results: The detection rate of NSSI among secondary vocational school students in Guizhou Province was 27.5%, 6.8% of secondary vocational school students reported dieting, 10.5% reported binge eating behaviour, and 2.9% showed both dieting and binge eating behaviours. The adjusted model of unconditional binary Logistic regression showed that the presence of dieting ( OR =2.37), binge eating behaviour ( OR =2.31), and the co-occurrence of both ( OR =2.60) were associated with higher risk of NSSI among secondary vocational school students; stratified analysis by gender showed that both males and females with dieting, binge eating and coexistence of dieting and binge eating behaviours were at increased risk of NSSI (females: OR =2.27, 2.26, 2.78 ; males: OR =2.15, 2.08, 2.02) ( P <0.01). Conclusions Dieting and binge eating behavior of secondary vocational school students will increase the risk of NSSI. When preventing and intervening NSSI problems of secondary vocational school students, it should pay more attention to eating habits.

Objective:To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation.Methods:Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization.Results:ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions:This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

High-voltage pulsed electric field(HV-PEF)ablation technology has demonstrated promising applications in the clinical treatment of chronic obstructive pulmonary disease(COPD).However,its use has been limited to exploratory applications in a small number of cases,and the underlying mechanisms remain largely undefined.To facilitate broader clinical implementation,comprehensive molecular mechanism studies via extensive animal experimentation are essential.Rats,due to their ease of modeling COPD and the availability of comprehensive molecular reagents,serve as an optimal model for such studies.Consequently,the development of electrodes specifically designed for HV-PEF respiratory ablation in SD rats is of significant importance.In this study,we meticulously examined the anatomical structure of rat airways and investigated various equipment parameters,including material composition,rigidity,diameter,electrode ring dimensions,spacing between positive and negative poles,insulation coating for the catheters,welding techniques between the guidewire and electrode ring,and the design of vent holes in the catheter.Based on these considerations,we fabricated PVC ablation electrode catheters with integrated ventilation functionality.Subsequently,we employed finite element simulation to estimate the field strengths that could be applied by these electrodes.The simulation results were then validated in normal rats to assess the electrical safety and efficacy of the electrodes.These findings laid the groundwork for further investigation into the mechanisms of HV-PEF treatment for COPD.