HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

With the development of wearable technology, its use in venous thromboembolism (VTE) prevention is of increasing interest to clinical nurses. This paper reviews the technical principles and practical applications of wearable devices in VTE prevention, including the application of electrical stimulation devices and mechanical compression devices, the monitoring of limb activity and physiological parameters, summarizes the advantages of wearable devices in enhancing the efficiency of VTE prevention and patient experience, and discusses the current problems faced and the direction of future research, with the aim of promoting the development of wearable devices in VTE prevention.

With the development of wearable technology, its use in venous thromboembolism (VTE) prevention is of increasing interest to clinical nurses. This paper reviews the technical principles and practical applications of wearable devices in VTE prevention, including the application of electrical stimulation devices and mechanical compression devices, the monitoring of limb activity and physiological parameters, summarizes the advantages of wearable devices in enhancing the efficiency of VTE prevention and patient experience, and discusses the current problems faced and the direction of future research, with the aim of promoting the development of wearable devices in VTE prevention.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

Objective:To investigate the preventive effect of postoperative pancreatic fistula by pedicled omentum wrapping pancreaticojejunostomy in pancreaticoduodenectomy.Methods:The clinical data of 78 patients who underwent pancreaticoduodenectomy in Songjiang Hospital Affiliated to Shanghai Jiao Tong University from September 2017 to August 2020 were retrospectively analyzed. Patients were divided into the modified pancreaticojejunostomy group (conventional approach group, n=43) and the pedicled omentum wrapping pancreaticojejunostomy group (omentum wrapping group, n=35) according to the surgical mode. Postoperative pancreatic fistula, postoperative abdominal bleeding, delayed gastric emptying and postoperative hospital stay were compared between the two groups. Results:Compared with the conventional approach group, the postoperative pancreatic fistula rate in omentum wrapping group was significantly reduced (2.9% vs 18.6%), and the difference was statistically different ( P=0.030); postoperative abdominal bleeding rate(0 vs 4.7%)and the delayed gastric emptying rate were significantly reduced (8.6% vs 25.6%), but both of them were not statistically different ( all P value>0.05); the length of postoperative hospital stay was significantly reduced [(11.3±2.9) days vs (12.8±3.5)days], and the difference was statistically different ( P=0.045). Conclusions:The pedicled omentum wrapping pancreaticojejunostomy was simple and convenient, which can significantly reduce the rate of postoperative pancreatic fistula. It can shorten the time of the length of hospital stay after surgery.

Objective To make classification and segment measurement for the cases with tibiofibular and ankle fractures in parachuting landing, and investigate main classification types of parachuting fractures and fracture segments of high risk.Methods A total of 56 fracture cases in parachuting landing were collected, and the tibiofibula and ankle fractures were classified according to AO-OTA or Lauge-Hansen classification standards respectively based on their digital X-ray images. The medium plane between talus and tibia joint planes in ankle joint was defined as the reference plane. The highest and lowest injury points of tibia and fibula were marked respectively, and the fracture segment was defined between the highest and lowest point for statistical analysis.Results For tibiofibular and ankle fracture cases in parachuting landing, fracture at both tibia and fibula accounted for 80.4%. The major classification of tibiofibula fracture was 42-D/5.2 (45.8%) and 42-D/5.1 (16.7%). The major classification for ankle fracture was pronation-external rotation (PER, 59.4%) and supination-external rotation (SER, 37.5%). When tibiofibular and ankle fracture cases in parachuting landing occurred, the fracture segment of the tibia was mainly from 57 to 143 mm above the reference plane and from 6 mm below the reference plane to 24 mm above the reference plane, while the fracture segment of the fibula was 4-45 mm and 74-83 mm above the reference plane. Injury risks of all above segments were higher than 50%.Conclusions For protection of lower limbs in parachuting landing, the fracture at both tibia and fibula should be highly noticed. The ankle motion of PER and SER should be especially restricted in parachuting ankle protection.

Objective To study the change patterns of bone microstructural parameters around the magnesium based- implants after implantation in rabbit femur at different implantation time points. Methods The threaded and non-threaded high-purity magnesium (HP Mg, 99.99 wt.%) screws, with a 2 mm diameter and a 7 mm length, were implanted into the femoral condyle of the rabbits. The control group was the drilled and healthy group. Micro-CT scanning and analysis were performed at 8th, 12th and 16th week after operation. The obtained microstructural parameters included bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp). Results At 8th week, BMD and BV/TV in non-threaded magnesium screw group were significantly higher than those in healthy group, Tb.N was significantly higher than that in drilled and healthy group, and Tb.Sp was significantly lower than that in healthy group. At 12th week, BMD, BV/TV and Tb.N in threaded magnesium screw group were significantly higher than those in drilled and healthy group, Tb.Th was significantly higher than that in healthy group, and Tb.Sp was significantly lower than that in drilled and healthy group. At 16th week, BMD, BV/TV and Tb.N in non-threaded magnesium screw group were significantly higher than those in drilled and healthy group, and Tb.Sp was significantly lower than that in drilled and healthy group. Conclusions The magnesium based-implant promoted higher BMD, BV/TV, Tb.Th, Tb.N and lower Tb.Sp of surrounding implant, indicating that osseointegration and bone growth were in good condition. Magnesium based-implant could effectively promote the regeneration of bone. The results provide a theoretical basis for the orthopedic application of magnesium based-implants in clinic.

Objective To compare the in vivo degradation rates of two different kinds of high purity magnesium bone screws by animal experiments, so as to make some suggestions on structural design of high purity magnesium bone screws. Methods High purity magnesium bone screws with threads and without threads were implanted into femoral condyles of New Zealand rabbits separately. Twenty-four rabbits were randomly divided into 3 groups. They were euthanized at 8, 12 and 16 weeks after operation, respectively. The in vivo degradation rates of bone screws with two different shapes were compared through micro-CT scanning and Skyscan CT-analyser software, and the stress changes during the progress of bone screw degradation were analyzed. Results The initial surface area of threaded screws ［(31.70±0.06) mm2］ was significantly greater than that of the non-threaded ones ［(29.56±0.22) mm2］. After 8, 12 and 16 weeks, the volume loss ratios of the threaded screws were (26.01±3.44)%, (33.35±5.05)%, (36.84±6.99)%, respectively, and the volume loss ratios of the non-threaded screws were (22.53±4.78)%, (31.12±6.59)%, (43.22±9.31)%, respectively. At the same time point, there were no significant differences in the volume loss ratio between two kinds of screws. The relationship between the volume reduction and the implantation time was linear for non-threaded screws and gradually decreasing for threaded screws. Conclusions Under the low-bearing condition, different structural design for high purity magnesium screws has no obvious effect on their degradation rate in vivo.

This study analyzed the inherent relation between arterial blood mass flow and muscle atrophy of residual limb to provide some necessary information and theoretical support for the clinical rehabilitation of lower limb amputees. Three-dimensional arterial model reconstruction was performed on both intact side and residual limb of a unilateral transfemoral amputee who is the subject. Then hemodynamic calculation was carried out to comparatively analyze the mass flow state at each arterial outlet of both lower extremities. The muscle atrophy ratio of residual limb was calculated by measuring the cross-sectional area of bilateral muscles. Based on the blood supply relationship, the correlation between arterial blood flow reduction ratio and muscle atrophy ratio was discussed. The results showed that the mass flow of superficial femoral arteries and lateral circumflex femoral arteries severely reduced. Meanwhile rectus femoris, vastus lateralis and vastus medialis which were fed by these arteries showed great atrophy too. On the contrary, the mass flow of deep femoral arteries and medial femoral circumflex arteries slightly reduced. Meanwhile gracilis, adductor longus, long head of biceps which were fed by these arteries showed mild atrophy too. These results indicated that there might be a positive and promotion correlation between the muscle atrophy ratio and the blood mass flow reduction ratio of residual limb during rehabilitation.