Objective To construct SpyCatcher-mi3 nanoparticle vaccine delivery vectors,evaluate their role in enhancing the immunogenicity of the ovalbumin CD8+T-cell epitope peptide,OVA257-264,and determine its protective effect in a model which mice were immunized and subcutaneously challenged with E.G7-OVA tumor cells.Methods SpyCatcher-mi3 proteins were expressed by E.coli and purified by affinity chromatography and anion exchange chromatography sequentially.OVA257-264-SpyTag peptide was obtained by synthesis.The OVA257-264-mi3 nanoparticles were produced by the SpyTag/SpyCatcher system.The toxicity of OVA257-264-mi3 was evaluated using hemolysis assay,CCK-8 assay and mouse experiment.A total of 42 female SPF-grade C57BL/6 mice(6～8 weeks old,18～20 g)were randomly divided into OVA257-264-mi3,OVA257-264,and control groups,with 14 mice in each group.Then the mice in each group were immunized on days 0,14 and 28.In 14 d after the last immunization,the amounts of spot-forming cells(SFCs,indicating IFN-γ secreting cells in splenic lymphocytes)were determined using ELISpot assay to evaluate their immunogenicity.After the immunized mice were subcutaneously implanted with E.G7-OVA tumor cells,the antitumor effect of the vaccine in prophylactic xenograft tumor model was evaluate by observing tumor volumes with a caliper and tumor growth with MRI.Results Both SpyCatcher-mi3 and OVA257-264-mi3 could be self-assembled to form homogeneous and stable nanoparticles,with an average particle size of about 43.8 and 91.3 nm,respectively.The OVA257-264-mi3 was safe for in vitro and in vivo toxicity evaluation.The number of IFN--y secreting cells per 1 × 106 splenic lymphocytes reached 253 in the OVA257-264-mi3 group of mice,significantly higher than that in the OVA257-264 group and the Control group(P＜0.05).The tumor volume of mice in the OVA257-264-mi3 group was about 151.1 mm3 on day 22,which was significantly smaller than that of the OVA257-264 group and the Control group(P＜0.05),and the survival rate during the observation period reached 60％,which was significantly higher than that of the OVA257-264 groups(P＜0.05).Conclusion Nanoparticle vaccine OVA257-264-mi3 is successfully constructed,and it shows enhancing effect on the immunogenicity of the antigen epitope peptide,and exerts protective effect on prophylactic xenograft tumor model,providing a theoretical basis for the research of tumor neoantigen vaccines.

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
Humans ; Pregnancy ; Female ; Hypertension, Pregnancy-Induced/diagnosis* ; Retrospective Studies ; Pre-Eclampsia/epidemiology* ; Risk Factors ; Incidence

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.
Female ; Humans ; Middle Aged ; Adolescent ; Young Adult ; Adult ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; Retrospective Studies ; Case-Control Studies ; Breast/pathology* ; Breast Neoplasms/pathology*

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK⁺ patients while 53(15-73) years of the 30 ALK^- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult

Objective To investigate the patency rate and restenosis after percutaneous transluminal angioplasty (PTA) for the treatment of arteriovenous fistula (AVF) and arteriovenous graft (AVG) stenosis in dialysis patients. Methods The patients who were successfully treated by PTA for the first time in the blood purification center of the 2nd Affiliated Hospital of Nanjing Medical University from January 2016 to June 2017, including 71 cases of AVF in the forearm, 52 cases of AVF in the upper arm and 59 cases of AVG were recorded. The data of different stenosis parts were analyzed before and after treatment and followed up for 12 months. The initial patency rate and assisted-PTA patency rate were observed at 3 months, 6 months, 9 months, and 12 months after ultrasound interventional therapy, and the initial patency time for patients who needed to reintervention among all types of pathways were recorded. Results The initial patency rates at 3 months, 6 months, 9 months and 12 months after ultrasound interventional therapy were 98.59％, 90.14％, 71.93％, 54.93％ respectively in forearm AVF, 90.38％, 65.38％, 42.31％, 32.69％ respectively in upper arm AVF, 91.53％, 32.20％, 6.78％, 1.69％ respectively in AVG, and the PTA-assisted patency rates were 98.59％, 97.18％, 95.77％, 94.37％ respectively in forearm AVF, 92.31％, 86.54％, 84.62％, 80.77％respectively in upper arm AVF, 100.00％, 98.31％, 96.61％, 93.22％ respectively in AVG, while the initial patency time was (8.99 ± 3.54) months in forearm AVF, (6.33 ± 3.01) months in upper arm AVF, (4.80 ± 1.40) months in AVG respectively. Conclusions Ultrasound can comprehensively evaluate the function of peripheral vascular access, guide PTA treatment, and evaluate treatment outcomes. Ultrasound intervention therapy has best initial patency rate for forearm AVF stenosis. The prognosis of upper arm AVF stenosis PTA is relatively poor due to the easy cephalic stenosis. Although AVG has a short interval of restenosis, it can achieve a better long-term patency rate through regular intervention with ultrasound intervention.

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

BACKGROUNDThere are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events.

METHODSAll consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups.

RESULTSNine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3-8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group.

CONCLUSIONSDuring a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.

Aged ; Coronary Artery Bypass ; Coronary Artery Disease ; physiopathology ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Stroke Volume

OBJECTIVETo investigate the stability and three-dimensional movements of the atlantoaxial joint after artificial atlanto-odontoid joint (AAOJ) arthroplasty by comparing with a conventional method.

METHODSAfter anterior decompression, 24 human cadaveric spinal specimens of C0-C3 were randomly divided into two groups: Group A receiving artificial AAOJ arthroplasty; Group B experiencing anterior transarticular screw (ATAS) fixation. Two groups underwent flexibility test in intact and instrumented states. Rotational angle of the C0-C3 segments was measured to study the immediate stability and function of anterior decompression with AAOJ arthroplasty compared with the intact state and ATAS fixation.

RESULTSCompared with the intact state, anterior decompression with AAOJ arthroplasty resulted in a significant decrease in the range of motion (ROM) and neutral zone (NZ) during flexion, extension and lateral bending (P less than 0.05); however, with regard to axial rotation, there was no significant difference in ROM and NZ (P larger than 0.05). Compared with anterior decompression with ATAS fixation, anterior decompression with AAOJ arthroplasty during flexion, extension and lateral bending, significant difference was found in ROM and NZ (P larger than 0.05); however, as for axial rotation, there was a significant increase in ROM and NZ (P less than 0.05).

CONCLUSIONThe self-designed AAOJ has an excellent biomechanical performance, which can restore excellent instant stability and preserve the movement of the atlantoaxial joint.

Adult ; Arthroplasty ; methods ; Atlanto-Axial Joint ; physiopathology ; surgery ; Biomechanical Phenomena ; Bone Plates ; Bone Screws ; Cadaver ; Decompression, Surgical ; Female ; Humans ; Joint Instability ; physiopathology ; surgery ; Male ; Middle Aged ; Range of Motion, Articular ; physiology

OBJECTIVETo investigate the difference in intracellular calcium ion [Ca2+]i concentration in prostate smooth muscle cells (PSMCs) between SD rat models of chronic abacterial prostatitis (CAP) and normal controls, and to evaluate the role of [Ca2+]i concentration in CAP.

METHODSWe established CAP models in SD rats using purified prostate protein and Freund's complete adjuvant, cultured in vitro and then purified the PSMCs of both the CAP models and normal controls. Continuous dynamic scanning was performed under the laser confocal scanning microscope after incubation of the cells with FLUO-3AM.

RESULTSThe fluorescence intensities of [Ca2+]i in the PSMCs were 80.39 +/- 9.00 and 27.95 +/- 10.04 in the CAP models and normal controls, respectively, with statistically significant differences between the two groups (P < 0.01).

CONCLUSIONThe concentration of [Ca2+]i increased in the PSMCs of the CAP rat models, which might enhance the constriction of PSMCs and subsequently increase the sensibility to pain and cause lower abdominal pain.

Animals ; Calcium ; metabolism ; Cells, Cultured ; Chronic Disease ; Male ; Myocytes, Smooth Muscle ; metabolism ; Prostate ; metabolism ; Prostatitis ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.