BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

BACKGROUND:The occurrence and development of osteoarthritis is strongly associated with immune abnormalities,and the importance of various immune cells and immune mediators in the pathogenesis of osteoarthritis has been continuously elucidated. OBJECTIVE:To review the role of immune cells and related cytokines in osteoarthritis disease,and provide new ideas for future research and prevention of osteoarthritis. METHODS:Taking"osteoarthritis,knee,macrophages,T cells,B cells,natural killer cells,dendritic cells,cytokines,inflammatory factors,immune cells"as search terms,relevant published literature was searched on CNKI,WanFang,VIP,PubMed and Web of Science databases.After reading the title and abstract for preliminary screening,98 articles were selected for review after reading the full text again. RESULTS AND CONCLUSION:In the past,it was believed that the pathogenesis of osteoarthritis was associated with cartilage wear.In recent years,studies have suggested that osteoarthritis is a chronic inflammatory state in which immune cells are widely involved.With the in-depth study of the pathogenesis of osteoarthritis,scholars believe that the pathogenesis of osteoarthritis is driven by early innate immune response,which will gradually catalyze degenerative changes and eventually lead to changes in the joint microenvironment.Various immune cells and cytokines are the key factors affecting the repair of osteoarthritis.Macrophages and natural killer cells participate in synovial inflammatory reaction,and T cell immune reaction participates in the degradation of osteoarthritis cartilage and aggravates the condition of osteoarthritis.Interleukin-1β secreted by immune cells,interleukin-6,tumor necrosis factor α,interleukin-17 and interleukin-37 play an important role in the pathophysiology of osteoarthritis,among which interleukin-1β is the most important inflammatory factor causing articular cartilage damage.Assessing immunological risk factors at the early stage of osteoarthritis can effectively treat the disease at an early stage,which can significantly reduce disability,morbidity and costs associated with osteoarthritis.At present,the immunomodulatory effect of stem cells and their derived secretions and biomaterials on the treatment of osteoarthritis has been confirmed in different experimental models,but there is still a lot of research to be done before they are used in clinical practice.With the discovery of new therapeutic targets,targeted treatment will bring new hope for the repair of clinical osteoarthritis.

Abernethy malformation， also known as congenital portosystemic shunts， is rare in clinical practice， with less than 300 cases reported in the global literature up to 2019. The disease can have serious complications such as pulmonary hypertension， liver tumor， and liver failure and tends to have an extremely poor prognosis， and early diagnosis and active and effective treatment can reduce and delay the onset of complications. In this case， portography combined with balloon occlusion helped to display the underdeveloped slender portal vein with dysplasia， so that the child who was formerly misdiagnosed with type Ⅰ Abernethy malformation was diagnosed with type Ⅱ Abernethy malformation， and then the child was successfully treated by transcatheter closure. This article gives a detailed report of this case.

Objective:To construct an intelligent foreign bodies detection model based on Faster R-convolutional neural network in posterior-anterior chest X-ray and evaluate the performance of the model.Methods:Totally 5 567 adult posterior-anterior DR chest radiographs from Zhejiang Provincial People′s Hospital and Chun′an County People′s Hospital from June 2019 to March 2020, with 4 247 foreign body-containing chest radiographs were analyzed retrospectively. All data were randomly divided into training set (2 911 foreign body-containing), validation set ( n=1 456, 733 foreign body-containing, 723 free of foreign body) and testing set ( n=1 200, 603 foreign body-containing, 597 free of foreign body). The reference gold standard was set as the results of each chest radiography with foreign body annotated by two radiology residents and reviewed and corrected by a senior radiographer. The receiver operating characteristic (ROC) curve and the area under the curve were used to analyze the efficiency of the deep learning model to distinguish the presence or absence of foreign bodies on chest radiography in the testing set. The precision-recall curve and mean precision (mAP) were used to analyze the stability of the model at different levels. Finally, the influence of different locations, patient gender, and patient age on the foreign body recall of the deep learning model were analyzed. Results:In the testing set, the sensitivity of the deep learning model in diagnosing whether chest radiograph contained foreign bodies was 93.2%(562/603), the specificity was 92.6%(553/597), and the F1 score was 0.94. The area under the ROC curve was 0.97, and the mAP value was 0.69. For foreign bodies in different locations, the recall rates of foreign bodies in lung field and outside lung field were 91.2% (674/739) and 89.0% (1 411/1 585), respectively. For different genders, the recall rates for male and female foreign body detection were 87.3% (337/386) and 90.0%(1 745/1 938), respectively. For different age ranges, the recall rate of foreign body detection was 92.5% (1 041/1 126) for 18-38 years old, 89.7%(505/563) for 39-58 years old, 83.5%(335/401) for 59-78 years old and 85.9% (201/234) for patients ≥79 years old.Conclusion:The constructed deep learning-based foreign body detection model for adult posterior-anterior chest X-ray provides high sensitivity and stability, which can identify foreign bodies in chest radiography quickly and accurately.

Objective:To Eveluate the safty and clinical efficacy of combined laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation in the treatment of solid pseudopapillary neoplasm.Methods:A 22 years old solid pseudopapillary neoplasm female patient who underwent distal pancreatectomy and an autologous islet transplantation at Tianjin First Central Hospital, clinical date for 6 months follow up was collected and analyzed.Results:The patient was well recovered after surgery, and during the post-operative follow up, the fasting blood glucose was 5.72 mmol/L, HbA1c was 6.1%, remained insulin independent, the liver function was kept well.Conclusions:Combined Laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation can effectively prevent diabetes after distal pancreatectomy.

Objective:The vasculature and canal were located using radiography after the fresh osseous specimens were decalcified, after which the anatomic investigation of intraosseous vasculature was conducted based on the orientation of the canals.Methods:To investigate the basic dissected methods for intraosseous vasculature and the related clinical significance. Methods The materials were obtained from seven fresh knee joint specimens from patients with amputation due to car accidents, nine fresh knee joint specimens from patients with amputation due to oncological radical surgery, and 44 knee joint specimens from 24 cadavers. Among them, 22 were males (55%) and 18 were females (45%), 28 were left knees (46.7%) and 32 were right knees (53.3%). 10 were aged from 16-90 years old (from 8 donors) and 50 were aged from 15-85 years old (from 32 donors). The tributaries of middle genicular vein which penetrate into the proximal tibial epiphysis and metaphysis via our previously discovered and denominated "foramen of tibial intercondylar eminence (FTIE)" were dissected as an example. After obtaining the fresh knee joint specimen, angiography was performed to observe the continuous extraosseous and intraosseous blood vessels. The first group of specimens with the removal of cortical bone was reserved in formalin solution at 4 °C for 7 d, sequentially immersed in Ethylene Diamine Tetraacetic Acid (EDTA), the decalcification agent, for 30 d with replacement for each two days. Based on the CT scanning and three-dimensional reconstruction, the orientation of bony canal which enclosed the vasculature was exposed to guide the anatomic incision. The exquisite dissection was achieved with the help of ophthalmological microsurgical instruments. The anatomical dissection were intuitively observed, compared with the angiographic images, and verified by histological examinations. The second group of samples was decalcified with strong acid as another strategy, and the comparison between different groups was conducted. To estimate the advantages and disadvantages of the two decalcification and dissection methods, and the distribution and universality of specific intraosseous vasculatures and canals, the methods can be utilized to dissect the diameter of the intraosseous vessels. Based on the anatomical study of intraosseous vasculature, the mechanisms including etiology, recurrence and spread of bone tumors and epiphyseal injuries were analyzed to improve the therapeutic regimen.Results:The intraosseous tributaries of middle genicular vein which penetrate into the tibial intercondylar eminence from the articular cavity were dissected, these vessels extended to the tibial metaphysis from epiphysis through the epiphyseal line or senescent physes. The diameter of the vessel entering the FTIE was 1.2 mm, and the intraosseous vessels divided into several tinier tributaries with the diameter of 0.3 mm to cross the epiphyseal line or closed physeal plate and differentiated into capillaries in the distal regions, therefore was difficult to dissect directly. The histological examinations confirmed the authenticity of intraosseous vessels. Compared with the samples decalcified with strong acid, the blood vessels were obviously dissolved, and only a few residual epithelial cells were observed under the light microscope. Based on the anatomical study of intraosseous vessels, the treatment protocols for some related bone tumors and epiphyseal injuries were modified and satisfactory results were achieved.Conclusion:The methods can realize the ideal direct dissection for the intraosseous blood vessels with the outer diameter greater than or equal to 0.3 mm.

Objective:To investigate the complications and prevention strategies of Dynesys stabilization in the treatment of lumbar degenerative disease.Methods:Two hundred and forty-three patients underwent lumbar spine stabilization with Dynesys owing to lumbar degenerative disease were retrospectively analyzed from July 2008 to December 2016. The mean follow-up time was 5.6 years (48-148 months). There were 152 patients with lumbar disc herniation and 91 patients with lumbar spinal stenosis. 167 cases underwent single-level operation, 71 cases underwent two-level operation, and 5 cases underwent three-level operation. All patients had low back pain, radiating pain in the lower extremities, and/or intermittent claudication. Clinical outcomes were evaluated using Oswestry disability index (ODI) and visual analogue scale (VAS). The occurrence of perioperative complications (with in 3 months) and postoperative complications (after 3 months) after the operation were recorded and analyzed. Radiographic adjacent segment degeneration (ASD) was evaluate dusing University of California at Los Angeles Grading Scale (UCLA).Results:All patients underwent surgery successfully. ODI score of patients improved from 55.1%±16.8% preoperatively to 15.6%±5.8% at the final follow-up, the difference was statistically significant ( t=34.6, P<0.01). VAS score decreased from 6.4±2.3 preoperatively to 1.1±0.4 at the final follow-up, the difference was also statistically significant ( t=35.4, P<0.01). There were 25 cases (10.29%) with complications, and 3 cases (1.23%) underwent secondary operation. Perioperative complications occurred in 13 patients (5.35%), including 5 cases of cerebros pinal fluid leakage, 5 cases of poor wound healing (2.06%), and 3 cases of deep wound infection (1.23%). Twelve patients (4.94%) had long-term postoperative complications, including 6 patients (2.47%) of unilateral screw loosening at the 5-year follow-up, 3 patients (1.23%) of screw fracture, and 3 patients (1.23%) of symptomatic ASD, among whom 2 patients underwent secondary operation, and 1 patient underwent conservative treatment. There was no recurrence at the operated segments in all patients. At the final follow-up, 41 patients (16.87%) had radiographic ASD. The UCLA score atthe final follow-up was significantly different from that preoperatively ( Z=2.60, P=0.01). Conclusion:Dynesys dynamic system combined with decompression in the treatment of degenerative lumbar spine diseases can achieve good long-term clinical outcome, with low incidence of complications and ASD.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective To analyze the clinical,radiological features and risk factors of diplopia in patients with acute lacunar infarction (ALI).Methods Retrospectively retrieved patients of ALI (lesion diameter was less than 1.5 cm in DWI sequence)diagnosed by MR and clinical.We further summarized 13 ALI patients with diplopia and randomly selected 13 ALI patients without diplopia as the control group. SPSS22.0 statistical software was used for statistical analysis.The general clinical data such as sex and age was compared by Ch-i square test and t-test.The risk factors were primarily analyzed by one-way ANOVA and then the risk factors with statistical significance were brought into the logistic regression model for multivariate analysis.Results The incidence of diplopia in ALI patients was about 2.7%(13/489). The infarct sites were all located in the brain stem of the oculomotor-related brain nucleus and the dorsolateral medulla oblongata.Hypertension and hematocrit were negatively correlated with diplopia after infarction (P＜0.05 ).Conclusion The incidence of diplopia is low in ALI patients.The medial longitudinal tract of the dorsolateral medulla is an important area causing diplopia.Hypertension and hematocrit are non-risk factors for diplopia after ALI.