Objective To explore the relationship between the expression of Toll like receptor 4(TLR4)and Janus protein tyrosine kinase 3(JAK3)genes and the imbalance of helper T cell 17(Th17)/regulatory T cells(Treg)in peripheral blood mononuclear cells(PBMCs)of patients with ankylosing spondylitis(AS).Methods A total of 101 AS patients were selected as the AS group.According to the AS Disease Activity Index(BASDAI)score,patients were divided into the AS stable phase(ASS)group(＜4 points,42 cases)and the AS active phase(ASA)group(≥4 points,59 cases).Additionally,50 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group(health group).Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine the mRNA expression of TLR4 and JAK3 in PBMCs,and the proportion of serum Th17 and Treg was measured and Th17/Treg levels were calculated.Results The levels of TLR4 mRNA and JAK3 mRNA in PBMCs of peripheral blood were higher in the AS group than those in the health group(P＜0.05).The levels of Th17,proportion and Th17/Treg in peripheral blood were higher in the AS group than those of the health group(P＜0.05).Higher levels of TLR4 mRNA,JAK3 mRNA,Th17,and Th17/Treg were risk factors for AS,while higher level of Treg was protective factors for AS.TLR4 mRNA and JAK3 mRNA in AS patients were positively correlated with Th17 ratio and Th17/Treg ratio,and negatively correlated with Treg ratio(P＜0.05).Conclusion TLR4 and JAK3 genes are highly expressed and Th17/Treg is unbalanced in PBMC of AS patients.The high expression of TLR4 and JAK3 genes is closely related to Th17/Treg imbalance in AS patients.

Using high-energy proton to image the region of interest can directly obtain the accurate estimation of the proton stopping power of the lesions,which is of great significance to reduce the range uncertainty in proton therapy.As a fundamental function of proton computed tomography(CT),radiographic imaging plays a crucial role in assisting clinical positioning.The study develops a compact proton CT detector based on an active array pixel CMOS chip in Monte-Carlo simulation toolkit Geant4,and evaluates the radiographic imaging capability of the system using 180 MeV protons.The angles of tracks are successfully reconstructed.CTP404,CTP528,and the CTP515 of specific materials are used for simulation,obtaining the spatial and density resolutions,and measuring the proton relative stopping power(RSP).The image signal-to-noise ratio is improved when using 2° proton scattering angle cut-off value.The spatial resolution is 3-4 lp/cm measured using CTP528 module.The density resolution is better than 0.05 g/cm3,and the RSP resolution is within 5%when CTP404 module is used.Through the imaging of CTP515 phantom of specific material,it is demonstrated that the system has potential for imaging common human tissues.

Objective To investigate the effects of transcutaneous electrical acupoint stimulation(TEAS)combined with multimodal analgesia on short-term and long-term joint function after total knee arthroplasty(TKA).Methods Totally 110 patients with TKA were divided into the treatment group and the control group according to random number table method,with 55 cases in each group.The control group was treated with multimodal analgesia,and the treatment group was treated with TEAS on the basis of multimodal analgesia.The VAS score,pain threshold value,WOMAC score and SF-12 score of the two groups before and at different time points after operation were recorded and analyzed.Results The VAS score of the treatment group was lower than that of the control group on the 3rd and 7th day after operation(P<0.05).On the 7th day after operation,the knee pain threshold in the treatment group was higher than that in the control group(P<0.05).The WOMAC score of the treatment group was lower than that of the control group at the 1st,2nd,4th and 12th week after operation(P<0.05).At the 4th and 12th week after operation,the SF-12 score of the treatment group was higher than that of the control group(P<0.05).Conclusion TEAS combined with multimodal analgesia can relieve the pain after TKA,and promote the recovery of joint function in the short term and long term,and the improvement effect in the short term is more obvious than that in the long term.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

Objective To provide a scientific benchmark for the era of population aging and improve the medical care environment for the elderly in terms of hospital facility accessibility.Methods A random sampling method was used to select 375 individuals from 10 healthcare institutions in a specified city as survey participants from December 2022 to February 2023.A total of 375 questionnaires titled"Comprehensive Rating Scale for Patient Experience in Medical Facilities(Accessibility Category)"were distributed among the participants,with 356 valid responses received and subjected to reliability and validity assessments.The questionnaire included 6 accessibility indicators,each rated from 1 to 10,to evaluate the accessibility level of healthcare fa-cilities.The acquired data was analyzed using the Rank Sum Ratio method and the Four Quadrants model.Results The average score for building accessibility in the city's medical institutions was 35.86,with several indicators at a moderate level,indicating a need for an improvement of the facility accessibility.Meanwhile,the economic operational status of various medical institutions appeared to influence the implementation of accessibility features,which also correlated with local government construction plan-ning,staff awareness of accessible infrastructure,and other factors.Conclusion Medical facilities in cities could implement bar-rier-free modifications in parking,toilets,and other areas,improve the use of accessible AI technology,and develop intelligent medical scenarios in order to meet the challenges of an aging society,improve the medical care quality for the elderly,and reduce social security cost.The governments should accelerate the improvement of supportive policies and regulations and bolster support for the accessibility enhancements.Higher education and research institutions can collaborate with healthcare providers for innova-tive integration of industry academia,research,and application,fostering the conversion of research into practical solutions.

Objective The contents of 11 nucleosides and base components in 10 batches of samples from 5 provinces(cities)including Chongqing,Yunnan and Shaanxi were determined,and the differences in nucleosides and base components in Fritillaria taipaiensis were compared by chemometric analysis,and the quality was comprehensively evaluated,so as to provide a reference for the cultivation of excellent varieties and the selection of medicinal materials.Methods Nucleoside and base components were extracted from Fritillaria taipaiensis by ultrasonication in aqueous solutions,and the content of each component was determined by HPLC-DAD method.The origin was classified by principal component analysis(PCA)and hierarchical cluster analysis(HCA).Partial least squares discriminant analysis(PLS-DA)was used to determine the differentiated index components in Fritillaria taipaiensis.Then the differences in the contents of the index components among samples from different origins were compared.Results It was found that 11 nucleoside and base components differed significantly among different origins of Fritillaria taipaiensis.Principal component analysis and hierarchical cluster analysis indicated that all samples could be clustered into 4 categories.Five characteristic components,including uracil,cytosine,uridine,inosine,and adenosine,were identified by PLS-DA.The nucleosides and bases in samples from Chongqing and Hubei were relatively high,and the quality of the samples was comparatively superior.Conclusion This method is simple,reproducible,accurate and reliable.It has screened out the index nucleoside and base components in the identification of Fritillaria taipaiensis of different origins,which can be used to initially elucidate the differences of samples between different origins.Additionally,it can better reflect the quality of Fritillaria taipaiensis,and can provide reference for the selection of procurement origin and the quality control for Fritillaria taipaiensis.

Objective To investigate the value of T2 mapping sequence combined with apparent diffusion coefficient(ADC)values in identifying benign and malignant breast lesions.Methods Ninety-two patients with breast mass were retrospectively selected,all patients received MRI examination,T2 mapping sequence and ADC values were selected for image analysis,and all patients underwent surgical biopsy and pathological diagnosis,the clinical value of T2 mapping sequence combined with ADC values in differential diagnosis of benign and malignant breast lesions was observed.Results After pathological examination,52 patients were diagnosed as malignant breast lesions and the remaining 40 were diagnosed as benign breast lesions.Among 52 patients with malignant lesions,51 were diag-nosed as malignant and 1 was diagnosed as benign by ADC values.Among the 40 cases of benign lesions,16 were diagnosed as malig-nant and 24 were diagnosed as benign by ADC values.The difference between the mean T2 values of benign breast lesions and malig-nant breast lesions was not significant(P＞0.05);but the coefficient of variation(CV)of T2 values of malignant breast lesions was significantly higher than that of benign breast lesions,and the difference was significant(P＜0.05),and the diagnostic efficacy of T2 mapping and ADC value single examination was lower than that of the combined examination(P＜0.05).Conclusion T2 mapping sequence and ADC value in MRI have the ability to diagnose and distinguish benign and malignant breast,especially the value of the joint application of the two is more prominent,improve the diagnostic accuracy,sensitivity and specificity,and can provide more accurate reference information for clinical practice,which is worth popularizing.

Objective:To investigate the effect and molecular mechanism of high concentration of IL-17A on osteoclast differentiation by inhibiting autophagy of osteoclast precursor cells through PI3K/Akt pathway.Methods:With RANKL (50 ng/ml) inducing osteoclast precursor cells (osteoclast we cells, OCPs), osteoclast differentiation model is set up. In osteoclast differentiation model of high levels of IL-17A (100 ng/ml), RAW264.7 cells were divided into negative control CTR-N group, CTR-R group with RANKL, IL-17A group, IL-17A+LY294002 group. BMMs were divided into negative control CTR-N group with M-CSF, CTR-R group, IL-17A group and IL-17A+LY294002 group with M-CSF and RANKL. IL-17A was applied to OCPs, and tartrate-resistant acid phosphatase (TRAP) staining was used to observe the number of osteoclast differentiation. The number of autolysosomes was observed under transmission electron microscope. RAW264.7 was treated with IL-17A. Western blot was used to detect the relative expression levels of p-Akt/Akt, p-mtor/mTOR, p-PI3K/PI3K, p-ULK1/ULK1, Cleaved-caspase3/caspase3, Beclin1/β-actin. The apoptosis rate of RAW264.7 cells treated with IL-17A was detected by flow cytometry. OCPs were treated with IL-17A and PI3K inhibitor LY294002, and TRAP staining was used to observe the number of osteoclast differentiation.Results:The TRAP staining showed that the positive ratio for RAW264.7 cells CTR-N group, CTR-R group, IL-17A group was 1.33%±0.58%, 100%±3.01%, 51.11%±4.02% with that of IL-17A significantly lower than CTR-R group ( t=16.970, P<0.05). The positive rates of BMMs in the CTR-N group, CTR-R group and IL-17A group were 1.67%±0.58%, 100%±1.01% and 50.33%±2.52%, respectively, with that of IL-17A group significantly lower than CTR-R group ( t=31.770, P<0.05). Transmission electron microscopy showed that the number of autophagosomes in RAW264.7 cells in CTR-R group and IL-17A group were 3.67±1.53 and 0.67±0.58, respectively, with significant difference between the groups ( t=3.182, P<0.05). While in BMMs cells CTR-R group and IL-17 the numbers of autophagosome were 3.00±1.00 and 0.33±0.58 with significant difference ( t=4.000, P<0.05); Western blot results showed 0.69±0.03、0.69±0.13、1.47±0.13、0.78±0.04、0.66±0.10、0.82±0.03 for RAW264.7 cells CTR-R group Akt/Akt, p-mTOR/mTOR, p-PI3K/PI3K, p-ULK1/ULK1, Cleaved caspase3/caspase3, Beclin1/β-Actin and 0.89±0.04、1.14±0.18、1.87±0.04、0.53±0.09、0.93±0.02、0.54±0.03 for RAW264.7 cells IL-17A group p-Akt/Akt, p-mTOR/mTOR, p-PI3K/PI3K, p-ULK1/ULK1, Cleaved caspase3/caspase3, Beclin1/β-Actin with significant difference ( t=6.708; t= 3.497; t=5.424; t=4.542; t=4.638; t=11.220, all P<0.05); Flow cytometry detection showed that in CTR-R group, IL-17A RAW264.7 cells apoptosis rates of group A were 6.92%±0.62%, 12.12%±0.69%, with significant difference between the two groups ( t=9.747, P<0.05); After using LY294002 TRAP staining, it showed a positive result of 9.00%±2.00%, 158.33%±3.51%, 100%±2.65% and 128.99%±4.01% for CTR-N, CTR-R, IL-17A and IL-17A+LY294002 in RAW264.7 cells respectively with significant difference between IL-17A+LY294002 group and the IL-17A in group A ( t=10.470, P<0.05). For BMMs cells CTR-N, CTR-R group, IL-17A in group, IL-17A+LY294002 group, the positive rate was 8.01%±0.99%, 151.67%±4.51%, 100%±3.61%, with significant difference between IL-17A+LY294002 group and IL-17A group ( t=6.535, P<0.05). Conclusion:High concentration of IL-17A inhibits osteoclast differentiation by inhibiting autophagy of osteoclast precursor cells through PI3K/Akt pathway.

Hepatocellular carcinoma (HCC) is the most common liver malignancy, where HCC segmentation and prediction of the degree of pathological differentiation are two important tasks in surgical treatment and prognosis evaluation. Existing methods usually solve these two problems independently without considering the correlation of the two tasks. In this paper, we propose a multi-task learning model that aims to accomplish the segmentation task and classification task simultaneously. The model consists of a segmentation subnet and a classification subnet. A multi-scale feature fusion method is proposed in the classification subnet to improve the classification accuracy, and a boundary-aware attention is designed in the segmentation subnet to solve the problem of tumor over-segmentation. A dynamic weighted average multi-task loss is used to make the model achieve optimal performance in both tasks simultaneously. The experimental results of this method on 295 HCC patients are superior to other multi-task learning methods, with a Dice similarity coefficient (Dice) of (83.9 ± 0.88)% on the segmentation task, while the average recall is (86.08 ± 0.83)% and an F1 score is (80.05 ± 1.7)% on the classification task. The results show that the multi-task learning method proposed in this paper can perform the classification task and segmentation task well at the same time, which can provide theoretical reference for clinical diagnosis and treatment of HCC patients.
Humans ; Carcinoma, Hepatocellular ; Liver Neoplasms ; Learning

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.