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 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

Tyrosine kinase inhibitors （TKIs） represent a class of small-molecule targeted drugs that improve the survival time of patients with gastrointestinal stromal tumor （GIST）. Imatinib， sunitinib， regorafenib， ripretinib， and avapritinib are commonly used TKIs in the clinical treatment of various types of GIST. This article provides a comprehensive review of the pharmacokinetics and therapeutic drug monitoring （TDM） of these five drugs， finding that there is significant individual variability in the pharmacokinetics of these drugs. Among them， the absorption of imatinib， regorafenib， and avapritinib are influenced by food intake. Imatinib should be taken with meals and 200 mL of water， regorafenib is taken with a low-fat meal， while avapritinib is taken on an empty stomach. TKIs are mainly metabolized by cytochrome P450 3A4 （CYP3A4）， and when used in combination with CYP3A4 inducers or inhibitors， drug exposure levels will significantly change； apart from metabolic enzymes， the exposure levels of TKIs are also influenced by interactions with the transporter proteins P-glycoprotein and breast cancer resistance protein. Currently， research on TDM for TKIs is still in the exploratory stage， with a substantial amount of literature reporting the effective concentrations of imatinib， sunitinib and regorafenib. However， the precise relationship between exposure levels and efficacy/ toxicity needs further exploration. Currently， there is a lack of research on the correlation between exposure levels and efficacy/ toxicity of ripretinib and avapritinib. It is recommended to implement TDM in patients taking these drugs and explore their therapeutic window in combination with pharmacokinetic models. The commonly used methods for clinical TDM of TKIs include immunoassay， chromatography， and surface-enhanced Raman spectroscopy， providing a technical basis for clarifying the therapeutic window of TKIs.

OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.

Objective:To analyze the clinical characteristics of patients with inflammatory bowel disea-ses(IBD)in pre-pregnancy,pregancy and loctation.Methods:The clinical data of pregnancy compli-cated with IBD in Department of Obstetrics and Gynecology of Peking University Third Hospital and deli-very from September 2011 to June 2022 were collected.The clinical characteristics of the patients were analyzed retrospectively.According to the state of diseases during pre-pregnancy,pregnancy and lactation,the patients were divided into active and remission group,and the two groups were compared interms of pre-pregnancy counseling,nutritional status,pregnancy and delivery complications,gestational week,mode of delivery,and neonatal outcome.Results:A total of 33 pregnant women with IBD were included in this study,of which 7 delivered a second child,for a total of 40 deliveries,with 36 natural pregnan-cies(90.0％)and 4 assisted reproductions(10.0％).Among the 40 cases,21 cases(52.5％)were sustained in remission in pre-pregnancy,pregnancy and lactation,and 19 cases(47.5％)in disease ac-tivity,of which 8 cases(42.1％)were due to self-withdrawal of drugs or failure to take medicine regu-larly.Compared with the activity group,the disease remission group had a higher rate of pre-pregnancy counseling(57.1％vs.15.8％,P=0.010),and higher levels of hemoglobin[(112.67±8.53)g/L vs.(102.84±5.23)g/L,P＜0.001],serum total protein[(66.58±6.34)g/L vs.(60.83±6.25)g/L,P=0.006],serum albumin[36.4(35.1,38.3)g/L vs.34.3(31.1,35.6)g/L,P=0.006],se-rum calcium[(2.25±0.10)μmol/L vs.(2.13±0.15)μmol/L,P=0.004],but a lower incidence of gestational hypertensive disorders(0 vs.31.6％,P=0.007).In 40 deliveries,there were 27 cases of vaginal delivery(67.5％),13 cases of cesarean section(32.5％).The analysis of neonatal outcomes showed 38 full-term deliveries and 2 preterm deliveries;1 case of macrosomia,1 case of small-for-gesta-tional-age,1 case of low birth weight and 3 cases of birth defects.There were 10 newborns admitted to neonatal intensive care unit,including 4 cases of neonatal infections and 2 cases of neonatal jaundice.Conclusion:Pre-pregnancy counseling and evaluation of IBD patients are very important,and good preg-nancy outcomes can be obtained through careful management during pregnancy in the most of the pa-tients.

BACKGROUND:Previous studies have shown that human beta-defensin 3 has significant antifungal,antibacterial,and antiviral activities and plays an important bridging role in linking innate and acquired immune responses. OBJECTIVE:To observe the effect of human beta-defensin 3 hydrogel on treatment of periodontitis in rats. METHODS:Using Poloxamer 188 and 407 as the matrix,a blank hydrogel was constructed by cold solution.Human beta-defensin 3 hydrogel was prepared by mixing human beta-defensin 3 with the hydrogel.Twenty-five SD rats were randomly divided into five groups with five rats in each group:No treatment was given in the healthy group.The periodontitis model was constructed by the orthodontic ligature wire method in the periodontitis group,blank hydrogel group,minocycline hydrochloride group,and human beta-defensin 3 hydrogel group.8 weeks after modeling,blank hydrogel,minocycline hydrochloride,and human β-defensin 3 hydrogel were injected into the buccal and palatal periodontal bags,once a week,and relevant tests were carried out after continuous administration for 4 weeks. RESULTS AND CONCLUSION:(1)Compared with the healthy group,periodontal plaque index,gingival bleeding index,and periodontal probing depth were increased in the periodontitis group(P<0.01).Compared with the periodontitis group,the periodontal plaque index,gingival bleeding index,and periodontal probing depth of rats were decreased in the minocycline hydrochloride group and the human beta-defensin 3 hydrogel group(P<0.05).(2)Hematoxylin-eosin staining proved that the hydrogel was not toxic to the rat organism.(3)Stereomicroscopy and Micro CT showed that compared with the healthy group,the root exposure and the distance between enamel cementum boundary and alveolar crest of the periodontitis group were increased(P<0.05).Compared with the periodontitis group,the root exposure and the distance between enamel cementum boundary and alveolar crest of rats were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group(P<0.05).(4)Hematoxylin-eosin,Masson,and tartrate-resistant acid phosphatase staining showed that periodontal inflammation was obvious,fiber structure was disordered and osteoclasts were active in the periodontitis group and blank hydrogel group,while periodontal inflammation was decreased,fiber arrangement was more regular,and osteoclasts were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group.(5)qRT-PCR showed that compared with the healthy group,the mRNA expressions of interleukin 1β,tumor necrosis factor α,interleukin 6,and inducible nitric oxide synthase were increased in the periodontitis group(P<0.05).Compared with the periodontitis group,the mRNA expressions of interleukin 1β,tumor necrosis factor α,interleukin 6,and inducible nitric oxide synthase in gingival tissue of rats were decreased in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group(P<0.05).(6)The results showed that human beta-defensin 3 hydrogel was able to attenuate inflammation in rat periodontal tissues by decreasing the relative expression of inflammatory factors and inhibiting osteoblasts.

Objective:To establish a clinical laboratory diagnostic pathway for hepatitis C covering diagnosis, differential diagnosis, drug toxicity monitoring, and therapeutic and prognostic evaluation, and to explore a new teaching model for laboratory diagnostics based on the clinical laboratory diagnostic pathway.Methods:According to the clinical diagnosis and treatment guidelines for hepatitis C, laboratory testing strategies for different stages of diagnosis and treatment of the disease were formulated to establish a clinical laboratory diagnostic pathway for hepatitis C. The pathway was applied in the teaching for undergraduate medical students of the seven-year program of grade 2019 of The First Clinical College of Wuhan University, with those of grade 2018 as the control to receive traditional teaching. The teaching effect was compared through questionnaires and quizzes in class. The data were analyzed through the t test with the use of SPSS 19.0. Results:A clinical laboratory diagnostic pathway for hepatitis C recognized by clinicians was established, covering the entire process of clinical diagnosis, differential diagnosis, monitoring of drug side effects, and therapeutic and prognostic evaluation. The students of grade 2019 receiving the pathway-based teaching model had significant improvements in teaching quality evaluation indicators ( P<0.05), with the most marked improvement in "having mastered the key and difficult points of this lesson", with a score of (60.90±2.15) points for grade 2018 and (84.80±3.44) points for grade 2019. The total score for teaching evaluation was significantly higher in students of grade 2019 than in those of grade 2018 [(94.02±4.29) vs. (79.21±3.68)] points, P<0.05). Grade 2019 also had a significantly higher classroom quiz score than grade 2018 (94.60±5.63) vs. (78.10±4.92), P<0.01]. Conclusions:We established and applied a clinical laboratory diagnostic pathway of hepatitis C in the teaching model of laboratory diagnostics, which organically integrates laboratory diagnostics and clinical medicine, and significantly improves the quality of teaching.

Based on the theoretical reflection on the reflective function of medical records,the important findings in the practice of medical records writing in the field of palliative care,and conceptual analysis of narrative medicine tools,combined with empirical investigation materials and analysis,this paper focused on the practice of medical records writing for reflection and research.The main contents include defining the concept of narrative medical records,which are medical records used in clinical practice that incorporate narrative content;clarifying their characteristics and functions at different levels;and exploring practical paths for their application in clinical practice.Based on an in-depth exploration of the uniqueness of narrative medicine practice at Peking Union Medical College,it also emphasized the necessity of writing medical records with narrative thinking.Specifically,it focused on using narrative thinking and forms to enhance the improvement of current medical records writing,and further sought a general framework and multiple possibilities for narrative medicine clinical pathways.

Objective:To explore the clinical effectiveness of a self-designed robot reduction system for femoral intertrochanteric fractures.Methods:A retrospective study was conducted to analyze the 57 patients with intertrochanteric fracture who had been treated at Department of Orthopedics, The Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to February 2023. The patients were divided into a robot group (using the self-designed robot reduction system to assist intramedullary nailing) and a traction bed group (using a traction bed to assist intramedullary nailing) based on their fracture reduction method. The robot group: 31 patients, 11 males and 20 females, with an age of (78.7±9.3) years; 16 left and 15 right sides; 17 cases of type 31-A1, 12 cases of type 31-A2 and 2 cases of type 31-A3 by the AO/OTA classification. The traction bed group: 26 patients, 12 males and 14 females, with an age of (78.7±7.7) years; 13 left and 13 right sides; 16 cases of type 31-A1, 9 cases of type 31-A2 and 1 cases of type 31-A3 by the AO/OTA classification. The 2 groups were compared in terms of reduction and operation time, intraoperative blood loss, fluoroscopy frequency, reduction quality, and VAS and Harris score at preoperation, 1 week and 6 months postoperation.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data ( P>0.05). The robot group was significantly better than the traction bed group in reduction time [(4.4±2.2) min versus (9.4±3.2) min], operation time [(29.0±13.5) min versus (49.3±13.3) min], intraoperative blood loss [(76.5±30.5) mL versus (115.0±38.4) mL], fluoroscopy frequency [(10.2±2.6) times versus (14.8±3.2) times], and good/excellent rate of reduction [80.6% (25/31) versus 50.0% (13/26)] ( P<0.05). All patients were followed up for (6.8±0.3) months. Respectively, the VAS scores at preoperation and 6 months postoperation was (6.2±1.3) and (2.4±0.8) points for the robot group, and (6.3±1.3) and (2.7±0.8) points for the traction bed group, showing no statistically significant differences between the 2 groups ( P>0.05). However, the VAS score was (3.3±1.2) points for the robotic group and (4.8±1.5) points for the traction bed group at 1 week postoperation, showing a statistically significant difference between the 2 groups ( P<0.001). Respectively, the Harris scores at preoperation and 6 months postoperation were (35.3±3.0) and (88.7±3.4) points for the robot group, and (35.6±2.9) and (87.2±3.5) points for the traction bed group, showing no statistically significant differences between the 2 groups ( P>0.05). However, the Harris score was (57.3±3.7) points for the robotic group and (46.7±2.8) points for the traction bed group at 1 week postoperation, showing a statistically significant difference between the 2 groups ( P<0.05). The patient satisfaction rates in the robot and traction bed groups were 96.8% (30/31) and 92.3% (24/26), respectively, showing no statistically significant difference ( P>0.05). Conclusion:Our self-designed robot reduction for femoral intertrochanteric fractures can effectively shorten reduction and operation time, reduce bleeding and fluoroscopy frequency, and enhance anatomical reduction.