Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.

OBJECTIVE: To compare the effectiveness and shoulder function of reverse total shoulder arthroplasty (RTSA) and open reduction and internal fixation (ORIF) in the treatment of Neer three/four-part proximal humeral fractures in the elderly. METHODS: Randomized controlled analysis was conducted on 68 patients over 70 years old with Neer three/four-part proximal humeral fractures treated with RTSA or ORIF between January 2020 and June 2022. The patients were randomly divided into RTSA group ( n=32) and ORIF group ( n=36). There was no significant difference ( P>0.05) in the baseline data such as age, gender, body mass index, injured side, Neer classification, and preoperative Charlson comorbidity index, visual analogue scale (VAS) score, Constant shoulder score, Oxford shoulder score (OSS), and hemoglobin (Hb). The operation time, intraoperative blood loss, reduction of Hb on the 3rd day after operation, hospital stay, total cost of hospitalization, complication incidence, range of motion of shoulder joint at 2 years after operation, VAS score before operation and at 5 days and 1 month after operation, Constant shoulder score and OSS score before operation and at 2 years after operation, and imaging results during follow-up were recorded and compared between the two groups. RESULTS: Compared with the ORIF group, the RTSA group had longer operation time, less intraoperative blood loss, and higher total cost of hospitalization ( P<0.05). There was no significant difference in Hb reduction on the 3rd day after operation between the two groups ( P>0.05). The VAS scores significantly improved in both groups at 5 days and 1 month after operation ( P<0.05), but there was no significant difference between the two groups ( P>0.05). All patients were followed up 26-35 months, with an average of 31.2 months. In the RTSA group, there were 2 cases of poor healing of superficial incision and 1 case of transient nerve injury. There was no complication such as bone resorption around the prosthesis, lucent band, prosthesis loosening, or periprosthetic fracture in all patients. In the ORIF group, there was 1 case of poor healing of superficial incision, 3 cases of nonunion of fracture, 1 case of arthritis secondary to humeral head necrosis, and 1 case of bone absorption of large tuberosity, and no displacement or fracture failure of internal fixation was found in all patients. There was no significant difference in the incidence of complications [9.4% (3/32) vs 16.7% (6/36)] between the two groups [ OR (95% CI): 0.828 (0.171, 4.014), P=0.814]. In the RTSA group, 28 cases were graded 0 and 4 cases were graded 1 at 2 years after operation. Constant and OSS scores of RTSA group were significantly better than those of ORIF group ( P<0.05). The Constant score was significantly better than ORIF group in activity and strength, range of motion, lifting, abduction, and external rotation ( P<0.05), and there was no significant difference in pain, daily function, and internal rotation between the two groups ( P>0.05). The RTSA group had a significantly greater range of motion in lifting, abduction, and external rotation than ORIF group ( P<0.05), but there was no significant difference in internal rotation between the two groups ( P>0.05). CONCLUSION Application of RTSA as the initial treatment of Neer three/four-part proximal humeral fractures in the elderly can achieve better rehabilitation of joint activity and lower risk of early reoperation, and improve the quality of life of elderly fracture patients. However, the difficulty of revision and the high cost of treatment require the surgeon to pay full attention and strictly grasp the indications.
Humans ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Shoulder Fractures/surgery* ; Arthroplasty, Replacement, Shoulder/methods* ; Aged ; Bone Plates ; Open Fracture Reduction/methods* ; Range of Motion, Articular ; Treatment Outcome ; Shoulder Joint/physiopathology* ; Aged, 80 and over ; Operative Time ; Postoperative Complications/epidemiology* ; Length of Stay

OBJECTIVE: To design a series of geometric indexes, which can improve the correlation between geometric parameters and dosimetric parameters. METHODS: 48 cases of upper abdomen were selected. Manual and automatic segmentation were performed for two organs at risk, which were stomach and duodenum. Three overlapping structures, which were the overlaps with target expanded by 5 mm, 10 mm and 20 mm, were generated for each organ at risk. The geometric parameters of overlapping structures were calculated. The relationship between these geometric parameters and the dosimetric parameters of organs was investigated. RESULTS: When the geometric parameters of overlapping structures related to the target expand 5 mm, 10 mm and 20 mm were larger than 0.4, 0.6 and 0.8 respectively, the maximum dose differences of manual and automatic segmentation were less than 3 Gy. For the case with no overlaps between the organs and the target expansions, the overlap structure corresponding to target expanding 20 mm were recommended for safety considerations. CONCLUSIONS For organs at risk in the upper abdomen, the overlapping geometric parameters were closely related to the maximum dose of organs. Overlapping geometric parameters could predict whether the difference of maximum dose caused by automaticsegmentation was clinically acceptable or not.
Organs at Risk ; Radiometry ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated

BACKGROUND:Current research on mesenchymal stem cels (MSCs) is mostly focused on its immune regulatory function, while little is reported on the antioxidant capacity of the cels and culture supernatant.OBJECTIVE: To investigate the anti-oxidative capacity of the supernatant harvested from human fetal placenta MSCs (fPMSCs) under a condition of serum free culture. METHODS:fPMSCs were cultured with serum free media, and the supernatants of cels at passages 2-6 were colected at 48 hours after culture. Vitamin C was added into the culture medium, as a positive control, and its concentration was 100 μmol/L. The total antioxidant capacity, scavenging capacity of free radicals and antioxidant enzymatic activities of supernatants were measured. RESULTS AND CONCLUSION: By comparing anti-oxidative activities of vitamin C and na?ve culture medium, supernatants colected from fPMSCs cultures exhibited obvious antioxidant capacities at different extents between passages of cel cultures. The total antioxidant capacity of the culture supernatant was comparable to 40-80 μmol/L vitamin C. In addition, al supernatants derived from cels with different passages displayed capacities to scavenge free radicals, including 2,2-diphenyl-1-picrylhydrazyl radical (DPPH?), hydroxyl radical (?OH), superoxide anion radical (O2-). Even more, activities of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, were also detected in supernatants colected from different passages of fPMSCs. Under the serum-free condition, the culture supernatants of fPMSCs have antioxidant capacities at certain extent. However, the antioxidant components and underlying mechanisms need to be further studied.

Amyloidosis ; Cardiomyopathy, Hypertrophic ; Humans