OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

Tissue engineering bone technology, grounded in seed cells, cytokines, and scaffold supports, provides an effective solution for addressing extensive bone defects, demonstrating significant potentials in the field of bone repair. However, this technology still faces numerous challenges. Focusing on vascularization in engineered bones, this article reviews various methods to enhance vascularization within tissue-engineered bones, including multicellular co-culture, application of angiogenic factors, advanced 3D printing, and aid of surgical interventions. This article also analyses the latest research developments and the limitations of the methods, and speculates future research directions for tissue engineered bone.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

OBJECTIVE To explore the construction of a new scientific management model for temporary drug purchase，and to provide a reference for hospitals to improve the level of rational drug use. METHODS Guided by clinical diagnosis and treatment needs and patient medication safety， our hospital carried out the whole process management practice of temporarily purchased drugs by optimizing the review process， creating a review team， formulating pre-audit and post follow-up evaluation standards based on comprehensive drug evaluation， and evaluated the practice effect through the number of temporary purchase applications， implementation rate， drug structure optimization and other indicators. RESULTS Since January 2021， our hospital had implemented a new mode of temporary drug purchase management. By December 2022， clinical pharmacists had reviewed 111 temporary drug procurement applications， effectively intercepted 13 irrational drug use applications （11.71%）， reduced the overall implementation rate of temporary drug procurement by 8.36%，and proposed five batches of drug structure optimization suggestions； 24 drugs were successively introduced such as camrelizumab，sorafenib，busulfan. After optimizing the management mode，the number of temporary drug procurement applications decreased by more than half from 133 in 2019 and 138 in 2020 to 66 in 2021 and 45 in 2022. CONCLUSIONS The model is helpful to optimize the hospital drug catalog， strengthen rational drug use，ensure the safety of patients’ drug use， and fully reflects the professional value of clinical pharmacists in hospital pharmacy management and rational drug use.

OBJECTIVE: To design customized titanium alloy lunate prosthesis, construct three-dimensional finite element model of wrist joint before and after replacement by finite element analysis, and observe the biomechanical changes of wrist joint after replacement, providing biomechanical basis for clinical application of prosthesis. METHODS: One fresh frozen human forearm was collected, and the maximum range of motions in flexion, extension, ulnar deviation, and radialis deviation tested by cortex motion capture system were 48.42°, 38.04°, 35.68°, and 26.41°, respectively. The wrist joint data was obtained by CT scan and imported into Mimics21.0 software and Magics21.0 software to construct a wrist joint three-dimensional model and design customized titanium alloy lunate prosthesis. Then Geomagic Studio 2017 software and Solidworks 2017 software were used to construct the three-dimensional finite element models of a normal wrist joint (normal model) and a wrist joint with lunate prosthesis after replacement (replacement model). The stress distribution and deformation of the wrist joint before and after replacement were analyzed for flexion at and 15°, 30°, 48.42°, extension at 15°, 30°, and 38.04°, ulnar deviation at 10°, 20°, and 35.68°, and radial deviation at 5°, 15°, and 26.41° by the ANSYS 17.0 finite element analysis software. And the stress distribution of lunate bone and lunate prosthesis were also observed. RESULTS: The three-dimensional finite element models of wrist joint before and after replacement were successfully constructed. At different range of motion of flexion, extension, ulnar deviation, and radial deviation, there were some differences in the number of nodes and units in the grid models. In the four directions of flexion, extension, ulnar deviation, and radial deviation, the maximum deformation of wrist joint in normal model and replacement model occurred in the radial side, and the values increased gradually with the increase of the range of motion. The maximum stress of the wrist joint increased gradually with the increase of the range of motion, and at maximum range of motion, the stress was concentrated on the proximal radius, showing an overall trend of moving from the radial wrist to the proximal radius. The maximum stress of normal lunate bone increased gradually with the increase of range of motion in different directions, and the stress position also changed. The maximum stress of lunate prosthesis was concentrated on the ulnar side of the prosthesis, which increased gradually with the increase of the range of motion in flexion, and decreased gradually with the increase of the range of motion in extension, ulnar deviation, and radialis deviation. The stress on prosthesis increased significantly when compared with that on normal lunate bone. CONCLUSION The customized titanium alloy lunate prosthesis does not change the wrist joint load transfer mode, which provided data support for the clinical application of the prosthesis.
Humans ; Lunate Bone/surgery* ; Finite Element Analysis ; Titanium ; Wrist Joint/surgery* ; Artificial Limbs ; Range of Motion, Articular ; Biomechanical Phenomena

OBJECTIVE To provide a reference for safe drug use in clinic. METHODS ADE reports related to nilotinib from the first quarter of 2007 to the fourth quarter of 2022 were collected from the US FDA adverse event reporting system database. The reporting odds ratio （ROR） and proportional reporting ratio （PRR） of disproportionality measures were used to mine potential ADE signals，which were compared with drug instruction and related case report， and were screened and analyzed according to the designated medical events （DME） list formulated by the European Medicines Agency. RESULTS Totally 23 332 cases of ADE with nilotinib as the primary suspected drug were reported. A total of 359 positive signals were obtained，involving 24 system organ classes （SOC），mainly concentrated in various examinations，heart organ diseases，vascular and lymphatic diseases，all kinds of nervous system diseases，etc. Among them，ADEs such as vertebral artery stenosis，coronary artery stenosis，arterial disease，liver infection and the second primary malignant tumor were not mentioned in the instructions. Seven DMEs were detected，of which bone marrow failure，pulmonary hypertension and deafness were not mentioned in the drug instruction. CONCLUSIONS The common ADE signals of nilotinib excavated in this study are consistent with the instructions. In clinical use，special attention should be paid to DME not mentioned in the instructions such as bone marrow failure，pulmonary hypertension and deafness； cardiac function， blood glucose and blood lipid indexes should be monitored closely.