ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

In recent years, endovascular therapy has become the most important progress in the field of the treatment of acute ischemic stroke caused by large vessel occlusion. However, the vascular recanalization shown by imaging after endovascular treatment cannot fully translate into effective tissue reperfusion and functional outcome, a phenomenon known as "futile recanalization". Combined neuroprotective therapy after vascular recanalization is expected to reduce the occurrence of futile recanalization and improve the outcome of patients. This article briefly summarizes the main application progress of commonly used neuroprotective therapies in clinical practice (edaravone dexborneol, glucocorticoids, hypothermia, and remote ischemic conditioning). It explores the trend and direction of combining endovascular therapy and neuroprotective therapy for patients with acute ischemic stroke caused by large vessel occlusion, and provides further reference and suggestions for intervention measures after endovascular therapy.

Objective:To investigate the efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears (IMRCT).Methods:A retrospective case series study was performed on 11 IMRCT patients who were admitted to Affiliated Fuyang Hospital of Bengbu Medical University (Fuyang People′s Hospital) from May 2020 to June 2022, including 7 males and 4 females, aged 54-74 years [(62.6±7.3)years]. All the patients were treated with arthroscopic superior capsular reconstruction using composite patch graft combined with tenodesis of the long head of the biceps tendon. The Visual Analogue Scale (VAS), Acromiohumeral Distance (AHD), Constant-Murley score and University of California Los Angeles (UCLA) score and active range of motion of the shoulder joint before, at 6 months after surgery and at the last follow-up were compared. At the last follow-up, the integrity of reconstructed superior capsule and the long head of the biceps tendon was evaluated using MRI of the shoulder joint. Postoperative complications were observed.Results:All the patients were followed up for 13-39 months [16(13, 36)months]. The VAS score, AHD, Constant-Murley score, and UCLA score were 2(2, 3)points, (9.1±1.1)mm, (56.1±5.4)points, and (19.7±2.8)points respectively at 6 months after surgery, which were all significantly improved from those before surgery [6(5, 7)points, (5.1±1.2)mm, (37.9±2.2)points, and (11.8±1.2)points] ( P<0.05). The VAS score, AHD, Constant-Murley score, and UCLA score were 0(0, 1)points, (8.4±0.9)mm, (83.6±3.8)points, and (28.2±2.3)points respectively at the last follow-up, which were all significantly improved from those before surgery ( P<0.05). At the last follow-up, the VAS score or AHD were not significantly improved from those at 6 months after surgery ( P>0.05); Constant-Murley score and UCLA score were both significantly improved from those at 6 months after surgery ( P<0.05). At 6 months after surgery, shoulder active ranges of motion in forward flexion, abduction and external rotation were (134.6±13.5)°, (124.6±18.6)° and 45(40, 50)° respectively, which were all significantly improved compared with those before surgery [(63.2±36.1)°, (65.0±23.1)°, and [30(20, 40)°] ( P<0.05). At the last follow-up, shoulder active ranges of motion in forward flexion, abduction and external rotation were (144.1±12.6)°, (139.6±15.4)° and 60(45, 65)° respectively, which were all significantly improved compared with those before surgery ( P<0.05). There were no significant differences in active range of motion of the shoulder in forward flexion, abduction and external rotation between 6 months after surgery and the last follow-up ( P>0.05). At the last follow-up, MRI revealed integrity of the reconstructed superior joint capsule and the long head of the biceps tendon in 10 patients. One patient developed resorption of the greater tuberosity and 1 showed a partial tear of the supraspinatus tendon at 1 year after surgery. Conclusion:Arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon can relieve shoulder pain, decrease upward displacement of the humerus head, improve the function and range of motion of the shoulder joint, and reduce complications in the treatment of IMRCT.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

After onset of acute ischemic stroke, nerve cells undergo ischemic necrosis, release endogenous damage related pattern molecules, which activate microglia and astrocytes, and lead to immune inflammatory responses. At the same time, it attracts and chemotactically guide peripheral blood immune cells to infiltrate brain tissue through the damaged blood-brain barrier, further exacerbating brain injury. Studies have shown that the peripheral blood immune cells are closely associated with the outcome of acute ischemic stroke. This article summarizes the mechanism of peripheral immune cells in ischemic brain injury, their correlation with clinical outcome, and possible intervention measures.

Humans ; Female ; Breast Neoplasms/genetics* ; Prognosis ; Gene Expression Profiling ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Receptor, ErbB-2/metabolism* ; Gene Regulatory Networks/genetics*