Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.

Peritoneal fibrosis(PF)is an important reason that restricts long-term treatment of peritoneal dialysis(PD).Based on the theory of collateral disease,PF is considered to be an abdominal collateral disease,with dampness as the main pathogenic factor,and collateral qi deficiency and stagnation,toxicity and blood stasis as the core pathogenesis.The peritoneum is chronically exposed to an inflammatory microenvironment induced by non-biocompatible peritoneal dialysis fluid,reflecting the pathogenic mechanism of dampness-induced pathology.The resultant pathological processes,including damage of peritoneal mesothelial cells,accumulation of inflammatory mediators and metabolic products,and angiogenesis—elucidate the scientific connotation of dampness impairing collaterals and inducing deficiency,toxicity,and stasis.On this basis,the treatment principles of invigorating qi,detoxifying,resolving stasis and unblocking collaterals were proposed,and the Qixue Huazheng prescription was formed with Astragalus as the main ingredient and Centella asiatica and Ligusticum wallichii as the compatibility,which provides a reference for the prevention and treatment of PD-relat-ed PF by traditional Chinese medicine.

OBJECTIVE To investigate the stability of 5-fluorouracil （5-FU） in human blood and to establish a standardized clinical sampling and delivery procedure for therapeutic drug monitoring （TDM） of 5-FU. METHODS The EDTA-anticoagulated whole blood was used as the matrix to prepare stability assessment samples of 5-FU at both low （200 ng/mL） and high （5 000 ng/mL） concentrations （with groups without stabilizer and with 1% volume ratio of stabilizer）. The stability assessment samples were placed under room temperature （[ 25±2） ℃] and refrigerated （2-8 ℃） conditions， with sampling at 0， 0.5， 1， 2， 4， 7， and 24 h. After vortexing and centrifugation， the upper plasma layer was collected； proteins were precipitated using methanol， and the concentration of 5-FU in plasma was determined by liquid chromatography-tandem mass spectrometry. Based on the whole blood stability results， clinical sampling and delivery procedures were established. RESULTS The concentration of 5-FU in blank whole blood samples without stabilizers was significantly lower than that in samples with stabilizers （P＜0.05）. However， varying volumes （10， 25， 50 μL） of stabilizers had no significant effect on the measured concentrations of 5-FU in stability assessment samples with low and high concentrations （P＞0.05）. Without the addition of a stabilizer， low- and high-concentration 5-FU whole blood samples remained stable at room temperature for 0.5 h and 1 h， respectively， and under refrigeration for 2 h and 7 h， respectively. After the addition of a 1% stabilizer， the whole blood samples remained stable for up to 24 h under both room temperature and refrigerated conditions. Based on these findings， the following procedure was established： after collection， whole blood samples could be temporarily stored at room temperature （≤0.5 h） or at 4　℃ （≤2 h）， and transported at 2-8　℃. Upon delivery to the laboratory， a 1% volume ratio of stabilizer must be added immediately， followed by centrifugation within 24 h. The resulting plasma should be stored at －20 ℃ . CONCLUSIONS 5-FU in whole blood exhibits poor stability at room temperature. Refrigeration at 2-8　℃ slightly improves stability ， but degradation still occurs rapidly. Adding a stabilizer at a 1% volume ratio significantly prolongs the refrigerated storage time. The established sampling and transport procedure for 5-FU TDM innovatively introduces the stabilizer addition step at the laboratory sample reception stage （rather than immediately after blood draw）. This approach ensures analytical quality while offering greater adaptability to real-world clinical sampling conditions， significantly improving practical feasibility.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Treatment of large segmental defects of long bone has always been a major challenge for the medical community. At present, the bone defects have been treated by autologous or allogeneic bone grafting, free vascularized fibula grafting, Masquelet technique, Ilizarov technique, cylindrical mesh technique and other methods. However, these technical steps are relatively complicated and their cycles are long so that it is difficult to repair the bone defects immediately after surgery and carry out early weight bearing and functional exercise. In recent years, customized 3D printed microporous titanium (tantalum) prostheses have provided a safe and feasible treatment method for repair of these large bone defects. 3D printed microporous titanium (tantalum) prosthesis can accurately reconstruct the anatomical shape of a bone defect, and simultaneously provide stable biomechanical support for the overall bone structure by its mechanical strength of titanium alloy, demonstrating obvious advantages in the repair and regeneration of bone defects. This paper reviewed the characteristics, design requirements, mechanical properties, vascularization challenges and clinical applications of 3D printed microporous titanium (tantalum) prosthesis, and looked ahead to the future development of this new 3D printed prosthesis.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.

Objective:To evaluate the clinical efficacy of the intelligent robot-assisted fracture reduction system (RAFR) in the treatment of unstable pelvic fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 19 patients with unstable pelvic fracture who had been admitted to Department of Orthopaedics, The 920th Hospital of the Joint Logistics Support Force of the PLA from March to September 2024. There were 11 males and 8 females, with an age of (42.8±13.1) years. The Tile classification: 3 cases of type B1, 5 ones of type B2, 3 ones of type B3, 5 ones of type C1, and 3 ones of type C2. The time from injury to surgery was (9.3±3.5) days. All patients underwent surgery assisted by RAFR. According to the severity of injury, the pelvic posterior ring was fixed in all the 19 patients by sacroiliac joint screws. The anterior pelvic ring was fixed by pubic branch screws in 12 patients, and fixed by pubic branch screws combined with external fixation brackets or simply with external fixation brackets in 7 patients. Variables recorded were surgical time, intraoperative fluoroscopy frequency, intraoperative bleeding volume, fracture reduction quality, pelvic function at the last follow-up, and complications.Results:All the 19 patients achieved successful reduction with the help of RAFR. In this cohort, surgical time averaged (207.2±31.2) minutes, intraoperative bleeding volume 100 (80, 130) mL, fluoroscopy frequency (36.6±12.4) times, and residual pelvic displacement (6.1±3.3) mm. Postoperative reduction quality assessed by the Matta scoring was excellent in 7 cases, good in 9 ones, and fair in 3 ones. The follow-up duration for this cohort was (10.0±2.7) months. By the Majeed system, the pelvic function at the last follow-up scored (85.7±6.3) points, giving 9 excellent and 10 good cases. No such complications as incisional infection, fracture redisplacement, neurovascular injury, or implant loosening/breakage occurred during follow-up.Conclusion:In the treatment of unstable pelvic fractures, the RAFR can lead to good reduction quality and satisfactory clinical outcomes due to its advantages of precision, safety and simple handling.

Objective:To explore the reliability of intraoperative fluoroscopy at lateral 10° and 30° Brodén views in addition to the standard lateral and axial calcaneal views in the lateral decubitus position to assess the quality of articular reduction in calcaneal fractures of Sanders types Ⅱ and Ⅲ.Methods:A retrospective study was conducted to analyze the clinical data of the 74 patients who had been treated at Department of Foot and Ankle Surgery, The People’s Hospital of Linyi for unilateral closed calcaneal fractures of Sanders type Ⅱ or Ⅲ from January 2024, to August 2024. According to the different methods of intraoperative fluoroscopy, the patients were divided into a precision group and a conventional group. In the precision group of 39 cases, intraoperative fluoroscopy was conducted at lateral 10° and 30° Brodén views in the surgery for calcaneal fractures in addition to the standard lateral and axial calcaneal views in the lateral decubitus position; in the conventional group of 35 cases, intraoperative fluoroscopy was conducted only in the standard lateral and axial calcaneal views in the surgery for calcaneal fractures. All patients were treated by traction assisted by external fixation, minimally invasive prying reduction through the tarsal sinus incision, and three-dimensional framework internal fixation. The 2 groups were compared in terms of frequency of intraoperative fluoroscopy; preoperative and postoperative B?hler angles, Gissane angles, and calcaneal varus angles; screw protrusions (more than 2 mm beyond the medial cortex) of the posterior articular surface screw, sustentaculum tali screw, and anterior tuberosity screw; skin irritation symptoms due to the main nail tail (protruding cortex > 1 mm); step-off of the posterior articular surface (more than 2 mm) and wide gap of the posterior articular surface (more than 2 mm).Results:There were no statistically significant differences in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). Both groups showed significant postoperative improvements in X-ray B?hler angle, Gissane angle, and calcaneal varus angle compared with the preoperative values ( P<0.05). There were no statistically significant differences in postoperative X-ray B?hler angle, Gissane angle, or calcaneal varus angle between the 2 groups ( P>0.05). There was no statistically significant difference in the frequency of intraoperative fluoroscopy between the 2 groups either ( P>0.05). The precision group had significantly fewer cases of screw protrusion (more than 2 mm beyond the medial cortex) of the posterior articular surface screw, sustentaculum tali screw, and anterior tuberosity screw, skin irritation symptoms due to the main screw tail (protruding cortex>1 mm), step-off of the posterior articular surface (more than 2 mm), and wide gap of the posterior articular surface (more than 2 mm) on the postoperative CT three-dimensional reconstruction compared with the conventional group ( P<0.05). Conclusion:In surgery for calcaneal fractures of Sanders types Ⅱ and Ⅲ, intraoperative fluoroscopy at lateral 10° and 30° Brodén views in addition to the standard lateral and axial calcaneal views in the lateral decubitus position provides stable and reliable intraoperative monitoring of B?hler angle, Gissane angle, calcaneal varus angle, reduction of the posterior articular surface of the calcaneus and the positions and lengths of implants.