Galectin-9 alleviates acute graft-versus-host disease after haplo-hematopoietic stem cell transplantation by regulating regulatory T cell/effector T cell imbalance.

BACKGROUND: Acute graft-versus-host disease (aGVHD) arises from the imbalance of host T cells. Galectin-9 negatively regulates CD4 effector T cell (Th1 and Th17) function by binding to Tim-3. However, the relationship between Galectin-9/Tim-3 and CD4+ T subsets in patients with aGVHD after Haplo-HSCT (haploidentical peripheral blood hematopoietic stem cell transplantation) has not been fully elucidated. Here, we investigated the role of Galectin-9 and CD4+ T subsets in aGVHD after haplo-HSCT. METHODS: Forty-two patients underwent Haplo-HSCT (26 without aGVHD and 16 with aGVHD), and 20 healthy controls were included. The concentrations of Galectin-9, interferon-gamma (IFN-γ), interleukin (IL)-4, transforming growth factor (TGF)-ß, and IL-17 in the serum and culture supernatant were measured using enzyme-linked immunosorbent assay or cytometric bead array. The expression levels of Galectin-9, PI3K, p-PI3K, and p-mTOR protein were detected by western blot analysis. Flow cytometry was used to analyze the proportions of CD4+ T cell subsets. Bioinformatics analysis was performed. RESULTS: In patients with aGVHD, regulatory T (Treg) cells and Galectin-9 decreased, and the Th1, Th17, and Treg cells were significantly imbalanced. Moreover, Treg and Galectin-9 were rapidly reconstituted in the early stage of patients without aGVHD after Haplo-HSCT, but Th17 cells were reconstituted slowly. Furthermore, Tim-3 upregulation on Th17 and Th1 cells was associated with excessive activation of the PI3K/AKT pathway in patients with aGVHD. Specifically, in vitro treatment with Galectin-9 reduced IFN-γ and IL-17 production while augmenting TGF-ß secretion. Bioinformatics analysis suggested the potential involvement of the PI3K/AKT/mTOR pathway in aGVHD. Mechanistically, exogenous Galectin-9 was found to mitigate aGVHD by restoring the Treg/Teffs (effector T cells) balance and suppressing PI3K. CONCLUSION: Galectin-9 may ameliorate aGVHD after haplo-HSCT by modulating Treg/Teffs balance and regulating the PI3K/AKT/mTOR pathway. Targeting Galectin-9 may hold potential value for the treatment of aGVHD.

[Determination of boric acid and silicic acid in mineral water by nonsuppressed ion chromatography].

Boron and silicon are widely distributed in nature; in water, these compounds typically present in the forms of boric acid and silicic acid, respectively. The maximum allowable levels of silicic acid and boric acid in water are stipulated in relevant national and industry standards, such as GB 8538-2022. Quality changes in water, which are of great significance in water-quality evaluations, can be understood in terms of its silicic acid and boric acid contents. Boric acid content is usually determined by ion exclusion chromatography, whereas silicic acid content is usually determined by postcolumn derivatization. Therefore, traditional methods cannot achieve the simultaneous determination of silicic acid and boric acid contents in water. Modern ion chromatography has been widely used in the detection of ionic compounds, such as anions, cations, organic acids, organic amines, amino acids, and sugars. Boric (pKa=9.24) and silicic (pKa=9.77) acids are weak acids that dissociate into ionic states under alkaline conditions. Although these compounds cannot be tested using suppressed ion chromatography, they can be retained on ion chromatography columns. In this study, a method based on nonsuppressed conductance detection was established for the simultaneous determination of boric acid and silicic acid in water. The contents of boric acid and silicic acid were detected by nonsuppressed ion chromatography using a Dionex IonPacTM AS20 analytical column. The chromatographic conditions were as follows: flow rate, 1.0 mL/min; column temperature, 30 ℃; eluent, 6 mmol/L sodium hydroxide solution and 60 mmol/L mannitol; and sample injection volume, 50 µL. The effective separation of silicic acid and boric acid was achieved within 8 min. SiO32- and boric acid demonstrated good linear relationships in the concentration ranges of 0.25-100 and 0.5-100 mg/L (correlation coefficients, 0.9999), respectively. The method detection (MDL) and quantification (MQL) limits were 0.078 and 0.26 mg/L for SiO32-, and the MDL and MQL limits were 0.18 and 0.60 mg/L for boric acid. The average recoveries of boric acid and SiO32- (n=6) were 97.3%-105.3%. Moreover, the relative standard deviations were less than 0.9% for boric acid at four spiked levels and less than 0.30% for SiO32- at three spiked levels. Thus, the method meets detection requirements. The pretreatment method is very simple, and the sample can be directly injected through a 0.22 µm water filtration membrane and into the column. The boric acid and silicic acid contents in nine mineral drinking water samples were determined under the optimized analytical conditions. Boric acid was not detected in these nine samples, but silicic acid was detected in six samples. The silicic acid contents detected were between 18.70 and 62.08 mg/L, which was consistent with the concentration ranges marked on the manufacturers' packaging. The proposed method can be used for the determination of boric acid and silicic acid in mineral drinking water and laboratory water, and provides a reference for the simultaneous detection of boric acid and silicic acid in ultrapure water used in the semiconductor industry.

The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT.

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Leaf-Root-Soil Stoichiometric Characteristics in Different Shrub Ages of Ammopiptanthus mongolicus.

The ecological indicators for the growth and restoration of A. mongolicus populations are important for grasping the regulatory mechanisms of the biogeochemistry cycle, and for providing basic data for the prediction and evaluation of the evolution characteristics of natural A. mongolicus populations. We conducted studies on the eco-stoichiometric characteristics of natural A. mongolicus in different shrub ages, in order to understand the nutrient limitations for the growth and development of A. mongolicus and the synergy between the soil, leaves and roots, and to explore the C, N and P stoichiometric characteristics on A. mongolicus. The results showed the following: (1) The response of C, N and P stoichiometric characteristics in the leaves, roots and soil to changes in shrub age was not completely consistent. The leaf C content was young shrub> mature shrub> middle age shrub. The C content in the root system and C and N content in the soil showed an upward trend with increasing shrub age. The N and P contents of the root system and the P content of the soil showed a downward trend with increasing shrub age. The stoichiometric ratios C:N, C:P and N:P in the leaves, roots and soil showed an upward trend, and the N:P ratios in the leaves and roots were similar. (2) Among the stoichiometric characteristics of the leaves, C, N and P, leaves P and C:P are the most sensitive to shrub age changes, and have ecological implications for the growth and population dynamics of A. mongolicus. The average N:P ratios of young A. mongolicus leaves in young, middle-aged and mature shrubs were 15.32, 18.23 and 21.76, respectively. It can be seen that with an increase in shrub age, the growth of A. mongolicus gradually shifted from being jointly restricted by N and P to being more restricted by P. (3) The N content and the C∶N and N∶P ratios of A. mongolicus are classified as "strictly homoeostasis ", which shows strong plant homoeostasis for environmental adaptability. The N supplemented by symbiotic nitrogen fixation makes A. mongolicus have strong N internal homoeostasis. Therefore, in a desert grassland with low N content, the growth process of A. mongolicus may be easily restricted by P due to the additional N absorbed by it. (4) The C, N and P contents of the leaves, roots and soils of the three shrubs were shown as leaf > root > soil, and the difference was significant (p < 0.05). The correlation analysis showed that the C, N and P contents of the soil, roots and leaves and their stoichiometric ratio characteristics of the three shrubs showed a certain correlation. Among them, the P content of the soil was significantly related to the N:P ratio of the leaves and roots. Therefore, P is likely to become a limiting factor in the plant growth and repair process of the plant ecosystem in the A. mongolicus population. In summary, during the growth of A. mongolicus, special attention should be paid to the balance of nutrients. In order to improve its productivity, it is recommended to reasonably apply P fertilizers in the process of tending management to enhance the soil nutrient status and improve plant nutrient utilization efficiency and homoeostasis.

Unique Reduced-Intensity Conditioning Haploidentical Peripheral Blood Stem Cell Transplantation Protocol for Patients with Hematologic Malignancy.

Reduced-intensity conditioning (RIC) haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) requires more hematopoietic progenitor and stem cells (HPSCs) to promote engraftment and immune reconstitution and needs a stronger graft-versus-leukemia effect. Peripheral blood stem cells (PBSCs) offer advantages over bone marrow; however, the use of higher-dose non-T cell-depleted (non-TCD) in vitro PBSCs may increase the occurrence of severe graft-versus-host disease (GVHD). This prospective, single-arm clinical study was performed to investigate using high-dose non-TCD in vitro PBSCs as the graft source, using fludarabine/Ara-C/busulfan (FAB) as the conditioning regimen, using rabbit antithymocyte globulin to remove T cells in vivo, and enhancing GVHD prophylaxis with an IL-2 receptor antagonist in RIC-haplo-HSCT in patients with hematologic malignancies age 50 to 70 years or <50 years with comorbidities (Hematopoietic Cell Transplantation Comorbidity Index score ≥2) classified as intermediate to high risk. The primary endpoint was day 100 acute GVHD (aGVHD). A total of 47 patients were enrolled; the median age was 52 years (range, 30 to 68 years), the median duration of follow-up was 34 months (range, 2 to 99 months), and the medium-infused doses of mononuclear cells, CD34+ cells, and CD3+ cells were 15.93 × 108/kg, 8.68 × 106/kg, and 5.57 × 108/kg, respectively. The cumulative incidence of grade II-IV aGVHD at day 100 was 30.3% (95% confidence interval [CI], 15.9% to 44.8%), and that of grade III-IV aGVHD was 10.2% (95% CI, .6% to 19.8%). The 2-year cumulative incidence of chronic GVHD (cGVHD) was 34.9% (95% CI, 19.0% to 50.8%). The 2-year cumulative incidences of localized and extensive cGVHD were 26.1% (95% CI, 11.80% to 40.40%) and 8.7% (95% CI, 3.26% to 20.65%), respectively. The 2-year cumulative incidence of relapse was 17.3% (95% CI, 5.1% to 29.5%), the 2-year overall survival rate was 71.2% (95% CI, 57.9% to 84.5%), and the 2-year disease-free survival rate was 66.2% (95% CI, 52.1% to 80.3%). The incidence of aGVHD was not high, and the overall efficacy was good. This study demonstrates that this unique RIC-haplo-PBSC transplantation protocol was effective in treating hematologic malignancies. Nonetheless, larger prospective multicenter clinical trials and experimental studies should be performed to further confirm our findings.

Ecological Stoichiometric Characteristics in Organs of Ammopiptanthus mongolicus in Different Habitats.

The essence of plant ecological stoichiometry is to study the relationships between species and their environment, including nutrient absorption, utilization and cycling processes as well as the nutrient limitation of plants. Plants can regulate nutrient elements and adapt to environmental changes. To understand the adaptation mechanism, it is important to take plants as a whole and quantify the correlation between the chemometrics of different organs. Ammopiptanthus mongolicus is within the second-class group of rare−endangered plants in China and is the only evergreen broad-leaved shrub in desert areas. We analyzed the ecological stoichiometric characteristics of leaves, stems, roots, flowers and seeds of A. mongolicus in five habitats, namely fixed sandy land, semi-fixed sandy land, stony−sandy land, alluvial gravel slope and saline−alkali land. We found that (1) the nutrient contents of N, P and K were in the order of seed > flower > leaf > root > stem. The enrichment of the N, P and K in the reproductive organs promoted the transition from vegetative growth to reproductive growth. Additionally, (2) the contents of C, N, P and K and their stoichiometric ratios in different organs varied among different habitat types. The storage capacity of C, N and P was higher in sandy soil (fixed and semi-fixed sandy land), whereas the content of K was higher in gravelly soil (stony−sandy land and alluvial gravel slope), and the C:N, C:P and N:P were significantly higher in gravelly soil than those in sandy soil. A. mongolicus had higher nutrient use efficiency in stony−sandy land and alluvial gravel slope. Furthermore, (3) the C:N and N:P ratios in each organ were relatively stable among different habitats, whereas the K:P ratio varied greatly. The N:P ratios of leaves were all greater than 16 in different habitats, indicating that the growth was mainly limited by P. Moreover, (4) except for the P element, the content of each element and its stoichiometric ratio were affected by the interaction between organs and habitat. Habitat had a greater impact on C content, whereas organs had a greater influence on N, P and K content and C:N, C:P, C:K and N:P.

The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Prediction of acute kidney injury in patients with femoral neck fracture utilizing machine learning.

Background: Acute kidney injury (AKI) is a common complication associated with significant morbidity and mortality in high-energy trauma patients. Given the poor efficacy of interventions after AKI development, it is important to predict AKI before its diagnosis. Therefore, this study aimed to develop models using machine learning algorithms to predict the risk of AKI in patients with femoral neck fractures. Methods: We developed machine-learning models using the Medical Information Mart from Intensive Care (MIMIC)-IV database. AKI was predicted using 10 predictive models in three-time windows, 24, 48, and 72 h. Three optimal models were selected according to the accuracy and area under the receiver operating characteristic curve (AUROC), and the hyperparameters were adjusted using a random search algorithm. The Shapley additive explanation (SHAP) analysis was used to determine the impact and importance of each feature on the prediction. Compact models were developed using important features chosen based on their SHAP values and clinical availability. Finally, we evaluated the models using metrics such as accuracy, precision, AUROC, recall, F1 scores, and kappa values on the test set after hyperparameter tuning. Results: A total of 1,596 patients in MIMIC-IV were included in the final cohort, and 402 (25%) patients developed AKI after surgery. The light gradient boosting machine (LightGBM) model showed the best overall performance for predicting AKI before 24, 48, and 72 h. AUROCs were 0.929, 0.862, and 0.904. The SHAP value was used to interpret the prediction models. Renal function markers and perioperative blood transfusions are the most critical features for predicting AKI. In compact models, LightGBM still performs the best. AUROCs were 0.930, 0.859, and 0.901. Conclusions: In our analysis, we discovered that LightGBM had the best metrics among all algorithms used. Our study identified the LightGBM as a solid first-choice algorithm for early AKI prediction in patients after femoral neck fracture surgery.

A quantitative study of bone defects in displaced femoral neck fractures based on virtual reduction techniques.

BACKGROUND: Bone defects in femoral neck fractures are strongly associated with the prognosis after internal fixation. However, qualitative analysis of bone defects in femoral neck fractures has already been performed, quantitative studies have not been reported. In this study, we aimed to systematically analyse the morphological characteristics of bone defects in patients with femoral neck fractures using computed tomography (CT) images combined with computer image analysis techniques. METHODS: Four hundred and sixty-nine patients with femoral neck fractures from January 2014 to December 2018 at two grade A tertiary hospitals were included. Models were created in Mimics software based on CT images collected within 1 week after injury and then imported into 3-matic software for virtual reduction. The volume of the bone defect (VBD), maximum defect thickness (MDT), extent of the bone defect region (EBDR) , main defect quadrant (MDQ), collapse type and fracture classification were calculated and recorded. RESULTS: The EBDR, collapse type and MDT all had a significant positive effect on the VBD (P <0.05), with a more significant effect at higher quantiles. Age also had a significant positive effect on the VBD (P < 0.05), but its effect was more pronounced at lower quantiles. Compared to non-subcapital fractures, subcapital fractures had a positive effect on the VBD only at the 50 and 75% quantiles (P < 0.01). The female sex had a significant negative effect on the VBD compared to the male sex (P < 0.05). CONCLUSION: This study established a reliable computer image processing method for quantitative analysis of the VBD in femoral neck fractures and revealed that all patients with femoral neck fractures had bone defects, which can occur at any part of the femoral neck. The EBDR, MDT, collapse type, and patient age and sex were all important risk factors for the extent of the defect and should be taken into account in surgical planning.

[Femoral head necrosis rate and risk factors after internal fixation of femoral neck fracture:a Meta-analysis].

OBJECTIVE: To study the incidence and risk factors of osteonecrosis of the femoral head (ONFH) after internal fixation in adult patients with femoral neck fracture (FNF) after 2000, and identify high-risk population of ONFH. METHODS: PubMed, Medline, The Cochrane Library, CNKI, Wanfang and VIP Database were searched to collect all the literatures on ONFH and related risk factors after internal fixation of FNF from January 1th 2000 to July 1th 2020. Study extraction was performed according to inclusion and exclusion criteria. Endnote X9 and Excel 2019 were used for literatures extraction, management and data entry, and R Studio 3.6.5 software was used for Meta-analysis. Subgroup analysis, sensitivity analysis and publication bias detection were used to explore the sources of heterogeneity and the reliability of the evaluation results. RESULTS: A total of 16 studies with 5521 patients were included. Meta-analysis showed that the incidence of ONFH after internal fixation for adult FNF was 14.5% [95% CI(0.126-0.165)]. Fracture displacement[OR=0.27, 95%CI(0.21-0.35)] and reduction quality [OR=0.15, 95%CI(0.09-0.27)] were related risk factors for ONFH. The results of subgroup rate analysis showed that the non-displaced fracture necrosis rate was 6.2%[95%CI(0.051-0.077)] and the displaced fracture necrosis rate was 20.4% [95%CI(0.166-0.249)];the good reduction fracture necrosis rate was 8.3%[95%CI(0.072-0.095)] and the poor reduction fracture necrosis rate was 35.5%[95%CI(0.233-0.500)]. The included literatures have good consistency and no publication bias. CONCLUSION: After 2000, the total incidence of ONFH after internal fixation of adult FNF has decreased, while the necrosis rates of patients with displaced fracture and poor reduction are still at a high level. The interval between injury and surgery was not analyzed in this study because of the inconstant division in the original literature.

The Application of Machine Learning in Predicting Mortality Risk in Patients With Severe Femoral Neck Fractures: Prediction Model Development Study.

BACKGROUND: Femoral neck fracture (FNF) accounts for approximately 3.58% of all fractures in the entire body, exhibiting an increasing trend each year. According to a survey, in 1990, the total number of hip fractures in men and women worldwide was approximately 338,000 and 917,000, respectively. In China, FNFs account for 48.22% of hip fractures. Currently, many studies have been conducted on postdischarge mortality and mortality risk in patients with FNF. However, there have been no definitive studies on in-hospital mortality or its influencing factors in patients with severe FNF admitted to the intensive care unit. OBJECTIVE: In this paper, 3 machine learning methods were used to construct a nosocomial death prediction model for patients admitted to intensive care units to assist clinicians in early clinical decision-making. METHODS: A retrospective analysis was conducted using information of a patient with FNF from the Medical Information Mart for Intensive Care III. After balancing the data set using the Synthetic Minority Oversampling Technique algorithm, patients were randomly separated into a 70% training set and a 30% testing set for the development and validation, respectively, of the prediction model. Random forest, extreme gradient boosting, and backpropagation neural network prediction models were constructed with nosocomial death as the outcome. Model performance was assessed using the area under the receiver operating characteristic curve, accuracy, precision, sensitivity, and specificity. The predictive value of the models was verified in comparison to the traditional logistic model. RESULTS: A total of 366 patients with FNFs were selected, including 48 cases (13.1%) of in-hospital death. Data from 636 patients were obtained by balancing the data set with the in-hospital death group to survival group as 1:1. The 3 machine learning models exhibited high predictive accuracy, and the area under the receiver operating characteristic curve of the random forest, extreme gradient boosting, and backpropagation neural network were 0.98, 0.97, and 0.95, respectively, all with higher predictive performance than the traditional logistic regression model. Ranking the importance of the feature variables, the top 10 feature variables that were meaningful for predicting the risk of in-hospital death of patients were the Simplified Acute Physiology Score II, lactate, creatinine, gender, vitamin D, calcium, creatine kinase, creatine kinase isoenzyme, white blood cell, and age. CONCLUSIONS: Death risk assessment models constructed using machine learning have positive significance for predicting the in-hospital mortality of patients with severe disease and provide a valid basis for reducing in-hospital mortality and improving patient prognosis.

Prediction Model of Osteonecrosis of the Femoral Head After Femoral Neck Fracture: Machine Learning-Based Development and Validation Study.

BACKGROUND: The absolute number of femoral neck fractures (FNFs) is increasing; however, the prediction of traumatic femoral head necrosis remains difficult. Machine learning algorithms have the potential to be superior to traditional prediction methods for the prediction of traumatic femoral head necrosis. OBJECTIVE: The aim of this study is to use machine learning to construct a model for the analysis of risk factors and prediction of osteonecrosis of the femoral head (ONFH) in patients with FNF after internal fixation. METHODS: We retrospectively collected preoperative, intraoperative, and postoperative clinical data of patients with FNF in 4 hospitals in Shanghai and followed up the patients for more than 2.5 years. A total of 259 patients with 43 variables were included in the study. The data were randomly divided into a training set (181/259, 69.8%) and a validation set (78/259, 30.1%). External data (n=376) were obtained from a retrospective cohort study of patients with FNF in 3 other hospitals. Least absolute shrinkage and selection operator regression and the support vector machine algorithm were used for variable selection. Logistic regression, random forest, support vector machine, and eXtreme Gradient Boosting (XGBoost) were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model, and the external data were used to compare and evaluate the model performance. We compared the accuracy, discrimination, and calibration of the models to identify the best machine learning algorithm for predicting ONFH. Shapley additive explanations and local interpretable model-agnostic explanations were used to determine the interpretability of the black box model. RESULTS: A total of 11 variables were selected for the models. The XGBoost model performed best on the validation set and external data. The accuracy, sensitivity, and area under the receiver operating characteristic curve of the model on the validation set were 0.987, 0.929, and 0.992, respectively. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the model on the external data were 0.907, 0.807, 0.935, and 0.933, respectively, and the log-loss was 0.279. The calibration curve demonstrated good agreement between the predicted probability and actual risk. The interpretability of the features and individual predictions were realized using the Shapley additive explanations and local interpretable model-agnostic explanations algorithms. In addition, the XGBoost model was translated into a self-made web-based risk calculator to estimate an individual's probability of ONFH. CONCLUSIONS: Machine learning performs well in predicting ONFH after internal fixation of FNF. The 6-variable XGBoost model predicted the risk of ONFH well and had good generalization ability on the external data, which can be used for the clinical prediction of ONFH after internal fixation of FNF.

Prevalence of insomnia and anxiety among healthcare workers during the COVID-19 pandemic in Jilin Province.

The outbreak of the 2019 novel coronavirus disease (COVID-19) has impacted the mental health of healthcare providers at the frontline. Therefore, we conducted this study to estimate the prevalence rate of anxiety and insomnia and identify associated risk factors among healthcare workers in Jilin, China, during the period from January 25 to February 25, 2020. Zung's Self-Reported Anxiety Scale (SAS) and the Insomnia Severity Index (ISI) scale were used to diagnose anxiety and insomnia, respectively. Associated risk factors were identified through a multivariate logistic regression model. A total of 300 healthcare workers were invited and 236 completed the study. Of them, 234 (99.15%) were medical workers, 197 (83.47%) were working at frontline departments, and 159 (67.37%) were fighting against COVID-19. Fifty-seven respondents (24.15%) had anxiety (SAS index score ≥45) and 94 (39.83%) had insomnia (ISI score ≥8). Based on the multivariate analysis, contact with people from Hubei province during work (no vs not clear) [OR=0.25, 95%CI: 0.10-0.61] and personal protective equipment (PPE) (not in place vs in place) [OR=6.22, 95%CI: 2.23-17.40] were significantly correlated with anxiety. PPE (not in place vs in place) was the only significant risk factor of insomnia [OR=10.56, 95%CI: 4.00-27.87]. The prevalence of anxiety and insomnia was high in our study, reflecting the psychological impact of COVID-19 on healthcare workers. The unavailability of PPE in place was a significant risk factor of both anxiety and insomnia.

Prevalence of insomnia and anxiety among healthcare workers during the COVID-19 pandemic in Jilin Province

The outbreak of the 2019 novel coronavirus disease (COVID-19) has impacted the mental health of healthcare providers at the frontline. Therefore, we conducted this study to estimate the prevalence rate of anxiety and insomnia and identify associated risk factors among healthcare workers in Jilin, China, during the period from January 25 to February 25, 2020. Zung's Self-Reported Anxiety Scale (SAS) and the Insomnia Severity Index (ISI) scale were used to diagnose anxiety and insomnia, respectively. Associated risk factors were identified through a multivariate logistic regression model. A total of 300 healthcare workers were invited and 236 completed the study. Of them, 234 (99.15%) were medical workers, 197 (83.47%) were working at frontline departments, and 159 (67.37%) were fighting against COVID-19. Fifty-seven respondents (24.15%) had anxiety (SAS index score ≥45) and 94 (39.83%) had insomnia (ISI score ≥8). Based on the multivariate analysis, contact with people from Hubei province during work (no vs not clear) [OR=0.25, 95%CI: 0.10-0.61] and personal protective equipment (PPE) (not in place vs in place) [OR=6.22, 95%CI: 2.23-17.40] were significantly correlated with anxiety. PPE (not in place vs in place) was the only significant risk factor of insomnia [OR=10.56, 95%CI: 4.00-27.87]. The prevalence of anxiety and insomnia was high in our study, reflecting the psychological impact of COVID-19 on healthcare workers. The unavailability of PPE in place was a significant risk factor of both anxiety and insomnia.

Deficits in motor and cognitive functions in an adult mouse model of hypoxia-ischemia induced stroke.

Ischemic strokes cause devastating brain damage and functional deficits with few treatments available. Previous studies have shown that the ischemia-hypoxia rapidly induces clinically similar thrombosis and neuronal loss, but any resulting behavioral changes are largely unknown. The goal of this study was to evaluate motor and cognitive deficits in adult HI mice. Following a previously established procedure, HI mouse models were induced by first ligating the right common carotid artery and followed by hypoxia. Histological data showed significant long-term neuronal losses and reactive glial cells in the ipsilateral striatum and hippocampus of the HI mice. Whereas the open field test and the rotarod test could not reliably distinguish between the sham and HI mice, in the tapered beam and wire-hanging tests, the HI mice showed short-term and long-term deficits, as evidenced by the increased number of foot faults and decreased hanging time respectively. In cognitive tests, the HI mice swam longer distances and needed more time to find the platform in the Morris water maze test and showed shorter freezing time in fear contextual tests after fear training. In conclusion, this study demonstrates that adult HI mice have motor and cognitive deficits and could be useful models for preclinical stroke research.

SNP rs3202538 in 3'UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population.

BACKGROUND/AIMS: ErbB3 is an oncogene which has proliferation and metastasis promotion effects by several signaling pathways. However, the individual expression difference regulated by miRNA was almost still unknown. We focused on the miRNAs associated SNPs in the 3'-UTR of ErbB3 to investigate the further relationship of the SNPs with miRNAs among Chinese gastric cancer (GC) patients. METHODS: We performed case-control study including 851 GC patients and 799 cancer-free controls. Genotyping, real-time PCR assay, cell transfection, the dual luciferase reporter assay, western-blot, cell proliferation and trans-well based cell invasion assay were used to investigate the effects of the SNP on ErbB3 expression. Moreover, a 5-years-overall survival and relapse free survival were investigated between different genotypes. RESULTS: We found that patients suffering from Helicobacter pylori (Hp.) infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs3202538 (G/T) in ErbB3 3'-UTR was involved in the occurrence of GC by acting as tumor risk factors. SNP rs3202538 (G/T) could be regulated by both miR-204 and miR-211 which caused an upregulation of ErbB3 in patients. Furthermore, the carriers of T genotype was related to the significantly high expression of ErbB3, and to big tumor size, poor differentiation as well as the high probability of metastasis. Both miR-211 and miR-204 can significantly decrease cell proliferation, metastasis as well as downstream AKT activation through G but not T allele of ErbB3 3'UTR. Moreover, the SNP of G/T was associated with shorter survival of post-surgery GC patients with 5 years of follow up study. CONCLUSION: In conclusion, our findings have shown that the SNP rs3202538 (G/T) in ErbB3 3'-UTR acted as promotion factors in the GC development through disrupting the regulatory role of miR-204 and miR-211 in ErbB3 expression.

Structure characterization and immunocompetence of a glucan from the fruiting bodies of Cantharellus cibarius.

A protein-bound polysaccharide fraction (JBP-1) was obtained from the fruiting bodies of Cantharellus cibarius. Its chemical composition was studied by the cooperative usage of multiple chemical and spectral methods and characterized to be a fraction with a molecular weight of 4.8 × 10(5) Da and only composed of glucose. Methylation analysis revealed that the sugar residues in JBP-1 are existing as t-, 1,6-, and 1,3,6-linked Glcp sugar residues. The immunocompetence of the fraction was evaluated with the proliferation assay of mouse splenocytes, and the result revealed that JBP-1 could significantly stimulate the proliferation of mouse splenocytes in a dose-dependent manner, with p < 0.001 at the concentration of 100 µg/ml and 30 µg/ml, p < 0.05 at 10 µg/ml. These results give us a primary scientific evidence to further explore the pharmaceutical function of this mushroom.

Structure elucidation and immunological activity of a novel polysaccharide from the fruit bodies of an edible mushroom, Sarcodon aspratus (Berk.) S. Ito.

A water-soluble polysaccharide with a molar weight of 4.3x10(5)Da, termed as HBP was isolated from the fruit bodies of an edible mushroom, Sarcodon aspratus (Berk.) S. Ito. Composition, methylation analysis, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy experiments were conducted to elucidate its structure. The results indicated that HBP is a glucan featuring a backbone of (1-->6)-linked-beta-d-glucopyranosyl residues, which occasionally branched at O-3 position on along the backbone and substituted by the side chains that consisting of (1-->3)-linked-beta-d-glucopyranosyl, (1-->4)-linked-beta-d-glucopyranosyl and non-reducing end beta-d-glucopyranosyl residues. Immunological activity evaluation by H(3)-thymidine incorporation method revealed that HBP can significantly stimulate the proliferation of the cultured mice spleen lymphocyte in a dose-dependent manner, thus, HBP is a promising potential immunomodulator that can be used as healthcare food or medicine against pathogens and tumors.

[Multicenter controlled study on transient asthma-stopping action of acupuncture at "Qingchuan point"].

OBJECTIVE: To test and verify the transient therapeutic effect of acupuncture at point "Qingchuan" on bronchial asthma. METHODS: Two hundred cases of bronchial asthma at acute attack stage were divided into a trial group of 100 cases treated with acupuncture at point "Qingchuan" and a control group of 100 cases treated with acupuncture at Dingchuan (EX-B1). RESULTS: The total effective rate was 92.60% and the effect occurred within 42-860 seconds after acupuncture in the trial group, and 81.0% and within 114-126 seconds in the control group, respectively, with very significant differences between the two groups (P < 0.01, P < 0.001). CONCLUSION: Acupuncture at point "Qingchuan" can significantly improve asthmatic state in the patient of bronchial asthma with action of rapidly stopping asthma.