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OBJECTIVE@#To compare the biomechanical stability of three cross-bridge headless compression screws and locking plates in the fixation of Mason type Ⅲ radial head fractures by finite element method.@*METHODS@#Using reverse modeling technology, the radial CT data and internal fixation data of a healthy 25-year-old male were imported into the relevant software. Three-dimensional finite element model of 3 cross-bridge headless compression screws and locking plates for MasonⅢ radial head fractures were established, and the radial head was loaded with 100 N axial loading. The maximum displacement, maximum Von Mises stress and stress distribution of the two groups were compared.@*RESULTS@#The maximum displacements of the three cross-bridge screws group and locking plate group were 0.069 mm and 0.087 mm respectively, and the Von Mises stress peaks were 18.59 MPa and 31.85 MPa respectively. The stress distribution of the three screws group was more uniform.@*CONCLUSION@#Both internal fixation methods can provide good fixation effect. CoMPared with the locking plate fixation method, the 3 cross-bridge headless compression screws fixation is more stable and the stress distribution is more uniform.
الموضوعات
Male , Humans , Adult , Finite Element Analysis , Radial Head and Neck Fractures , Bone Screws , Biomechanical Phenomena , Radius Fractures/surgery , Fracture Fixation, Internal/methods , Bone Plates , Fractures, Comminutedالملخص
BACKGROUND:Osteochondral defect of the joint is a difficult problem faced by orthopedic surgeons,and traditional repair methods are difficult to obtain satisfactory curative effects.Hydroxyapatite-polyvinyl alcohol-based composite hydrogel material is a direction of current research. OBJECTIVE:To prepare hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material and characterize its physical characteristics,to verify its histocompatibility and cell adhesion and proliferation ability after implantation in vivo,and explore its repair effect on rabbit osteochondral defects. METHODS:The cylindrical porous poly(lactic acid)scaffold was prepared by 3D printing technology(the pore sizes were 1.2,1.4,1.6 and 1.8 mm,respectively).The poly(lactic acid)scaffold was injected with polyvinyl alcohol and hydroxyapatite mixed emulsion.After freezing thawing and dichloromethane dissolution,hydroxyapatite-polyvinyl alcohol hydrogel was prepared.Then,the collagen-chitosan-gelatin mixture was injected into the hydroxyapatite-polyvinyl alcohol hydrogel and crosslinked with genipin.Finally,the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel was prepared by alcohol cleaning and freeze-drying.The physical characteristics of the four groups of hydrogels were characterized,and the hydrogels with the best performance were screened for follow-up experiments.Hydroxyapatite-polyvinyl alcohol hydrogel and collagen-chitosan-gelatin composite hydrogel were implanted subcutaneously in SD rats.Hematoxylin-eosin staining and Masson staining were used to observe the adhesion growth of cells on the material surface.Osteochondral defect(diameter:5 mm,depth:6 mm)models were made in the femoral trochlea of bilateral knee joints of 15 rabbits.The composite hydrogel was implanted on the left side(experimental group),while no material was implanted on the right side(control group).Micro-CT and histology were used to evaluate the repair effect of osteochondral defects. RESULTS AND CONCLUSION:(1)Based on the results of porosity,water content,mechanical testing and scanning electron microscopy,it was concluded that the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel with a pore size of 1.2 mm was more consistent with the general characteristics of natural cartilage,which was used for subsequent experiments.(2)Hematoxylin-eosin staining and Masson staining exhibited that with the extension of subcutaneous implantation time of the materials,the adhesion of cells around the two materials increased significantly,and the proliferation of cells after the implantation of collagen-chitosan-gelatin was better,a large number of cells could be seen growing into the formed network structure,and the network structure was gradually degraded.(3)In the rabbit osteochondral defect experiment,8 weeks after surgery,Micro-CT examination demonstrated that the material implanted in the experimental group had good integration with the surrounding bone-cartilage,with some bone growth on the surface and inside,while the cartilage and subcartilage in the control group still had obvious defects,without effective repair.Hematoxylin-eosin staining and toluidine blue staining displayed that the composite hydrogel in the experimental group integrated with the surrounding articular cartilage 4-8 weeks after implantation.With the extension of time,new cartilage gradually formed on the surface of the material.At 12 weeks,most of the defect was covered by new cartilage,and good bone growth was also observed in the subcartilage.In the control group,the deep bone defects were mostly repaired and the superficial cartilage and subchondral bone defects were also repaired to a certain extent,but they were mainly replaced by fibrous tissue and part of fibrocartilage 12 weeks after surgery.(4)In conclusion,hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material can mimic the structure and function of natural cartilage,and can effectively repair osteochondral defects in animal experiments.
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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.
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Di-(2-ethylhexyl) phthalate (DEHP) is currently one of the most widely used plasticizers, widely found in all kinds of items, such as children’s toys and food packaging materials, but also added to wallpaper, cable protective agents and other building decoration materials. DEHP is toxic and absorbed by the human body through respiratory tract, digestive tract and skin contact, which can cause damage to multiple systems, especially the male reproductive system, and testis is an important target organ. Oxidative stress injury is the core mechanism of spermatogenesis disorder caused by DEHP. DEHP exposure can cause oxidative stress or reactive oxygen species (ROS) increase in germ cells, and on this basis, promote cell apoptosis or cause excessive autophagy. The toxicity of DEHP to Leydig cells is mainly to interfere with the synthesis of steroid hormones. For Sertoli cells, ferroptosis and destruction of the blood-testis barrier are common injury mechanisms. In addition, gene methylation caused by DEHP not only affects the spermatogenic process, but also has epigenetic effects on offspring. In this paper, we reviewed the pathological damage, germ cell toxicity and epigenetic effects of DEHP on testis, and focused on the damage and molecular mechanism on testicular spermatogenic cells, Leydig cells and Sertoli cells. Future research is required to elucidate the body’s clearance mechanism and treatment plan after exposure to DEHP and whether DEHP will damage the function of myoid cells. It is hoped that this can provide new ideas for prevention and treatment of male reproductive disorders resulting from long-term exposure to plastic products.
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ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.
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OBJECTIVE@#To investigate the accuracy, safety, and short-term effectiveness of a domestic robot-assisted system in total knee arthroplasty (TKA) by a multicenter randomized controlled trial.@*METHODS@#Between December 2021 and February 2023, 138 patients with knee osteoarthritis who received TKA in 5 clinical centers were prospectively collected, and 134 patients met the inclusion criteria were randomly assigned to either a trial group ( n=68) or a control group ( n=66). Seven patients had lost follow-up and missing data, so they were excluded and the remaining 127 patients were included for analysis, including 66 patients in the trial group and 61 patients in the control group. There was no significant difference ( P>0.05) in gender, age, body mass index, side, duration of osteoarthritis, Kellgren-Lawrence grading, preoperative Knee Society Score (KSS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score between the two groups. The trial group completed the TKA by domestic robot-assisted osteotomy according to the preoperative CT-based surgical planning. The control group was performed by traditional osteotomy plate combined with soft tissue release. Total operation time, osteotomy time of femoral/tibial side, intraoperative blood loss, and postoperative complications were recorded and compared between the two groups. The radiographs were taken at 5 and 90 days after operation, and hip-knee-ankle angle (HKA), lateral distal angle of femur (LDFA), and posterior tibial slope (PTS) were measured. The difference between the measured values of the above indexes at two time points after operation and the preoperative planning target values was calculated, and the absolute value (absolute error) was taken for comparison between the two groups. The postoperative recovery of lower limb alignment was judged and the accuracy was calculated. KSS score and WOMAC score were used to evaluate the knee joint function of patients before operation and at 90 days after operation. The improvement rates of KSS score and WOMAC score were calculated. The function, stability, and convenience of the robot-assisted system were evaluated by the surgeons.@*RESULTS@#The total operation time and femoral osteotomy time of the trial group were significantly longer than those of the control group ( P<0.05). There was no significant difference in the tibial osteotomy time and the amount of intraoperative blood loss between the two groups ( P>0.05). The incisions of both groups healed by first intention after operation, and there was no infection around the prosthesis. Nine patients in the trial group and 8 in the control group developed lower extremity vascular thrombosis, all of which were calf intermuscular venous thrombosis, and there was no significant difference in the incidence of complications ( P>0.05). All patients were followed up 90 days. There was no significant difference in KSS score and WOMAC score between the two groups at 90 days after operation ( P>0.05). There was significant difference in the improvement rate of KSS score between the two groups ( P<0.05), while there was no significant difference in the improvement rate of WOMAC score between the two groups ( P>0.05). Radiological results showed that the absolute errors of HKA and LDFA in the trial group were significantly smaller than those in the control group at 5 and 90 days after operation ( P<0.05), and the recovery accuracy of lower limb alignment was significantly higher than that in control group ( P<0.05). The absolute error of PTS in the trial group was significantly smaller than that in the control group at 5 days after operation ( P<0.05), but there was no significant difference at 90 days between the two groups ( P>0.05). The functional satisfaction rate of the robot-assisted system was 98.5% (65/66), and the satisfaction rates of stability and convenience were 100% (66/66).@*CONCLUSION@#Domestic robot-assisted TKA is a safe and effective surgical treatment for knee osteoarthritis, which can achieve favorable lower limb alignment reconstruction, precise implant of prosthesis, and satisfactory functional recovery.
الموضوعات
Humans , Arthroplasty, Replacement, Knee/methods , Osteoarthritis, Knee/surgery , Blood Loss, Surgical , Robotics , Knee Joint/surgery , Knee Prosthesis , Retrospective Studiesالملخص
Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
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Humans , Mesothelioma, Malignant , Prognosis , Nomograms , Retrospective Studies , Proportional Hazards Modelsالملخص
Chitosanases represent a class of glycoside hydrolases with high catalytic activity on chitosan but nearly no activity on chitin. Chitosanases can convert high molecular weight chitosan into functional chitooligosaccharides with low molecular weight. In recent years, remarkable progress has been made in the research on chitosanases. This review summarizes and discusses its biochemical properties, crystal structures, catalytic mechanisms, and protein engineering, highlighting the preparation of pure chitooligosaccharides by enzymatic hydrolysis. This review may advance the understandings on the mechanism of chitosanases and promote its industrial applications.
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Chitosan/chemistry , Chitin , Glycoside Hydrolases/genetics , Protein Engineering , Oligosaccharides/chemistry , Hydrolysisالملخص
Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.
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Objective:To evaluate the shoulder arthroscopic treatment of avulsion fracture of humeral greater tuberosity with double-row suture bridge.Methods:Retrospectively analyzed were the 13 avulsion fractures of humeral greater tuberosity which had been treated by shoulder arthroscopic double-row suture bridge at Bone and Joint Department, Guangzhou Liwan District Orthopedic Hospital from March, 2018 to March, 2020. There were 6 males and 7 females, with an average ages of 52.3 years (from 35 to 69 years). According to the Mutch classification, all the fractures of humeral greater tuberosity were attributed to the avulsion type. Of them, 3 were simple avulsion fractures of humeral greater tuberosity and 10 were complicated with shoulder anterior dislocation which was reduced manually before operation. There were 3 obsolete avulsion fractures of humeral greater tuberosity. Regular clinic and X-ray follow-ups were carried out. At the final follow-up, the pain, range of motion (ROM) and stability of the shoulder joint were assessed using visual analogue scale (VAS), American shoulder elbow scores (ASES), and Korean shoulder scores (KSS).Results:All the patients were followed up for an average of 12.3 months (from 10 to 16 months) postoperatively. No infection or shoulder instability was observed. At the final follow-up, the abduction and elevation averaged 164.6° (from 135° to 180°), the lateral external rotation 62.7° (from 40° to 80°), the internal rotation touch back test T10 level (from L2 to T6), the VAS 0.65 (from 0 to 2.5), the ASES 90.5 (from 78 to 100), and the KSS 91.5 (from 84 to 100).Conclusion:Shoulder arthroscopic treatment of avulsion fracture of humeral greater tuberosity with double-row suture bridge is minimally invasive and allows for repair of combined injury, leading to quick postoperative recovery.
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Objective:To explore the clinical efficacy of a retrograde pubic ramus intramedullary nail (RPRIN) in the treatment of anterior pelvic ring fractures.Methods:A retrospective study was conducted to analyze the 14 patients with anterior pelvic ring fracture who had been treated and followed up at Department of Traumatic Surgery, Tongji Hospital From June 2020 to February 2021. There were 10 males and 4 females with an age of (44.8±12.5) years. By the AO/OTA classification for pelvic fractures, 5 cases were type 61-A, 4 cases 61-B, and 5 cases type 61-C; by the Nakatani classification, 1 case belonged to unilateral zone Ⅰ fracture, 5 cases to unilateral zone Ⅱ fracture, 2 cases to unilateral zone Ⅲ fracture, 3 cases to right zone Ⅱ and left zone Ⅲ fracture, 2 cases to zone Ⅲ fracture on both left and right sides, and 1 case to zone Ⅱ fracture on both sides. The time from injury to operation was (7.8±1.8) days. All the anterior pelvic ring fractures were fixated with a RPRIN. The time and fluoroscopic frequency for placement of every single RPRIN, quality of fracture reduction, and pelvic function and incidence of postoperative complications at the last follow-up were recorded.Results:A total of 18 RPRINs were placed in the 14 patients. For placement of each RPRIN, the time was (35.9±8.6) min, and the fluoroscopic frequency (22.8±1.9) times. No complications such as infection occurred at any surgical incision after RPRIN placement. According to the Matta scoring, the quality of postoperative fracture reduction was assessed as excellent in 7 cases, as good in 5 cases and as fair in 2 cases. The 14 patients were followed up for (18.1+1.5) months. Their X-ray and CT images of the pelvis at the last follow-up showed that the fractures healed well and the intramedullary nails were placed in the cortical bone of the anterior ring of the pelvis. According to the Majeed scoring at the last follow-up, the pelvic function was assessed as excellent in 10 cases, as good in 3 cases and as fair in 1 case. One patient reported discomfort during squatting 2 months after operation but the symptom improved 3 months later without any special treatment. No patient experienced such complications as displacement or slippage of RPRIN, or pain at the insertion site.Conclusion:RPRIN is effective in the treatment of anterior pelvic ring fractures, showing advantages of small surgical incision, limited intraoperative fluoroscopy and short operation time.
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Objective:To report the application of our self-made Kirschner wire connecting rod combined with a conventional intramedullary nail extractor in difficult extraction of intramedullary devices.Methods:From January 2012 to August 2017, 10 patients with a hard-to-remove intramedullary device were treated at Department of Orthopaedics, The Fifth Hospital Affiliated to Xinjiang Medical University. They were 7 males and 3 females with a mean age of (40.0±9.0) years. In cases where no relevant extractor was available for the intramedullary device or it was impossible to connect the extractor connecting rod to the tail of the intramedullary device, the Kirschner wire was bent and pulled through the screw hole or the hole newly drilled at the tail of the intramedullary device to be tied or fixed with a conventional extractor connecting rod to form an effective connection. Next, our self-made Kirschner wire connecting rod was used to pull out the intramedullary device. In this cohort, 7 intramedullary nails in the tibia, 1 femoral intramedullary nail, 1 humeral intramedullary nail, and 1 tibial elastic nail were removed. The difficult extraction was due to "cold welding" of the tail cap of the intramedullary nail in 3 cases, mismatch between the screw rod of the extractor and the tail screw hole of the intramedullary nail in 4 cases, and unavailability of relevant removal tools in 3 cases. The time for intramedullary device removal, blood loss and postoperative adverse reactions were recorded.Results:Of this cohort, 9 patients underwent simple removal of the intramedullary device and 1 patient replacement of the intramedullary device. The total time for removal of an intramedullary device was (2.3±0.8) h, ranging from 1.0 to 3.2 h. The amount of blood loss was (159.0±61.0) mL, ranging from 80 to 250 mL. The follow-up was (14.5±2.2) months, ranging from 11 to 18 months. There was no infection or fracture associated with implant removal.Conclusion:Application of our self-made Kirschner wire connecting rod in combination with a conventional intramedullary nail extractor is an easy operation to successfully extract hard-to-remove intramedullary implants, requiring no more special instruments.
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Oxidative stress is a state of redox imbalance, and it easily leads to oxidative damage in an organism. The main mechanism of oxidative stress is to regulate the redox balance by activating the antioxidant system. As an important signaling molecule, hydrogen sulfide(H
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OBJECTIVE@#To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC).@*METHODS@#We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments.@*RESULTS@#MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05).@*CONCLUSION@#MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.
الموضوعات
Humans , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cyclin D1/genetics , Kidney Neoplasms/metabolism , MicroRNAs/metabolismالملخص
Objective:To investigate the inhibitory effect and underlying mechanism of gamma-secretase inhibitor blocking Notch1 signaling on retinal neovascularization caused by oxygen-induced retinopathy (OIR) in mice.Methods:To establish the OIR model, 7-day-old pups of C57BL/6J mice were exposed to 75% oxygen together with their mother until postnatal day (P)12.On P12, the mice were transferred to room air.All the mice were randomly divided into three groups, OIR group as control group, OIR+ DAPT group and OIR+ DMSO group receiving 1 μl intravitreal injection of gamma-secretase inhibitor (DAPT, 10 mmol/L) and 1∶20 DMSO dilution respectively.The right eye was taken as experimental eye.The mice were euthanized on P17 and the eyes were harvested to obtain retinas for further investigation.The total proteins were extracted from the retinas.The relative expression levels of Notch1 signal pathway and its downstream Hes1, the markers of M1 phenotype inducible nitric oxide synthase (iNOS) and M2 phenotype arginase-1 (Arg-1) microglia were measured by western blot.Retinal flat mounts were made and the retinal vessels were stained with isolectin B4 (IB4) to investigate the relative retinal neovascularization areas which was calculated as the ratio of neovascularization area/retinal area.The mumber of the neovascular endothelium cells beyond the inner limiting membrane was observed by hematoxylin-eosin staining.The use and care of animals complied with ARVO statement.This study protocol was approved by the Animal Ethics Committee of Guangdong Provincial People's Hospital (No.KY-Z-2021-2015-01).Results:The relative protein expression levels of Notch1 and Hes1 in OIR+ DAPT group, OIR group, and OIR+ DMSO group were 0.68±0.06 and 0.70±0.08, 1.00±0.00 and 1.00±0.00, 1.03±0.08 and 1.02±0.07, respectively, with statistically significant differences among them ( F=70.62, 53.65; both at P<0.01). Compared with the OIR group and OIR+ DMSO group, the expressions of Notch1 and Hes1 were significantly reduced in OIR+ DAPT group (all at P<0.01). The relative protein expression levels of iNOS and Arg-1 in OIR+ DAPT group, OIR group, and OIR+ DMSO group were 0.74±0.07 and 1.49±0.12, 1.00±0.00 and 1.00±0.00, 1.04±0.10 and 0.94±0.07, respectively, showing statistically significant differences ( F=31.63, 89.32; both at P<0.01). Compared with OIR group and OIR+ DMSO group, the expression of iNOS in OIR+ DAPT group was significantly reduced, and the expression of Arg-1 was significantly increased (all at P<0.01). The relative neovascularization area and the number of neovascular endothelium cells beyond the inner limiting membrane in OIR+ DAPT group, OIR group, and OIR+ DMSO group were (8.82±2.71)% and 38.17±3.29, (22.32±5.34)% and 60.83±5.11, (20.27±3.36)% and 58.67±4.75, respectively, showing statistically significant differences ( F=33.72, 39.44; both at P<0.01). The relative neovascularization area and the number of neovascular endothelium cells in OIR+ DAPT group were significantly reduced in comparison with OIR group and OIR+ DMSO group (all at P<0.01). Conclusions:Intravitreal injection of DAPT can inhibit the retinal neovascularization in OIR mice through blocking Notch1 signaling activation and promoting retinal microglia polarization from M1 to M2 phenotype.
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Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.
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The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.
الموضوعات
Animals , Mice , Diet, High-Fat/adverse effects , Lipid Metabolism , Cytochrome P-450 CYP1A2/pharmacology , Multiomics , Liver , Lipids/pharmacology , Tretinoin/pharmacology , Mice, Inbred C57BLالملخص
Objective:To investigate the clinical therapy of sacral osteotomy combined with lumbopelvic distraction triangular osteosynthesis for malunion and nonunion of type C longitudinally displaced sacral fracture.Methods:A retrospective study of 9 patients with malunion and nonunion of type C pelvic fractures who had been treated with sacral osteotomy combined with triangular osteosynthesis from April 2015 to January 2020 were analyzed. They were 5 men and 4 women, with an average age of 30.67±10.06 (range 14-45 years). AO/OTA classification at initial pelvic fracture, 8 cases were type C1.3 and one was type C3.3. The period from injury to surgery was 12.8±18.92 months (range 3-60 months). The cranial displacement of one side of the pelvis was 3.8±0.57 cm (range 2.5-4.1 cm). Sacral osteotomy and triangular osteosynthesis were used in all nine patients, combined with osteotomy or no osteotomy of the superior and inferior branches of the anterior ring pubis. The degree of longitudinal displacement of one side of the pelvis was assessed by making a vertical line gap between the acetabular apex on both sides and the central axis of the sacrum on the X-ray of the pelvis. The Majeed scoring and visual analogue scale (VAS) were evaluated preoperatively and at the last follow-up to assess the therapeutic effect of the patients.Results:In all 9 patients, except for 1 case of postoperative pelvic residual displacement 1.5 cm (preoperative 3.2 cm difference compared with the healthy side), the other 8 patients had a postoperative bilateral difference of 0.1-0.7 cm. All the patients were followed up for 12.00±9.95 months. At the last follow-up, the Majeed score of pelvic fracture increased from 44.0(33.5, 76.0) points preoperatively to 91.0(80.5, 92.5) points. The difference before and after operation was statistically significant ( Z=2.67, P<0.001), and the gait was significantly improved. And the VAS score for pain decreased from 6.00±1.41 points preoperatively to 1.22±0.97 points. The difference before and after operation was statistically significant ( t=8.73, P<0.001). None had complications like infection, plate broken, screw loosening, iatrogenic nerve or blood vessel injury, etc. Conclusion:Sacral osteotomy combined with lumbopelvic distraction triangular osteosynthesis for the treatment of pelvic malunion and nonunion caused by sacral fracture can correct pelvic deformity, prolong limb length, and reconstruct the stability of pelvic ring with good clinical results.
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For a long time, the cultivation of medical students’ scientific research and innovation abilitymainly depends on scattered extracurricular scientific research activities. With limited students, unsystematic teaching and inadequate administrative guarantee, it often results in obvious weakness andinefficiency. Since 2002, the Biochemistry and Molecular Biology teaching team in Shantou UniversityMedical College has been working on a “3+X” model to nurture the scientific research and innovationability of medical students. Guided by the concepts of complementary development of science andeducation, student-centeredness, and Problem-based Learning, a model is established based on the‘HEART” professionalism courses and the academy culture specific to Shantou University. We also takefull advantage of the first-tier disciplines of biology, basic medicine and clinical medicine in ShantouUniversity and collaborate with other professional teaching teams. It is conceptualized in a framework thatembraces the comprehensive connotation of scientific research and innovation ability and adopts a corecurriculum system that runs through the 5-year medical undergraduate education. In this model, " 3" means " whole-person training", " whole-process training" and " omni-directional training" for medicalstudents; " X" refers to several confirmatory dimensions of the operational effectiveness of the " 3+X" model, including organizing medical students to participate in various forms of national college students’ innovative experimental research competitions, international college students’ academic seminars, writingand publishing academic papers by medical undergraduates as the first author, etc. The model proves tobe effective in cultivating the scientific research and innovation ability of medical students, hence settinga good example to solve the current problems in the cultivation of medical students’ scientific researchand innovation ability.
الملخص
Objective:To explore the MRI features of cerebral amyloid angiopathy-related inflammation (CAA-ri).Methods:The clinical and imaging data of 12 patients with CAA-ri diagnosed in Affiliated Guizhou Aviation Industry Cor Ltd No 300 Hospital of Zunyi Medical University (9 cases), Xingyi People′s Hospital (2 cases) and Anshun people′s Hospital (1 case) from June 2013 to June 2020 were analyzed retrospectively. There were 3 females and 9 males, aged from 57 to 89 years old, with an average age of 71±10 years. The twelve patients included 5 cases with probable CAA-ri and 7 cases with possible CAA-ri. The duration of the disease ranged from 30 minutes to 2 years. One patient has ApoE ε4/ε4 gene overexpressed. All the 12 patients underwent MRI, including susceptibility weighted imaging in 12 cases, DWI in 10 cases, contrast enhanced MRI (CE-MRI) in 9 cases, MRS in 3 cases, MRA in 7 cases, and perfusion-weighted imaging in 1 case.Results:Imaging features of CAA-ri included encephalopathic, tumoral, classical cerebral amyloid angiopathy(CAA) manifestations. Twelve cases of encephalopathic manifestations showed patchy white matter hyperintensity (WMH) involving U-shaped fibers on T 2 weighted fluid-attenuated inversion recovery sequence (FLAIR), usually asymmetric,with various degree of mass effect, no diffusion restriction on DWI and no enhancement on CE-MRI. One case showed a single tumoral lesion with irregular enhancement on CE-MRI. The classic CAA findings included hemorrhagic lesions (microhemorrhage in 8 cases, lobar hemorrhage in 6 cases, subarachnoid hemorrhage in 3 cases, iron deposition on the brain surface in 7 cases) and ischemic lesions (microinfarction in 1 case, enlarged perivascular space and interlobar space in 4 cases). Follow-up showed lesions absorption and/or new lesion formation in 5 cases. Conclusions:The MRI features of CAA-ri are mainly patchy WMH involving U-shaped fibers on T 2 FLAIR, usually asymmetric, with wandering and alternating features, and inconsistency with clinical manifestations.