Objective:Inflammation has been confirmed to play an important role in the occurrence and development of sudden sensorineural hearing loss（SSNHL）, and the neutrophil-to-lymphocyte ratio（NLR） is a biomarker positively correlated with the degree of inflammation. This study aims to identify the difference in serum NLR between patients with SSNHL and normal population, and to evaluate the predictive efficacy of NLR for the occurrence and prognosis of SSNHL, thereby guiding the clinical diagnosis and treatment of SSNHL. Methods:In this study, 96 patients diagnosed with SSNHL admitted to our department from January 2023 to March 2024 and 96 patients diagnosed with vocal cord polyps admitted to our department during the same period were recruited as a control group. Multivariate Logistic regression was used to evaluate independent related factors, and a nomogram was constructed to predict the probability of SSNHL. The receiver operating characteristic（ROC） curve and calibration curve were used to evaluate the accuracy of prediction. Results:Multivariate logistic regression analysis showed that a high level NLR（OR2.215; 95%CI1.597-3.073; P<0.001） were independently associated with the presence of SSNHL. High age（OR1.036; 95%CI1.009-1.067; P=0.012）, high FIB（OR2.35; 95%CI1.176-4.960; P=0.019） were the risk factor for SSNHL. Incorporating these 3 factors, a forest plot and a nomogram were generated. The ROC curve, nomogram and calibration curve showed that the model had good clinical practicability. A low NLR（OR0.598; 95%CI0.439-0.816; P<0.001） was significantly associated with a favorable prognosis of SSNHL. Conclusion:Elevated NLR can serve as an promising biomarker for assessing the risk of SSNHL. The nomograms calculation model may be utilized as a tool to estimate the probability of SSNHL. Low level NLR is significantly associated with a good prognosis of SSNHL.
Humans ; Neutrophils ; Female ; Male ; Lymphocytes ; Hearing Loss, Sensorineural/blood* ; Hearing Loss, Sudden/diagnosis* ; Middle Aged ; Prognosis ; Nomograms ; ROC Curve ; Adult ; Logistic Models ; Biomarkers/blood* ; Lymphocyte Count ; Inflammation/blood* ; Clinical Relevance

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.

BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.

Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Objective:To analyze brain topological property data through machine learning methods and explore changes in brain network topological properties in patients with schizophrenia.Methods:From January 2022 to August 2023, functional magnetic resonance imaging data of 60 patients with schizophrenia and 56 healthy controls were collected , and the data were preprocessed to construct brain functional networks and extract global and nodal topological properties. All subjects were divided into a training group and a testing group.The data of training group were fitted based on support vector machine, and the predictive performance was evaluated through cross-validation.The model was optimized by recursive feature elimination algorithm, then the indicators that contributed the most to predictive performance were extrated.The classification performance of the testing group was calculated based on the trained model with optimal predictive performance.SPSS 20.0 software was used for data analysis, the independent t-test and χ2 test were used for comparing the differences between the two groups. Results:The support vector machine achieved an accuracy of 75.00% in predicting the test group of schizophrenia patients based on all indicators. After removing redundant features and combining with the recursive feature elimination algorithm, the accuracy of the SVM model in predicting the test group increased to 90.00%. The nodal global efficiency(Ne)of the left superior temporal gyrus, right dorsal agranular insula, bilateral dorsal granular insula, bilateral caudal cingulate gyrus, and left lateral orbitofrontal cortex in the model contributed the most to classification.Compared to the control group, patients with schizophrenia had abnormal Ne values in these brain regions.Conclusion:There are multiple brain regions with abnormal Ne values in patients with schizophrenia, indicating that the abnormalities in information integration and transmission functions may be related to the imbalance in the dynamic equilibrium of the patients' brain networks.

Objective:To investigate the current status of scientific fitness literacy (SFL) and its influencing factors among Chinese adults aged 20-59 years.Methods:Totally 63 338 adults aged 20-59 years in the status of national fitness activities in 2020 from 1 January to 31 March 2020 were selected as the subjects, and they were divided into four age groups, namely, the 20-29 age group, the 30-39 age group, the 40-49 age group and the 50-59 age group. Data were analyzed by SPSS 29.0.Comparative analyses for age, gender, urban-rural difference were carried out by applying non-parametric tests, and multiple regression models were applied to find the influencing factors of SFL.Results:The SFL score of Chinese adults aged 20-59 years was 53.40 (41.67, 63.73), and the scores of cognition, attitude, ability and skills, behavior and habits sub-dimensions were 86.11 (72.22, 100.00), 62.96 (50.62, 75.31), 27.78 (11.11, 44.44) and 33.33 (11.11, 55.56), respectively. The SFL and the four sub-dimensions were demonstrated to have higher scores for males than females, and higher scores for adults in urban area than those in rural area(all P<0.01). The multiple regression results showed that regular exercise at a fitness facility (20-29 age group: β=0.321, t=5.940, P<0.01; 30-39 age group: β=0.187, t=2.937, P<0.01; 40-49 age group: β=0.230, t=3.988, P<0.01; 50-59 age group: β=0.415, t=5.671, P<0.01) was the Chinese adults' common influence factor on SFL.Motivation, evaluation by those around them, experience from exercising, and convenience and atmosphere of exercising were the main influence factors in the 20-29 and 30-39 age groups(all P<0.05).Comfort level of fitness venue, convenience, safety, and support of fitness place were the main influence factors in adults aged 40-59 years(all P<0.05). Conclusions:Chinese adults aged 20-59 years old have high SFL awareness scores, but low overall SFL scores. Surrounding people's evaluation, experience in exercise, comfort level of fitness place, convenience, safety and fitness policy support are the influential factors of scientific fitness literacy.

Objective:To explore the characteristic of dynamic function network connectivity (dFNC) of resting brain networks in internet gaming disorder (IGD) adolescents.Methods:Forty-four adolescent IGD subjects (IGD group, male/female: 38/6) and fifty healthy controls (HC group, male/female: 40/10) were collected, and the subjects completed demographic questionnaires, Young internet addiction scale(YIAS), Chinese adolescents' maladaptive cognitions scale(CAMAS), and functional magnetic resonance imaging (fMRI) tests. The fMRI data were preprocessed on the Matlab platform, and the preprocessed data was divided into 64 components for group level independent component analysis.The dynamic functional connectivity of obtained 18 effective independent components was analyzed by sliding time window technique, and the difference of dynamic functional connectivity of brain triple network between the IGD group and HC group was compared using SPSS 22.0 software.Results:Four repeated dFNC states were identified through cluster analysis.Each state indicated that different functional networks had different connection strengths.State 3, the most frequent state, had been indicated that the whole brain network of the subject was in a state of weak functional connectivity.The second frequent state was state 1, which indicated enhanced functional connectivity within the subject's central executive network (CEN).State 2 had been indicated enhanced functional connectivity within the subject's salience network (SN).State 4 had been indicated generally enhanced functional connectivity in the subjects' brain networks, and this state was the least frequent.The results of non-parametric permutation test on the time attribute showed that compared with the HC group, the IGD group had a longer time score (IGD group: 0.24±0.19, HC group: 0.13±0.15, t=1.19, P<0.05, non-parametric substitution test) for state 1 with strong connectivity within the CEN, which was positively correlated with the YIAS score and game time ( r=0.418, P=0.003; r=0.515, P=0.004).Compared with HC group, the functional connectivity of ICD group between the internal insula of the SN and the dorsal anterior cingulate cortex was enhanced ( P<0.05, FDR corrected), while the average residence time in weakly connected state 3 was longer ( Z=2.09, P<0.05, nonparametric substitution test). Conclusions:The difference in dynamic functional connectivity of the triple network in the brain of IGD adolescents under resting state is mainly manifested by strong connections in CEN, functional connections between insula and dorsal anterior cingulate cortex in SN is enhanced, and weakening of overall functional connections, which may play an important role in the pathological mechanism of IGD.

Objective:To investigate the effect of the ratio of the maximum diameter of aneurysm sac to age (R) on the long-term efficacy of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in patients with infrarenal abdominal aortic aneurysm (IAAA).Methods:This is a retrospective cohort study.The clinical data of 317 patients with IAAA who underwent surgical repair in the Department of Vascular Surgery,the Third Affiliated Hospital of Sun Yat-Sen University from January 2016 to October 2022 were retrospectively collected.There were 266 males and 51 females,aged (69.7±8.3) years (range:37 to 87 years).The R value of the patient was calculated and the receiver operating characteristic(ROC) curve was used to establish a model to calculate the optimal cut-off value.The propensity score matching method was used to match the baseline data of patients in the EVAR and OSR group by 3∶1 (the caliper value was 0.05),and the patients were stratified according to the cutoff value of R, and the postoperative efficacy and survival of the patients were analyzed.The primary endpoint was the total mortality rate,and the secondary endpoints included the occurrence of postoperative complications and reintervention.Pearson χ2 or Fisher ′s exact test was used for categorical variables, and independent sample t test or Wilcoxon rank sum test was used for continuous variables to compare differences between groups.The survival curves of the two groups were described by Kaplan-Meier method. Results:After propensity score matching,198 cases were in the EVAR group and 66 cases were in the OSR group.The ROC model showed that the best cut-off value of R value was 0.90,and the two groups were divided into two layers:R<0.90 and R≥0.90.Among them,112 patients with R<0.90 (84 cases of EVAR,28 cases of OSR);there were 152 patients with R≥0.90 (114 cases of EVAR and 38 cases of OSR).The follow-up time was (23.6±1.6) months (range:1 to 70 months).In the R≥0.90 stratification,the total mortality (26.3% vs.5.3%, χ2=7.600， P=0.006),complication rate (44.7% vs.26.3%, χ2=4.025， P=0.045), and secondary intervention rate (31.6% vs.13.2%, χ2=4.910， P=0.027) in the EVAR group were higher than those in the OSR group.In the R<0.90 stratification,there was no significant difference in the total mortality rate (13.1% vs.10.7%, χ2=0.109， P=0.741), complication rate (28.6% vs.35.7%, χ2=0.507， P=0.477) and secondary intervention rate (14.3% vs.21.4%, χ2=0.353， P=0.552) between the two groups. Conclusions:When R≥0.90 in IAAA patients,OSR maybe more beneficial to patients in terms of survival rate,postoperative complication rate and secondary intervention rate than EVAR.When R<0.90,there are no significant differences in survival rate,complication rate and secondary intervention rate between the two surgical methods.

Objective:To establish a set of artificial intelligence (AI) verification rules for blood routine analysis.Methods:Blood routine analysis data of 18 474 hospitalized patients from the First Hospital of Jilin University during August 1st to 31st, 2019, were collected as training group for establishment of the AI verification rules,and the corresponding patient age, microscopic examination results, and clinical diagnosis information were collected. 92 laboratory parameters, including blood analysis report parameters, research parameters and alarm information, were used as candidate conditions for AI audit rules; manual verification combining microscopy was considered as standard, marked whether it was passed or blocked. Using decision tree algorithm, AI audit rules are initially established through high-intensity, multi-round and five-fold cross-validation and AI verification rules were optimized by setting important mandatory cases. The performance of AI verification rules was evaluated by comparing the false negative rate, precision rate, recall rate, F1 score, and pass rate with that of the current autoverification rules using Chi-square test. Another cohort of blood routine analysis data of 12 475 hospitalized patients in the First Hospital of Jilin University during November 1sr to 31st, 2023, were collected as validation group for validation of AI verification rules, which underwent simulated verification via the preliminary AI rules, thus performance of AI rules were analyzed by the above indicators. Results:AI verification rules consist of 15 rules and 17 parameters and do distinguish numeric and morphological abnormalities. Compared with auto-verification rules, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score of AI rules in training group were 22.7%, 1.6%, 74.5%, 1.3%, 75.7%, 97.2%, 93.5%, 94.7%, 94.1, respectively.All of them were better than auto-verification rules, and the difference was statistically significant ( P<0.001), and with no important case missed. In validation group, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score were 19.2%, 8.2%, 70.1%, 2.5%, 72.6%, 89.2%, 70.0%, 88.3%, 78.1, respectively, Compared with the auto-verification rules, The false negative rate was lower, the false positive rate and the recall rate were slightly higher, and the difference was statistically significant ( P<0.001). Conclusion:A set of the AI verification rules are established and verified by using decision tree algorithm of machine learning, which can identify, intercept and prompt abnormal results stably, and is moresimple, highly efficient and more accurate in the report of blood analysis test results compared with auto-vefication.