Objective The biomechanical performance of Ilizarov fixator models with different configurations for humeral shaft defect was compared,so as to provide a biomechanical basis for selecting the appropriate circular external fixation structure for the clinical treatment of humeral shaft defects using Ilizarov technology.Methods Based on CT data of the humerus from a healthy volunteer,the external fixators with three configurations,namely,hybrid frame,semi-ring frame and 90° fan frame were established.The finite element method was used to simulate the displacement and stress distribution under different loading conditions,and the finite element results were validated by biomechanical tests.Results Finite element analysis results:in terms of displacement,under compression,tensile and torque conditions,the displacement of 90° fan model was smaller than that of hybrid and semi-ring models.In terms of stress,the 90° fan model had the smallest displacement under tensile condition.In compression and torque tests,the semi-annular model had the lowest stress.Biomechanical test results:the semi-ring model exhibited the smallest displacement under axial compression,but there was no significant difference between the three models(P＞0.05).Conclusions The semi-ring and 90° fan frames can achieve a similar stability as the traditional hybrid frame through the strategy of'reducing the ring and increasing the stem'.The unilateral structure of the 90° fan frame has the advantages of small size,light weight,and structural stability,as well as a small impact on the shoulder and elbow joints,which makes it more valuable in clinical applications.

Objective The biomechanical performance of Ilizarov fixator models with different configurations for humeral shaft defect was compared,so as to provide a biomechanical basis for selecting the appropriate circular external fixation structure for the clinical treatment of humeral shaft defects using Ilizarov technology.Methods Based on CT data of the humerus from a healthy volunteer,the external fixators with three configurations,namely,hybrid frame,semi-ring frame and 90° fan frame were established.The finite element method was used to simulate the displacement and stress distribution under different loading conditions,and the finite element results were validated by biomechanical tests.Results Finite element analysis results:in terms of displacement,under compression,tensile and torque conditions,the displacement of 90° fan model was smaller than that of hybrid and semi-ring models.In terms of stress,the 90° fan model had the smallest displacement under tensile condition.In compression and torque tests,the semi-annular model had the lowest stress.Biomechanical test results:the semi-ring model exhibited the smallest displacement under axial compression,but there was no significant difference between the three models(P＞0.05).Conclusions The semi-ring and 90° fan frames can achieve a similar stability as the traditional hybrid frame through the strategy of'reducing the ring and increasing the stem'.The unilateral structure of the 90° fan frame has the advantages of small size,light weight,and structural stability,as well as a small impact on the shoulder and elbow joints,which makes it more valuable in clinical applications.

ObjectiveTo investigate the performance of fibrosis-4 （FIB-4） versus aspartate aminotransferase-to-platelet ratio index （APRI） in predicting advanced liver fibrosis and disease progression in patients with chronic HBV infection. MethodsA total of 497 patients with chronic HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from February 2013 to December 2022 were enrolled， among whom 404 were enrolled in a retrospective study and 75 were enrolled in a prospective study. Related indicators were collected， including demographic features （sex and age）， biochemical indices （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］）， and platelet count， and FIB-4 and APRI were calculated. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess the ability of APRI and FIB-4 in evaluating liver fibrosis degree and disease progression in patients with chronic HBV infection. ResultsIn the retrospective analysis， compared with the FIB-4<2.67 group， the FIB-4≥2.67 group had a significantly higher proportion of the patients who were diagnosed with liver cirrhosis or hepatocellular carcinoma （66.19% vs 47.54%， χ²=12.75， P<0.001）. The medians of FIB-4 and APRI increased significantly with liver fibrosis degree from F0 to F4 （H=42.5 and 35.9， both P<0.001）. As for the fibrosis stage of F0-F4， the median of FIB-4 was significantly higher than that of APRI in the patients with the same fibrosis stage （H=59.71， P<0.001）. FIB-4 and APRI had a similar AUC for predicting stage F3 fibrosis （0.67 vs 0.65， Z=0.71， P=0.480）， while FIB-4 had a higher AUC for predicting stage F4 fibrosis than APRI （0.72 vs 0.64， Z=10.50， P<0.001）. In the prospective study cohort， FIB-4 and APRI showed an increasing trend over time in predicting disease progression （chronic hepatitis B to liver cirrhosis）， with an AUC of 0.718 （95% confidence interval ［CI］： 0.476‍ ‍—‍ ‍0.760） and 0.555 （95%CI： 0.408‍ ‍—‍ ‍0.703）， respectively， and FIB-4 had a significantly higher accuracy than APRI in predicting disease progression （χ²=12.44， P<0.001）. ConclusionFIB-4 and APRI can be used to evaluate advanced liver fibrosis （F3 and F4） and predict disease progression， and FIB-4 is superior to APRI in certain aspects.

Abstract: Objective　To investigate the effect of Aedes albopictus salivary protein rAlb-34k2-1-induced mouse splenocytes immune response on dengue virus type 2 (DENV-2)-infected bone marrow-derived macrophages (BMDM) in vitro. Methods　The specific cell proliferation response of splenic cells from immunized/non-immunized mice to Alb34k2-1 protein was analyzed using the CCK-8 assay. The antigen-presenting cells (APCs) loaded with mosquito saliva proteins rAlb-34k2-1 protein/rAalb_CTL1 protein were prepared and co-cultured with lymphocytes from spleens of immunized/non-immunized mice. On the one hand, the levels of DENV-2 nucleic acids in BMDM treated with cell supernatants from mixed lymphocyte co-cultures were analyzed by qRT-PCR, and the effect of specific T cell response induced by rAlb-34k2-1 on DENV-2 replication in BMDM was analyzed. On the other hand, the expression of the DENV-2 E gene in BMDM pretreated with rAlb-34k2-1 protein was also evaluated to determine the direct effect of immunized mouse spleen lymphocytes co-cultured at 48 h and 72 h and the effect of spleen lymphocytes from immunized or non-immunized mice on DENV-2 replication in pretreated BMDMs was analyzed. Results　Compared to the non-immunized group, the rAlb-34k2-1 protein in vitro caused a specific proliferation of immunized-splenocytes, with a proliferation index (SI) >2 (P<0.000 1).Mixed lymphocyte culture supernatants loaded with rAlb-34k2-1 protein inhibited DENV-2 replication in BMDM, while the mixed lymphocyte culture supernatants loaded with rAalb_CTL1 protein had no such effect (2-ΔΔCT<0.5, P<0.05). There was no difference in DENV-2 intracellular replication in rAlb-34k2-1 pretreated BMDM after co-culture with either immunized-lymphocytes or non-immunized-lymphocytes. Conclusions　The supernatant induced by the mouse T cell response to the rAlb-34k2-1 protein can inhibit DENV-2 replication in BMDM cells, providing preliminary experimental evidence to explore the role of mosquito salivary protein-induced immune responses in the pathogenesis of mosquito-borne viruses.

Objective:To investigate the impact of exogenous lactate on the replication of dengue virus type 2 (DENV-2) in Raw264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and THP-1 cells and explore its association with cell activation.Methods:BMDMs from BALB/c mouse bone marrow were prepared and evaluated by flow cytometry to detect the proportion of F4/80 + CD11b + cells. Glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), and monocarboxylate transporters 4 (MCT4) expression at mRNA level in BMDMs at different time points after DENV-2 infection were measured by qRT-PCR. The content of lactate in the culture supernatants was quantified via colorimetric assay. CCK-8 assay was used to evaluate the impacts of different concentrations of lactate on the viability of Raw264.7 cells, BMDMs, and THP-1 cells. qRT-PCR was used to detect the expression of DENV-2 E gene, TGF-β, CD86, retinoic acid-inducible gene Ⅰ (RIG-Ⅰ), IFN-β, interferon-stimulated gene 15 (ISG15), and ISG56 at mRNA level in cells infected with DENV-2 at different MOIs in the presence of different concentrations of lactate. Meanwhile, flow cytometry was used to analyze the expression of CD86 and CD206. Results:The percentage of BMDMs was (87.53±1.66)%. GLUT1 expression at mRNA level exhibited a decrease in BMDMs at 24 h after DENV-2 (MOI=3) infection following a transient increase at 12 h ( P<0.05), while HK2 expression at mRNA level was higher that than in blank control and inactivated DENV-2 infection groups at 12, 24, and 36 h ( P<0.01). Besides, there was an increase in both MCT4 mRNA level and the content of lactate in culture supernatants at 24 h after DENV-2 (MOI=1.5) infection ( P<0.05). The viability of the three types of cells remained above 80% when the concentration of lactate was 31.25 mmol/L. Lactate at the concentration of 35 mmol/L increased the expression of the DENV E gene at mRNA level in DENV-2-infected BMDMs at MOI=1 or MOI=2 ( P<0.05). Besides, it promoted the expression of DENV E gene at mRNA level in Raw264.7 and THP-1 cells ( P<0.001) as well as the expression of CD163, TGF-β, RIG-Ⅰ, IFN-β, ISG15 and ISG56 at mRNA level in BMDMs at MOI=1.5, but inhibited the expression of CD86 at mRNA level in BMDMs ( P<0.05). It also up-regulated CD206 protein expression ( P<0.01) and down-regulated CD86 protein expression ( P>0.05) in BMDMs. Conclusions:Exogenous lactate enhances DENV-2 replication in both human- and murine-derived macrophages and that might correlate with M2 macrophage polarization.

OBJECTIVE: To analyze the risk factors of in-hospital death in patients with sepsis in the intensive care unit (ICU) based on machine learning, and to construct a predictive model, and to explore the predictive value of the predictive model. METHODS: The clinical data of patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to April 2021 were retrospectively analyzed,including demographic information, vital signs, complications, laboratory examination indicators, diagnosis, treatment, etc. Patients were divided into death group and survival group according to whether in-hospital death occurred. The cases in the dataset (70%) were randomly selected as the training set for building the model, and the remaining 30% of the cases were used as the validation set. Based on seven machine learning models including logistic regression (LR), K-nearest neighbor (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), extreme gradient boosting (XGBoost) and artificial neural network (ANN), a prediction model for in-hospital mortality of sepsis patients was constructed. The receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA) were used to evaluate the predictive performance of the seven models from the aspects of identification, calibration and clinical application, respectively. In addition, the predictive model based on machine learning was compared with the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) models. RESULTS: A total of 741 patients with sepsis were included, of which 390 were discharged after improvement, 351 died in hospital, and the in-hospital mortality was 47.4%. There were significant differences in gender, age, APACHE II score, SOFA score, Glasgow coma score (GCS), heart rate, oxygen index (PaO₂/FiO₂), mechanical ventilation ratio, mechanical ventilation time, proportion of norepinephrine (NE) used, maximum NE, lactic acid (Lac), activated partial thromboplastin time (APTT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), blood uric acid (BUA), pH value, base excess (BE), and K⁺ between the death group and the survival group. ROC curve analysis showed that the area under the curve (AUC) of RF, XGBoost, LR, ANN, DT, SVM, KNN models, SOFA score, and APACHE II score for predicting in-hospital mortality of sepsis patients were 0.871, 0.846, 0.751, 0.747, 0.677, 0.657, 0.555, 0.749 and 0.760, respectively. Among all the models, the RF model had the highest precision (0.750), accuracy (0.785), recall (0.773), and F1 score (0.761), and best discrimination. The calibration curve showed that the RF model performed best among the seven machine learning models. DCA curve showed that the RF model exhibited greater net benefit as well as threshold probability compared to other models, indicating that the RF model was the best model with good clinical utility. CONCLUSIONS The machine learning model can be used as a reliable tool for predicting in-hospital mortality in sepsis patients. RF models has the best predictive performance, which is helpful for clinicians to identify high-risk patients and implement early intervention to reduce mortality.
Humans ; Hospital Mortality ; Retrospective Studies ; ROC Curve ; Prognosis ; Sepsis/diagnosis* ; Intensive Care Units

Objective:To construct a nomogram model predicting the occurrence of acute kidney injury (AKI) in patients with sepsis in the intensive care unit (ICU), and to verify its validity for early prediction.Methods:Sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to December 2021 were retrospectively included, and those who met the inclusion criteria were randomly divided into training and validation sets at a ratio of 7:3. Univariate and multivariate logistic regression models were used to identify independent risk factors for AKI in patients with sepsis, and a nomogram was constructed based on the independent risk factors. Calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the nomogram model.Results:741 patients with sepsis were included in the study, 335 patients developed AKI within 7 d of ICU admission, with an AKI incidence of 45.1%. Randomization was performed in the training set ( n=519) and internal validation set ( n=222). Multivariate logistic analysis revealed that acute physiology and chronic health status score Ⅱ, sequential organ failure score, serum lactate, calcitoninogen, norepinephrine dose, urea nitrogen, and neutrophil percentage were independent factors influencing the occurrence of AKI, and a nomogram model was constructed by combining these variables. In the training set, the AUC of the nomogram model ROC was 0.875 (95% CI: 0.767-0.835), the calibration curve showed consistency between the predicted and actual probabilities, and the DCA showed a good net clinical benefit. In the internal validation set, the nomogram model had a similar predictive value for AKI (AUC=0.871, 95% CI: 0.734-0.854). Conclusions:A nomogram model constructed based on the critical care score at admission combined with inflammatory markers can be used for the early prediction of AKI in sepsis patients in the ICU. The model is helpful for clinicians early identify AKI in sepsis patients.

Objective:To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Five UESL cases operated on at Hunan Provincial People's Hospital from 2014 to 2021 were retrospectively analyzed. H&E and immunohistochemical staining were done for pathological observation.Results:The 5 UESL patients(two boys,three girls) were 0.5 to 15 years old, all underwent radical surgical resection. In 3 cases tumors located in right liver, 1 in left liver, 1 in both lobes. Radiographically and visually, the tumor is a large cystic solid mass, microscopically composed of myxoid stroma and undifferentiated stromal cells, with pleomorphic tumor giant cells and characteristic eosinophilic bodies. All 5 patients are now alive after surgical resection: 1 patient achieved disease-free survival of more than 91 months after surgery alone. Two patients had recurrence after surgery and received surgical resection plus chemotherapy or chemotherapy alone. They achieved survival of more than 35 and 16 months, respectively. Two patients were treated with chemotherapy or chemotherapy plus radiotherapy after surgery and survived more than 49 and 31 months without recurrence, respectively.Conclusions:UESL is a rare and highly malignant mesenchymal tumor with characteristic pathologic morphology. Radical resection is the key to the treatment for UESL, and chemotherapy and radiotherapy should be carried out after surgery.

Objective:To investigate the value of ultrasound in the diagnosis of secondary loss of response in children with Crohn′s disease at maintenance stage treated with Infliximab.Methods:From January 2017 to December 2021, 51 children with Crohn′s disease who received Infliximab treatment and clinical response in the Beijing Children′s Hospital Affiliated to Capital Medical University were retrospectively analyzed, and whether there was secondary loss of response during the maintenance period was observed. The ultrasound examination results at the 14th week of treatment were collected to understand the correlation between ultrasound examination of intestinal wall and peri-intestinal healing and secondary loss of response.Results:A total of 15 out of 51 patients (29.4%) experienced secondary loss of response during treatment follow-up up to 54 weeks. Compared to children with continuous response, children with secondary loss of response had a thicker intestinal wall at week 14 of treatment [5.0 (3.8, 6.0)mm compared to 3.0 (2.0, 4.0)mm, P<0.001], and a higher proportion of intestinal wall stratified structure disappearance [8/15 (53.33%) compared to 3/36 (8.33%), P<0.001]. When intestinal wall thickness>3.0 mm, the sensitivity was 0.955, and the specificity was 0.483. The sensitivity and specificity of clear diagnosis of secondary loss of response in intestinal wall stratification were 0.727 and 0.825, respectively. The sensitivity and specificity of combined diagnosis for secondary loss of response were 0.933 and 0.611, respectively. Conclusions:At the 14th week of treatment with Infliximab in children with Crohn′s disease, the thickness of intestinal wall measured by ultrasound being more than 3.0 mm and the disappearance of intestinal wall statified structure provide important information for the diagnosis of secondary loss of response.

Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited childhood white-matter disorders, and the pathogenic gene has been confirmed as EIF2B gene. VWM is characterized by chronic progressive neurological deterioration with cerebellar ataxia, usually less prominent spasticity and relatively mild mental decline. There are episodes of rapid and major neurological deterioration provoked by stresses, such as fever, minor physical trauma and acute fright, which is a characteristic clinical feature of VWM. Brain magnetic resonance imaging findings are diagnostic in almost all patients,and the disappearance of the cerebral white matter occurs in a diffuse "melting away" pattern. The onset of VWM can be at any age from fetal stage to adult stage, and the clinical phenotypes vary immensely. Gene diagnosis is the golden standard for VWM. This article reported a patient with a course of 17 years, who was misdiagnosed as Wilson′s disease because of low serum ceruloplasmin, and was finally diagnosed as VWM by reinterpretation of whole exome sequencing, which is worthy of clinicians′ vigilance and consideration.