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简介：AbstractBackground:Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.Methods:We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.Results:Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).Conclusion:Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

简介：AbstractImportance:The process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.Objective:To assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).Methods:Fifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI , while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.Results:For group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).Interpretation:For DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

简介：AbstractBackground:The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19.Methods:Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups.Results:Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ2 = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ2 = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir.Conclusions:The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

简介：AbstractBackground:The relationship between macrocirculation and microcirculation remains controversial. The loss of coherence between microcirculation and macrocirculation has already been found in late-stage sepsis shock. The objective of this study was to determine the earliest possible time of detecting the loss of coherence between microcirculation and macrocirculation in early-stage endotoxemic shock.Methods:We randomized 24 female New Zealand white rabbits into two groups: endotoxemic shock group (n = 14) and control group (n= 10). Rabbits in the endotoxemic shock group were equipped with arterial and venous catheters and received an intravenous infusion of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg over 10 min). Rabbits in the control group received the same dose of saline infusion. Microcirculatory perfusion parameters were assessed in the sublingual mucosa using sidestream dark-field video microscopy. Systemic hemodynamics and blood lactate levels were measured at baseline and over a 120-min period.Results:Ninety minutes after completing LPS infusion, all animals in the endotoxemic shock group developed a hypodynamic septic condition, characterized by low cardiac output and increased systemic vascular resistance; 120 min after completing LPS infusion, the mean arterial pressure decreased by 25% (P = 0.01), confirming ongoing endotoxemic shock. However, significant decreases in sublingual microcirculatory parameters of small vessels (microvascular flow index, perfused vessel density, and proportion of small perfused vessels) were observed 30 min after completing LPS infusion (P = 0.01, for all), and threshold decreases of 30% were found 60 min after completing LPS infusion (P = 0.001, for all) in the endotoxemic shock group. Lactate levels significantly increased to more than 2 mm/L at 90 min and more than 4 mm/L at 120 min in the endotoxemic shock group (P = 0.02 and P = 0.01, respectively).Conclusions:Changes in microcirculatory perfusion precede changes in macrocirculation and lactate levels in a rabbit model of endotoxemia shock. Microcirculation, macrocirculation, and oxygen metabolism are distinct in early-stage endotoxic shock.

简介：AbstractBackground:High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease (ESRD). IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults. Here, we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization (MR) approach.Methods:For observational analysis, 108 IgAN patients, 30 lupus nephritis (LN) patients, 50 minimal change disease (MCD) patients, and 206 healthy controls were recruited from April 2014 to April 2015. Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records. For MR analysis, we further included 1686 IgAN patients. The missense variant methylenetetrahydrofolate reductase C677T (rs1801133) was selected as an instrument, which was genotyped by TaqMan allele discrimination assays.Results:Majority of IgAN patients (93.52%, 101/108) showed elevated levels of plasma homocysteine (>10 μmol/L). Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients (median: 18.32 vs. 11.15 μmol/L, Z = －5.29, P < 0.01) and in healthy controls (median: 18.32 vs. 10.00 μmol/L, Z = －8.76, P < 0.01), but comparable with those in LN patients (median: 18.32 L vs. 14.50 μmol/L, Z = －1.32, P = 0.19). Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio (22.22% vs. 51.85% vs. 70.37% vs. 70.37%, χ2 = 14.29, P < 0.01), serum creatinine (median: 77.00 vs. 100.00 vs. 129.00 vs. 150.00 μmol/L, χ2 = 34.06, P < 0.01), estimated glomerular filtration rate (median: 100.52 vs. 74.23 vs. 52.68 vs. 42.67 mL·min－1·1.73 m－2, χ2 = 21.75, P < 0.01), systolic blood pressure (median: 120.00 vs. 120.00 vs. 125.00 vs. 130.00 mmHg, χ2 = 2.97, P = 0.05), diastolic blood pressure (median 80.00 vs. 75.00 vs. 80.00 vs. 81.00 mmHg, χ2 = 11.47, P < 0.01), and pathologic tubular atrophy and interstitial fibrosis (T) (T0/T1/T2: 62.96%/33.33%/3.70% vs. 29.63%/40.74%/29.63% vs. 24.00%/48.00%/28.00% vs. 14.81%/37.04%/48.15%, χ2 = 17.66, P < 0.01). The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12 (P < 0.01). MR estimates showed causal positive effects of homocysteine on serum creatine (β = 0.76, P = 0.02), systolic blood pressure (β = 0.26, P = 0.02), diastolic blood pressure (β = 0.20, P = 0.01), and pathologic T lesion (β = 0.01, P = 0.01) in IgAN.Conclusions:By observational and MR analyses, consistent results were observed for associations of plasma homocysteine with serum creatinine, blood pressures, and pathologic T lesion in IgAN patients.

简介：AbstractBackground:After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC.Methods:Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics.Results:A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17–106 months). There was no significant correlation between the infiltrate density of CD4+, CD8+, CD20+, and CD68+ lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4+-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8+-TILs (DFS: P = 0.018) and low CD20+-TILs (OS: P = 0.042). Further analysis showed that patients with CD4+/CD20+ ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8+/CD20+ ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis.Conclusions:Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.

简介：AbstractBackground:The detrimental outcomes of right ventricular pacing on left ventricular electromechanical function ultimately result in heart failure, a phenomenon termed pacing-induced cardiomyopathy (PICM) in clinical research. This study aimed to validate prognostic factors that can be used to identify patients with higher susceptibility to progress to the stage of cardiomyopathy before pacemaker implantation.Methods:This observational analysis enrolled 256 patients between January 2013 and June 2016, 23 (8.98%) of whom progressed to PICM after 1 year of follow-up. A Cox proportional hazard model was used to analyze the prognostic factors associated with PICM. Dose-response analysis was used to evaluate the relationship between significant indicators in multifactor analysis and PICM.Results:The mean values of left ventricular ejection fraction before and after pacemaker implantation in 23 patients diagnosed with PICM were 62.3% and 42.7%, respectively. Univariate analysis showed that sex, atrio-ventricular block, paced QRS duration, and ventricular pacing percentage were significantly associated with PICM. In the multivariate analysis, male sex (hazard ratio: 1.20, 95% confidence interval [CI]: 1.09-1.33, P < 0.005), paced QRS duration (hazard ratio: 1.95 per 1 ms increase, 95% CI: 1.80-2.12, P < 0.001), and ventricular pacing percentage (hazard ratio: 1.65 per 1% increase, 95% CI: 1.51-1.79, P < 0.001) were independent prognostic factors associated with the development of PICM. The ventricular pacing percentage and paced QRS duration level defined by the dose-response analysis were positively associated with PICM (P < 0.05).Conclusions:Our findings indicated that paced QRS duration and ventricular pacing percentage were the most sensitive prognostic factors for PICM.