This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective:To explore the correlations of brain network functional connectivity (FC) alterations with cerebrospinal fluid (CSF) pathological biomarkers in patients with Alzheimer's disease (AD).Methods:A total of 39 patients with cognitive impairment, admitted to Department of Neurology, Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2020 to December 2022 were recruited; 23 patients were with AD and 16 with non-AD. Clinical data were compared between the 2 groups. Resting-state functional MRI (rs-fMRI) data were collected, and FC differences between brain networks and FC differences within brain networks were compared by independent component analysis. Correlations of FC differences between brain networks and FC differences within brain networks with concentrations of β-amyloid protein 1-42 (Aβ 1-42) and Tau protein in CSF were analyzed. Results:Compared with the non-AD group, AD group had significantly lower Aβ 1-42 in CSF ( P<0.05). Compared with those in the non-AD group, FC alterations between the left frontoparietal network (lFPN) and anterior default mode network (aDMN) and between the visual network (VN) and posterior cingulate cortex (PCC), as well as FC alterations in lFPN, were significantly increased in AD group ( P<0.05). Compared with those in the non-AD group, FC alterations between lFPN and cerebellar network (CEN), and FC alterations in aDMN, sensorimotor network (SMN) and VN were significantly decreased in AD group ( P<0.05). In AD group, FC in SMN was positively correlated with total Tau and phosphorylated-Tau181 in CSF ( P<0.05); FC between VN and PCC was positively correlated with total Tau in CSF ( P<0.05). CSF Aβ 1-42 was positively correlated with FC alterations in aDMN and VN, but negatively correlated with FC in FPN ( P<0.05). Conclusion:In AD patients, characteristic changes in FC within and between multiple brain networks are noted, which are related to changes of Tau protein and Aβ 1-42 in CSF.

Objective:To analyze the clinical characteristics of patients of chronic active Epstein-Barr virus infection (CAEBV) with intestinal involvement misdiagnosed as inflammatory bowel disease (IBD).Methods:A retrospective analysis was conducted on the clinical characteristics, laboratory results, digestive endoscopic findings, histological results, treatment and prognosis of 10 patients with CAEBV intestinal involvement who were misdiagnosed as IBD and treated at the Department of Hematology, Beijing Friendship Hospital, Capital Medical University from February 2019 to November 2022. Epstein-Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Results:Among the 10 patients with CAEBV, eight were males and two were females. Seven patients had been misdiagnosed as ulcerative colitis and three misdiagnosed as Crohn′s disease. The median age of onset was 36 years (ranged from 26 to 52 years), and the median time from onset to CAEBV diagnosis was 18.5 months (ranged from 2.0 to 96.0 months). The main clinical characteristics of these patients included fever >38.5 ℃ in 10 cases, diarrhea in seven cases, abdominal pain in seven cases, abdominal lymph node enlargement in six cases and hematochezia in seven cases. Six patients primarily presented with gastrointestinal symptoms, and seven patients had involvement of extraintestinal organs, three patients developed hemorrhagic shock due to gastrointestinal bleeding. The laboratory findings included anemia in seven cases, elevated erythrocyte sedimentation rate in six cases, decreased natural killer cell activity in five cases, and elevated ferritin in three cases. Epstein-Barr virus (EBV) DNA were detected in the peripheral blood mononuclear cells (PBMCs) of nine patients, with a median viral load of 23 000 copies/mL. Seven patients were tested positive for anti-EBV viral capsid antigen IgG and nuclear antigen 1 IgG. The main endoscopy findings were hyperemia, edema of the affected intestinal wall mucosa, which could be accompanied by erosion, multiple scattered shallow ulcers with varying sizes. There were six patients with total colon involvement. The rectum was involved in three patients, and the esophagus, gastric antrum, duodenum and small intestine were each involved in one patient. Seven patients underwent follow-up colonoscopy after diagnosis, and four cases progressed. All 10 patients showed active chronic inflammation in the histopathological examinations of their intestinal tissue, with crypt changes in four cases and granulomatous changes in one cases. The intestinal tissues of eight patients were positive for EBER staining, and EBER positive cells≥50 cells/high-power field in seven patients. Seven patients were treated with 5-aminosalicylic acid before the correct diagnosis. Five patients had not improved or progressed upon the follow-up colonoscopy. Two patients died of uncontrolled massive hemorrhage of digestive tract.Conclusions:The clinical, endoscopic and pathological findings of patients with CAEBV intestinal involvement lack specificity. For IBD patients initially diagnosed accompanied by fever and evidence of extraintestinal organ involvement, it is recommended to simultaneously detect EBV DNA in PBMCs and blood plasma, EBER in intestinal tissue, and identify the main EBV-infected cells in peripheral blood and/or tissue, to distinguish CAEBV.

Objective:To investigate the predictive value of the ratio of tricuspid annulus plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) in the progression of heart failure with reduced ejection fraction (HFrEF) patients.Methods:A total of 172 patients with HFrEF in the First Affiliated Hospital of Zhengzhou University from January to December 2022 were prospectively selected. All participants underwent routine echocardiography, the routine cardiac ultrasound parameters, left atrial volume index (LAVi), right ventricular fractional area change (RVFAC) were measured. The ratio of early diastolic velocity E peak of the mitral valve orifice to the early diastolic mean velocity e′ of the mitral valve annulus (E/e′) and TAPSE/PASP were calculated. The online quantitative analysis software of the ultrasound instrument were used to obtain the left ventricular global longitudinal strain (LVGLS), left atrial reservior strain (LASr), left atrial conduit strain (LAScd), left atrial contraction strain (LASct), right ventricular global systolic strain (RVGLS), and right ventricular free wall strain (RVFWS). According to the median of TAPSE/PASP, the patients were divided into TAPSE/PASP≥0.50 mm/mmHg group(group 1, 85 cases) and TAPSE/PASP<0.50 mm/mmHg group(group 2, 87 cases). The endpoint events were recorded. The differences of the above parameters in two groups were compared, the correlation analysis was used to analyze the correlations between myocardial mechanical parameters and TAPSE/PASP. The Kaplan-Merier method was used to draw survival curves, and the Log-rank method was used to compare the differences in survival curves in the two groups. The univariate and multivariate Cox regression models were used to analyze the predictive value of TAPSE/PASP for end-point events.Results:There were no significant differences in age, gender, body mass index, complications and left ventricular end-diastolic volume (LVEDV) between the two groups (all P>0.05). Compared with group 1, patients in group 2 showed a significant decrease in RVFAC and TAPSE (all P<0.05), while the LAVi, left ventricular end-systolic volume (LVESV), right ventricular end-diastolic diameter (RVDd-base), E/e′ and PASP were increased (all P<0.05), the absolute values of LVGLS, LASr, LASct, RVGLS, and RVFWS were significantly decreased (all P<0.05). Correlation analysis showed that LVGLS, LASr, RVGLS, RVFAC and 6-min walking distance were linearly correlated with TAPSE/PASP ( r/ rs=-0.176, 0.181, -0.496, 0.472, 0.421; all P<0.05). The follow-up time was (11.71±1.80) months, and the incidence of death events in group 2 (28.73%) was higher than that in group 1 (10.61%), with a significant difference ( P<0.05). The results of multivariate Cox regression analysis showed that TAPAE/PASP was one of the independent predictive factors for endpoint events in HFrEF patients, with adjusted HR: 0.306, 95% CI=0.141-0.663, P=0.003. Conclusions:TAPSE/PASP can monitor the progression of chronic heart failure and is one of the independent predictive factors, providing a new reference indicator for clinical diagnosis and treatment.

OBJECTIVE: To compare the effectiveness of robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open freehand TLIF for the treatment of single-level degenerative lumbar spondylolisthesis (DSL) and analyse the influence on postoperative adjacent segmental degeneration (ASD). METHODS: The clinical data of 116 patients with L _4、5 DLS who were admitted between November 2019 and October 2021 and met the selection criteria were retrospectively analyzed. According to the surgical methods, they were divided into the robotic group (45 cases, who underwent robot-assisted MIS-TLIF) and the open group (71 cases, who underwent open freehand TLIF). There was no significant difference in baseline data such as gender, age, body mass index, DLS Meyerding grading, and preoperative Pfirrmann grading, Weishaupt grading, L _{3, 4} intervertebral disc height (DH), L _{3, 4} intervertebral mobility, sagittal parameters [including pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT)], and Cage height ( P>0.05). The grade of facet joint violation (FJV) by pedicle screws on the superior articular process was assessed postoperatively. Sagittal parameters, L _{3, 4} DH, L _{3, 4} DH loss, and L _{3, 4} intervertebral mobility were measured preoperatively and at last follow-up in order to determine whether ASD occurred. Based on the occurrence of postoperative ASD, logistic regression analysis was used to identify the risk factors for ASD after TLIF. RESULTS: Patients in both groups were followed up 21-47 months, with a mean of 36.1 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The occurrence of postoperative FJV was significantly better in the robotic group than in the open group ( P<0.05). At last follow-up, the difference in the change values of sagittal parameters PI, PT, SS, and LL was not significant when comparing the two groups of patients ( P>0.05); the change values of L _{3, 4} DH and L _{3, 4} DH loss in the robotic group were smaller than those in the open group, and the change value of L _{3, 4} intervertebral mobility was larger than that in the open group, and the differences were significant ( P<0.05). At last follow-up, ASD occurred in 8 patients (17.8%) in the robotic group and 35 patients (49.3%) in the open group, and the difference in ASD incidence between the two groups was significant ( P<0.05). logistic regression analysis showed that open surgery, preoperative Pfirrmann grading Ⅳ-Ⅴ, preoperative Weishaupt grading ≥2, and postoperative FJV grading ≥1 were risk factors for the development of ASD after TLIF ( P<0.05). CONCLUSION Compared with traditional open surgery, orthopedic robot-assisted MIS-TLIF in the treatment of single-level DLS can more accurately insert pedicle screws, reduce the loss of DH and the occurrence of FJV, and effectively reduce the incidence of mid-postoperative ASD. Preoperative disc and synovial joint degeneration in adjacent segments, nonrobotic-assisted minimally invasive therapy, and FJV are risk factors for ASD after TLIF.
Humans ; Spinal Fusion/methods* ; Spondylolisthesis/surgery* ; Lumbar Vertebrae/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Robotic Surgical Procedures/methods* ; Male ; Treatment Outcome ; Female ; Intervertebral Disc Degeneration/surgery* ; Retrospective Studies ; Postoperative Complications/etiology* ; Risk Factors ; Middle Aged

Objective:To study the correlations of hippocampal subfield volumes with cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) patients.Methods:Forty-nine patients with cognitive impairment, including 30 AD patients and 19 non-AD patients, were recruited in Department of Neurology, Drum Tower Clinical College, Nanjing University of Chinese Medicine from May 2017 to December 2021. Concentrations of Aβ 1-42, total tau protein and phosphorylated tau protein in CSF were analyzed by enzyme-linked immunosorbent assay (ELISA). Volumes of 12 hippocampal subfields were calculated using FreeSurfer image analysis. Differences of clinical data, neuropsychological scores and CSF biomarker concentrations between the 2 groups were compared. Partial correlation was performed to analyze the correlations of volumes of hippocampal subfields with CSF biomarker concentrations. Results:AD patients had significantly lower Mini-mental State Examination (MMSE) scores and Aβ 1-42 concentration in CSF than non-AD patients ( P<0.05); AD patients had significantly lower volumes of the right hippocampal parasitulum, dentate gyrus and CA4 than non-AD group ( P<0.05); the right parasubiculum volume was negatively correlated with CSF Aβ 1-42 ( r=-0.445, P=0.023) and positively correlated with CSF P-tau ( r=0.393, P=0.047) in AD patients. Volumes of left hippocampus tail, parasubiculum, CA1, molecular layer, dentate gyrus, CA3 and CA4 were negatively correlated with CSF total tau ( P<0.05). No significant correlation was noted between hippocampal subfield volumes and CSF biomarker concentrations in non-AD patients. Conclusion:Some right hippocampal subfields in AD patients atrophy compared with those in non-AD patients with cognitive impairment; the right parasubiculum may play a compensatory role in disease process, while volumes of the left hippocampus decreased with increased CSF total tau.

Objective:To explore the value in differentiating Borrmann Ⅳ type gastric cancer (BT4-GC) from gastric diffuse large B-cell lymphoma (DLBCL) using a nomogram based on CT texture analysis (CTTA) and morphological characteristics.Methods:From June 2011 to December 2020, a total of 60 patients with BT4-GC and 24 patients with DLBCL were retrospectively collected in Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University. Morphological characteristics were evaluated, including major location, long axis range, circumferential range, mucosal line status, and perigastric enlarged lymph nodes. CTTA parameters were calculated using venous CT images with a manual region of interest. The morphological characteristics and CTTA parameters between BT4-GC and DLBCL were compared by χ 2 test, Fisher exact test or Mann-Whitney U test. The multivariate binary logistic regression analysis was used to filter factors into the diagnostic model and construct a nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of CTTA parameters and the diagnostic model in differentiating BT4-GC from DLBCL. Results:For morphological characteristics, mucosal line status showed a significant difference between BT4-GC and DLBCL (χ 2=12.99, P<0.001). For CTTA parameters, 16 parameters showed significant differences between BT4-GC and DLBCL (all P<0.05). The area under the ROC curve (AUC) of 16 CTTA parameters in differentiating BT4-GC from DLBCL was 0.662-0.833. Percentile 90 showed the highest AUC of 0.833 (95%CI 0.736-0.906). The mucosal line status (OR 4.82, 95%CI 1.21-19.25, P=0.026) and percentile 90 (OR 1.09, 95%CI 1.04-1.15, P=0.001) were brought into the diagnostic model and constructed a nomogram. The AUC of the model in differentiating BT4-GC from DLBCL was 0.898 (95%CI 0.813-0.953), sensitivity was 0.833, and specificity was 0.817. Conclusions:The nomogram based on CTTA percentile 90 and morphological characteristics mucosal line status can effectively distinguish BT4-GC from DLBCL and shows high diagnostic efficacy.

Leukocyte differentiation antigens (LDAs) play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 (leucine rich repeat-containing 25) was predicted to have a role in the function of myeloid cells by a large-scale "omics" data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia (AML) cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid (ATRA)-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia (APL; AML-M3, FAB classification) cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced terminal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.
Antigens, Differentiation ; immunology ; metabolism ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Granulocytes ; cytology ; drug effects ; immunology ; metabolism ; Humans ; Leukocytes ; cytology ; drug effects ; immunology ; metabolism ; Membrane Proteins ; antagonists & inhibitors ; immunology ; metabolism ; RNA, Small Interfering ; pharmacology ; Tretinoin ; pharmacology

Objective?To investigate the path relationship between subjective well being of nurses in operating room, social support and career status, so as to provide reference for the training and management of specialist nurses. Methods?General Well-being Scale, Social Support Rating Scale, Career Status Assessment Scale were used in the investigation. From June to December 2016, a total of 175 specialist nurses of operating room were selected from 3 Class Ⅲ Grade A hospitals in He'nan Province. Results?The score of subjective well-being of the 175 nurses was (8.93±2.34); the score of social support was (41.32±5.63); and the total score of Career Status Assessment Scale was (82.17±9.97). The subjective well-being of operating room nurses and social support were both positively correlated with career status (r=0.258, 0.325; P＜ 0.01). Path analysis showed that subjective well being and social support had a positive predictive effect on career status, and the path coefficients were 0.36 and 0.41 respectively. Conclusions?Higher subjective well being of the operating room nurses and more social support can promote the benign development of the nurses' career.

Objective To monitor the dynamic changes of radiation-induced parotid damage using T2 ? mapping.Methods Thirty-four patients with nasopharyngeal carcinoma (NPC)were enrolled.All patients underwent T1 WI,T2 WI and T2 ? mapping for bilateral parotid glands at pre-RT (2 weeks before radiotherapy),mid-RT (5 weeks after the beginning of radiotherapy)and post-RT (4 weeks after the completion of radiotherapy).Parotid MR parameters,mean radiation dose and xerostomia degrees of the patients at different time points were recorded.Furthermore,nine healthy volunteers were enrolled,who undergone T2 ? mapping twice with an interval of 4 weeks in order to analyze the reproducibility of T2 ? value.Results From pre-RT to mid-RT and post-RT,parotid volume decreased [atrophy rates,(25.34±11.33)％ and (25.74±9.93)％,respectively]and T2 ? values decreased [change rates,(-5.63±8.86)％ and (-4.81±10.67)％, respectively]significantly (all P < 0.01 ).Parotid normalized T1 signal intensity decreased significantly from pre-RT to post-RT [change rate,(-7.43±10.61)％,P =0.007],and the change rate was correlated inversely with mean radiation dose significantly (r =-0.646, P <0.001).Parotid volume and T2 ? value changed correspondingly with xerostomia degrees of the patients during radiotherapy.Parotid MR parameters showed excellent reproducibility (intraclass correlation coefficient,0.843 -0.993).Conclusion The dynamic changes of radiation-induced parotid damage in patients with NPC can be noninvasively evaluated by routine MRI and T2 ? mapping.