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.

Objective:To investigate the effects and mechanism of very long chain acyl-CoA dehydrogenase(VLCAD)on prolifera-tion,invasion and metastasis of oral squamous cell carcinoma cells.Methods:The expression levels of VLCAD and glucose trans-porter 1(GLUT1)in human normal oral epithelial cell line(HOEC cells)and human oral squamous cell carcinoma line(SCC25 cells)were determined by Western blot,and the expression levels of VLCAD and GLUT1 in oral squamous cell carcinoma patients and their correlation with pathological stages and prognosis were analyzed in the TCGA database.SCC25 cell lines with VLCAD over-expression and knockdown were constructed and the expression level of VLCAD and GLUT1,cell proliferation,migration,invasion ability,lactate dehydrogenase content and lactate production level were detected respectively.Results:The expression level of VL-CAD in SCC25 cells was significantly lower than that in HOEC cells.The expression level of GLUT1 in SCC25 cells was significantly higher than that in HOEC cells.There was a significant negative correlation between the two expression levels(P＜0.05).VLCAD overexpression significantly inhibited GLUT1 expression and aerobic glycolysis in SCC25 cells,and also inhibited cell proliferation,migration and invasion.VLCAD knockdown effectively reversed the antitumor effects of overexpression mediated by VLCAD(P＜0.05).Conclusion:VLCAD inhibits proliferation,invasion,and metastasis of oral squamous cell carcinoma SCC25 cells by down-regulating GLUT1 and inhibiting its mediated aerobic glycolysis.

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

Objective To investigate the clinical manifestations,risk factors,treatment strategies and clinical prevention feasibility of diabetic ketoacidosis(DKA)after coronary artery bypass transplantation(CABG).Methods Clinical data of 9 patients with ketoacidosis after CABG surgery treated and treated by CICU in the Intensive Care Unit of Cardiac Surgery in Nanjing Gulou Hospital from January 2022 to January 2024 were retrospectively analyzed,and the diagnosis and treatment process and short-term postoperative follow-up were conducted to evaluate the causes of ketoacidosis in order to obtain clinical characteristics.To provide early warning information for follow-up diagnosis and treatment,and to evaluate the effect of perioperative corrective treatment strategy on the short-term prognosis of patients.Results The median duration of DKA in the 9 patients was 2.6 days after surgery,and the clinically suggestive symptoms were tachyarrhythmia(8/9),hypotension(4/9),polyuria(6/9),intractable hyperglycemia(3/9),and derangation(5/9).Analysis of concomitant manifestations or risk factors were mainly the perioperative use of sodium-glucose cotransporter 2 inhibitors(SGLT2i)(9/9),age＞60 years old.The main diagnosis was based on abnormal blood ketone and urine ketone.Blood gas analysis suggested metabolic acidosis,and BE showed serious negative performance.After early diagnosis,8 patients took the volumetric surplus strategy,and the average correction time was 5.6 days.One patient was slow to correct and eventually died from other types of severe complications.Conclusion Perioperative use of SGLT2-i drugs in CHD patients with heart failure and type 2 diabetes is a high risk factor for DKA.The strategy of early diagnosis and parallel capacity surplus is an important way to correct DKA.

Objective To analyze the procurement data of lipid-lowering drugs in hospitals at different levels in Jiangsu Province from October 2019 to September 2023,to evaluate the impact of the volume-based procurement(VBP)policy,and to provide references for clinical rational drug use and healthcare policy optimization.Methods Based on procurement data from the Jiangsu Provincial Health Information Center,statistical analyses of procurement expenditures,defined daily doses(DDDs),and defined daily cost(DDC)were conducted.Mixed-effects models were applied to assess changes in procurement expenditures,DDDs,and DDC before and after VBP implementation.Results From 2019 to 2023,statins dominated the market in Jiangsu Province,with rosuvastatin recording the highest DDDs(748 million).Statins,traditional Chinese medicines,and cholesterol absorption inhibitors ranked highest in procurement expenditures.Tertiary hospitals accounted for the largest share of usage(47.6%)and expenditures(55.8%),while secondary hospitals had the lowest DDC(1.22 yuan)and tertiary hospitals the highest(1.89 yuan).Post-VBP,procurement expenditures and DDC decreased by 53.9%and 35.4%,respectively.Primary hospitals showed the largest expenditure reduction(61.6%),and secondary hospitals exhibited the greatest DDC decline(53.9%).DDDs increased significantly in primary care settings(e.g.,pitavastatin surged by 239.79%in secondary hospitals),while tertiary hospitals saw reduced usage of some drugs(e.g.,amlodipine/atorvastatin decreased by 7.34%).Mixed-effects models confirmed that VBP significantly reduced expenditures(OR=-1.07,P<0.01)and DDC(OR=-2.70,P<0.01)while indirectly lowering prices of non-VBP drugs.After covariate adjustment,expenditure reductions for rosuvastatin and atorvastatin narrowed,ezetimibe expenditures increased(OR=0.13,P<0.01),and pitavastatin usage declined(OR=-0.10,P<0.01).Changes in amlodipine/atorvastatin and ezetimibe lacked statistical significance due to short VBP implementation periods.Tertiary hospitals demonstrated the strictest policy adherence,with the largest expenditure and DDC reductions(P<0.01).Subgroup analysis revealed that the policy did not significantly affect clinical demand(DDDs)in hospitals at different levels,though it was considered to have triggered adjustments in medication structure.Conclusion Jiangsu's lipid-lowering drug structure aligns with guidelines(statin-based,moderate-intensity preference).VBP effectively reduced costs,with tertiary hospitals prioritizing originator-to-generic substitution and primary hospitals reflecting cost-control and demand variations.Confounding factors influenced policy evaluation.The study recommends continuous monitoring and policy optimization to enhance procurement efficiency,ensure rational clinical use,and sustain cost savings,providing insights for further healthcare reform.

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 evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time

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