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 compare the dosimetric and radiobiological differences of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) in craniospinal irradiation. Methods The CT images of 15 patients who received craniospinal irradiation in our hospital were selected. The target volumes and organs at risk (OARs) were contoured, and HT and VMAT plans were designed. The dosimetric parameters of the two plans were compared. A Matlab program based on equivalent uniform dose was developed to calculate the normal tissue complication probability (NTCP). The NTCP values of the two plans were compared. Results The homogeneity index of the target volume in the HT group was better than that in the VMAT group, with values of 0.06 ± 0.01 and 0.08 ± 0.24, respectively, and the difference was statistically significant (P=0.03). However, there was no significant difference in the conformity index of the target volume (P>0.05). There were significant differences in key indicators (D_mean, V₅, D_max) of the lungs, liver, lens, and eyeballs between the two groups (P<0.05). Regarding OARs, the NTCP values of the lens, optic chiasm, lungs, and liver in the HT and VMAT groups were as follows: 0.04 ± 0.03 vs. 0.1 ± 0.06 in the left lens, 0.04 ± 0.06 vs. 0.1 ± 0.07 in the right lens, 0.16 (0.14-0.17) vs. 0.21 (0.18-0.24) in the optic chiasm, 3.89 × 10⁻⁴ (2.45 × 10⁻⁴-7.3 × 10⁻⁴) vs. 8.95 × 10⁻⁴ (5.19 × 10⁻⁴-1.75 × 10⁻³) in the lungs, and 3.45 × 10⁻⁸ (6.0 × 10⁻⁹-1.036 × 10⁻⁷) vs. 9.54 × 10⁻⁸ (1.70 × 10⁻⁸-2.056 × 10⁻⁷) in the liver; the HT group was superior to the VMAT group, and all differences were statistically significant (P<0.05). The NTCP values of the heart in the two groups were 1.35 × 10⁻⁸ (6.34 × 10⁻⁹-2.06 × 10⁻⁹) vs. 5.06 × 10⁻⁹ (2.29 × 10⁻⁹-7.9 × 10⁻⁹), significantly lower in the VMAT group than in the HT group (P<0.05). Conclusion HT has high homogeneity and consistency. The two plans have their own advantages in OAR protection. For OARs with no significant differences in physical dosimetry, NTCP results can be used as a reference. Therefore, comparing the dosimetric parameters and OAR NTCP of HT and VMAT plans can help select the optimal clinical treatment strategy.

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 compare the diagnostic values of different detection methods for respir-atory pathogens in children with acute respiratory infections.Methods A total of 862 children with a-cute respiratory infections were enrolled,and their throat swab samples were tested for seven common respiratory pathogens by the dual amplification method and a self-built nucleic acid detection system.For samples with inconsistent results between the two methods,nested polymerase chain reaction(PCR)was performed for verification.Results The positive detection rate of the dual amplification method was 57.75％,which was significantly higher than 30.14％of the self-built nucleic acid detec-tion system,and the detection rate of mixed infections was 10.14％,which was also significantly high-er than 1.97％of the self-built nucleic acid detection system(P＜0.05).The sensitivity of the dual amplification method was 91.63％,which was significantly higher than 72.61％of the self-built nu-cleic acid detection system,and the specificity was 92.31％,which was also significantly higher than 75.62％of the self-built nucleic acid detection system(P＜0.05).Conclusion The dual amplifica-tion method can simultaneously detect the ribonucleic acid of seven respiratory pathogens with high sensitivity and specificity,demonstrating significant clinical application value.

Left ventricular assist device (LVAD) serves as a critical therapeutic option for patients with end-stage heart failure, significantly enhancing survival rates and quality of life. However, LVAD implantation exerts complex and profound effects on right ventricular (RV) function, with RV dysfunction emerging as a key factor influencing the prognosis of LVAD patients. This article systematically reviews the relationship between LVAD and RV function, exploring the importance of RV function in LVAD patients, assessment methods, underlying mechanisms of impact, and strategies for prevention and management. Comprehensive evidence suggests that preoperative evaluation of RV function is crucial for predicting the risk of RV dysfunction, while effective prevention and management rely on preoperative optimization, meticulous intraoperative techniques, rigorous postoperative monitoring, and multidisciplinary collaboration. Furthermore, this review discusses the potential and future directions of emerging technologies, such as improved LVAD designs, biventricular assist devices, gene therapy, and personalized medicine, in ameliorating RV dysfunction. In conclusion, RV function is one of the key determinants of successful LVAD therapy. Through comprehensive assessment, prevention, and management of RV function, coupled with the application of novel technologies, the clinical outcomes of LVAD patients can be further improved.

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

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Osteoporotic distal radius fracture (ODRF), a common fragility fracture in elderly patients, poses a significant threat to patients′ life and health due to its high incidence and disability rate. Both traditional Chinese medicine and Western medicine have accumulated extensive clinical experience in the diagnosis, treatment and rehabilitation of ODRF. However, there is currently a lack of specific guideline on how to effectively integrate the strengths of the two medical systems. To standardize the collaborative diagnosis and treatment of ODRF using integrated traditional Chinese and Western medicine, the Clinical Practice Guideline Working Group for the clinical practice guideline for the diagnosis and treatment of osteoporotic distal radius fracture through integrated traditional Chinese medicine and Western medicine was established in September 2024, led by the Third Affiliated Hospital of Yunnan University of Chinese medicine (Kunming Hospital of Chinese Medicine) with the participation of many medical institutions across China. Protocol for the guideline was then formulated to detail each key aspect in the development of the guideline and explain the related procedures, aiming to ensure a standardized, orderly and transparent development.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.