ObjectiveTo investigate whether the CD151 YXXφ motif point mutant affects vascular permeability by regulating vesicle internalization and recycling. MethodsCD151 knockout （KO） and wild-type （WT） mice were used. A modified Miles assay was performed to compare vascular permeability in the dorsal and postauricular skin of the two groups of mice under vascular endothelial growth factor A （VEGF-A） stimulation. The CD151 YXXφ motif point mutant YALA was constructed and transfected into human endothelial cells （EA.hy926） using an adenoviral vector. Multiple experimental groups were set up to detect the permeability of endothelial cell monolayers to FITC-dextran under baseline conditions and after VEGF-A stimulation. Western blot （WB）， RT-qPCR， and immunofluorescence were used to examine the expression and distribution of VE-cadherin. The internalization rate of VE-cadherin was quantitatively compared using a cell surface biotinylation assay. Phalloidin was used to label F-actin to observe changes in cytoskeletal tension. ResultsThe Miles assay showed that under VEGF-A stimulation， dye extravasation in the dorsal and postauricular skin of KO mice was significantly higher than that in WT mice （all P<0.05）. At 60 min and 120 min after VEGF-A stimulation， the permeability of endothelial cell monolayers overexpressing the YALA mutant to FITC-dextran significantly increased （P<0.05）. WB and RT-qPCR results indicated that the YALA mutant did not affect the total protein or mRNA expression levels of VE-cadherin. Immunofluorescence revealed that the YALA mutant disrupted the continuous distribution of VE-cadherin on the cell membrane and its perinuclear co-localization with CD151 under VEGF-A stimulation. The cell surface biotinylation assay confirmed that the YALA mutant significantly reduced the internalization rate of VE-cadherin （P<0.05）. Cytoskeletal staining showed that the YALA mutant caused the formation of thick tension fibers in the actin cytoskeleton of endothelial cells， indicating cell contraction. ConclusionThe CD151 YXXφ motif point mutation affects vesicle internalization and recycling in endothelial cells， influences the expression and internalization of VE-cadherin， and consequently affects vascular permeability.

OBJECTIVE To analyze the diagnosis of latent tuberculosis infection(LTBI)in hospitalized patients of a tertiary general hospital and investigate the current status of related comorbidities.METHODS The clinical data were collected from the 14 448 hospitalized patients who received tuberculin skin test(TST)or interferon-gamma release assay(IGRA)in China-Japan Friendship Hospital from Jan.1,2022 to Dec.31,2023,and the results were assessed.RESULTS The detection rate of LTBI was 23.62％(3413/14448)among the hospitalized patients who received the tests,and the rate of definite diagnosis was only 4.22％(144/3413).88.40％(3017/3413)of the hospitalized patients with LTBI had at least one type of comorbidity,and the top 5 comorbidities were in turn as follows:high blood pressure,hyperlipidemia,diabetes mellitus,malignant tumors and rheumatic immune disea-ses;the number of comorbidities was increased with the age(x2=291.199,P＜0.001).The rheumatic immune disease(73/144,50.69％)was the most common type of comorbidity among the hospitalized patients with definite diagnosis of LTBI,and less than half of the patients(66/144,45.83％)were treated in rheumatology and immu-nology department.CONCLUSION The two-way screening of LTBI and comorbidities is the core premise for the standardized management of LTBI.

OBJECTIVE To analyze the diagnosis of latent tuberculosis infection(LTBI)in hospitalized patients of a tertiary general hospital and investigate the current status of related comorbidities.METHODS The clinical data were collected from the 14 448 hospitalized patients who received tuberculin skin test(TST)or interferon-gamma release assay(IGRA)in China-Japan Friendship Hospital from Jan.1,2022 to Dec.31,2023,and the results were assessed.RESULTS The detection rate of LTBI was 23.62％(3413/14448)among the hospitalized patients who received the tests,and the rate of definite diagnosis was only 4.22％(144/3413).88.40％(3017/3413)of the hospitalized patients with LTBI had at least one type of comorbidity,and the top 5 comorbidities were in turn as follows:high blood pressure,hyperlipidemia,diabetes mellitus,malignant tumors and rheumatic immune disea-ses;the number of comorbidities was increased with the age(x2=291.199,P＜0.001).The rheumatic immune disease(73/144,50.69％)was the most common type of comorbidity among the hospitalized patients with definite diagnosis of LTBI,and less than half of the patients(66/144,45.83％)were treated in rheumatology and immu-nology department.CONCLUSION The two-way screening of LTBI and comorbidities is the core premise for the standardized management of LTBI.

Bispecific antibodies(BsAbs),as an important recent innovation in the field of tumor immunotherapy in recent years,can simultaneously or sequentially target different antigens or two different epitopes of the same antigen.Compared with traditional monoclonal antibodies,they can produce superior therapeutic effects.This article reviews the progress in clinical applications and safety research of BsAbs in cancer therapy,revealing that they(such as blinatumomab,glofitamab,teclistamab,amivantamab,etc.)exhibit significant therapeutic efficacy against hematological malignancies,lung cancer,cervical cancer,melanoma,and other cancers.For cytokine release syndrome(CRS)induced by BsAbs,prophylactic or pre-emptive medication is commonly administered in clinical practice;for neurotoxicity and infections triggered by BsAbs,clinical practice necessitates rigorous monitoring of patients'vital signs and the provision of essential treatments.In addition,different BsAbs exhibit variations in escalation dose,infusion rate,storage duration,and equipment requirements.Therefore,strict adherence to the instructions in the drug package inserts is essential during clinical operations to ensure safety and therapeutic efficacy.In the future,more multicenter trials need to be conducted to validate the efficacy and safety of BsAbs across different tumor types and patient populations,and long-term follow-up data should be accumulated to optimize treatment cycles and dosage regimens.

Objective To investigate the relationship between left ventricular myocardial fibrosis and right ventricular function injury in coronary heart disease(CHD)using cardiac magnetic resonance(CMR).Methods A total of 40 CHD patients and 32 healthy volunteers were selected.Based on the late gadolinium enhancement(LGE)images,CHD patients were divided into LGE(+)and LGE(-)groups.Biventricular function parameters,T1 value of the left ventricular myocardium and left ventricular LGE extent(％LGE)were measured and compared between the two groups.Pearson or Spearman correlation analysis was used to analyze the relationship among CMR parameters.Multivariate logistic regression was used to analyze the related factors of right ventricular dysfunction.Results Compared with the LGE(-)group,the right ventricular ejection fraction(RVEF),right ventricular stroke volume index(RVSVI)and right ventricular fractional area change(RVFAC)were decreased in the LGE(+)group(P<0.05).RVEF,RVSVI and RVFAC were negatively correlated with％LGE and native T1 value of the left ventricular myocardium,and native T1 value of the left ventricular myocardium was independently correlated with right ventricular dysfunction(P<0.05).Conclusion CMR reveals the relationship between left ventricular myocardial fibrosis and right ventricular function injury in CHD patients,which is helpful for the early clinical detection and treatment of right ventricular injury.

Objective To evaluate the clinical efficacy of selective expansive open-door laminoplasty(SEOLP)with preservation of C7 spinous process in the treatment of multisegmental cervical spondylotic myelopathy and its impact on changes in sagittal parameters of cervical spine.Methods A retrospective analysis was conducted on the clinical data and radiological information of 73 patients who underwent expansive open-door laminoplasty(EOLP)for cervical spondylotic myelopathy in our department between March 2018 and June 2022.Patients were divided into the SEOLP group(n=35)and the EOLP group(n=38)based on the surgical method.Follow-up was conducted for one year.The operation time,blood loss,axial symptom scores,JOA scores,VAS scores and neck disability index(NDI)were recorded in two groups of patients.Radiological data were also recorded for both groups during the perioperative period,and the C2-7 Cobb angle,C2-7 SVA and T1 slope were measured.The cervical curvature index(CCI)and cervical range of motion(ROM)were calculated.The perioperative clinical outcomes and changes in cervical sagittal parameters were observed,and their correlations were analyzed.Results There were no significant differences in blood loss,operation time,JOA scores at various follow-up time points between the two groups(P＞0.05).During postoperative follow-up,axial symptoms were observed in 5 patients in SEOLP group and 14 patients in EOLP group.There were statistically significant differences in axial symptom scores,incidence and severity of axial symptoms between the two groups(P＜0.05).The NDI indices at one year after operation were 21.1±2.3 for SEOLP group and 24.8±3.5 for EOLP group respectively(P＜0.01).There were no statistically significant differences in T1 slope and C2-7 Cobb angle at various follow-up time points after surgery between the two groups(P＞0.05).One year after operation,CCI indices for two groups were(13.4±2.7)and(12.1±2.4),respectively,with a statistically significant difference(t=2.178,P＜0.05).The C2-C7 SVA values for two groups at one year after operation were(22.4+3.8)mm and(26.7±5.9)mm,respectively(t=3.667,P＜0.01).The results of the correlation analysis showed that there was a significant negative correlation between clinical functional improvement(NDI)and changes of the radiological parameter C2-C7 SVA in both groups of patients.Conclusion After SEOLP,the recovery of C2-C7 SVA is faster and has less impact on cervical spine function,and the occurrence degree and incidence of axial symptoms are lower.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

Objective To investigate the relationship between left ventricular myocardial fibrosis and right ventricular function injury in coronary heart disease(CHD)using cardiac magnetic resonance(CMR).Methods A total of 40 CHD patients and 32 healthy volunteers were selected.Based on the late gadolinium enhancement(LGE)images,CHD patients were divided into LGE(+)and LGE(-)groups.Biventricular function parameters,T1 value of the left ventricular myocardium and left ventricular LGE extent(％LGE)were measured and compared between the two groups.Pearson or Spearman correlation analysis was used to analyze the relationship among CMR parameters.Multivariate logistic regression was used to analyze the related factors of right ventricular dysfunction.Results Compared with the LGE(-)group,the right ventricular ejection fraction(RVEF),right ventricular stroke volume index(RVSVI)and right ventricular fractional area change(RVFAC)were decreased in the LGE(+)group(P<0.05).RVEF,RVSVI and RVFAC were negatively correlated with％LGE and native T1 value of the left ventricular myocardium,and native T1 value of the left ventricular myocardium was independently correlated with right ventricular dysfunction(P<0.05).Conclusion CMR reveals the relationship between left ventricular myocardial fibrosis and right ventricular function injury in CHD patients,which is helpful for the early clinical detection and treatment of right ventricular injury.

Deep learning method can be used to automatically analyze electrocardiogram (ECG) data and rapidly implement arrhythmia classification, which provides significant clinical value for the early screening of arrhythmias. How to select arrhythmia features effectively under limited abnormal sample supervision is an urgent issue to address. This paper proposed an arrhythmia classification algorithm based on an adaptive multi-feature fusion network. The algorithm extracted RR interval features from ECG signals, employed one-dimensional convolutional neural network (1D-CNN) to extract time-domain deep features, employed Mel frequency cepstral coefficients (MFCC) and two-dimensional convolutional neural network (2D-CNN) to extract frequency-domain deep features. The features were fused using adaptive weighting strategy for arrhythmia classification. The paper used the arrhythmia database jointly developed by the Massachusetts Institute of Technology and Beth Israel Hospital (MIT-BIH) and evaluated the algorithm under the inter-patient paradigm. Experimental results demonstrated that the proposed algorithm achieved an average precision of 75.2%, an average recall of 70.1% and an average F ₁-score of 71.3%, demonstrating high classification accuracy and being able to provide algorithmic support for arrhythmia classification in wearable devices.
Humans ; Arrhythmias, Cardiac/diagnosis* ; Algorithms ; Electrocardiography/methods* ; Neural Networks, Computer ; Signal Processing, Computer-Assisted ; Deep Learning ; Classification Algorithms