Objective To compare the dosimetric differences in the heart and its substructures between two hybrid plans for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. Methods A total of 46 patients with early-stage left-sided breast cancer who underwent hypofractionated whole-breast radiotherapy were randomly selected. Two hybrid radiotherapy plans were used, including hybrid intensity-modulated radiotherapy (H_IMRT) and hybrid volumetric-modulated arc therapy (H_VMAT). The heart and its substructures were contoured, including left anterior descending (LAD), left ventricle (LV), right coronary artery (RCA), and right ventricle (RV). The heart and substructure doses, as well as monitor units, were compared between H_IMRT and H_VMAT. Results Both hybrid plans met the clinical requirements. H_IMRT significantly outperformed H_VMAT for the heart (V₁₀, V₃₀, and D_mean), LAD (V₃₀, V₄₀, D_max and D_mean), LV (V₁₀, V₂₀ and D_mean), RCA (D_max, D_mean), and RV (V₅, V₁₀, D_mean) (P < 0.001). Additionally, H_IMRT was significantly superior to H_VMAT for heart V₅, LAD V₂₀, and RV V₂₀ (P = 0.005, 0.035 and 0.037). For LAD (V₁₅, V₄₀) and LV (V₅, V₂₅), H_IMRT was slightly better than H_VMAT, and the difference was not statistically significant. Conclusion Both H_IMRT and H_VMAT hybrid radiotherapy plans are suitable for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. H_IMRT is slightly better than H_VMAT in dose sparing for the heart and its substructures.

Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

OBJECTIVE: To investigate the clinical value of hemoglobin to serum creatinine ratio (Hb/SCr) combined with blood uric acid (SUA) in predicting in-hospital mortality after emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: The clinical data of AMI patients who underwent emergency PCI in the First Affiliated Hospital of Kangda College of Nanjing Medical University from January 2017 to December 2021 were retrospectively analyzed. The general information, underlying medical history, blood routine, liver and kidney function, blood coagulation routine, SUA and other indicators were collected from patients. The primary composite endpoint was defined as in-hospital death, including in-hospital all-cause death during PCI and 15-day post-procedure hospitalization. Multivariate Logistic regression was used to analyze factors associated with in-hospital death after emergency PCI in patients with AMI. Multivariate Logistic regression was used to analyze the independent related factors and construct a risk prediction model. The Hosmer-Lemeshow method and receiver operator characteristic curve (ROC curve) were used to test the goodness of fit and predictive effect of the model and correlates, respectively. RESULTS: A total of 1 976 patients were enrolled, 92 died in hospital and 1 884 survived. SUA was higher in the death group than that in the survival group (μmol/L: 476.88±132.04 vs. 354.87±105.31, P < 0.01), and the Hb/SCr ratio was significantly lower than that in the survival group (13.84±5.48 vs.19.20±5.74, P < 0.01). Pearson analysis showed a linear negative correlation between SUA and Hb/SCr ratio (r = -0.502, P < 0.01). Logistic regression risk model analysis finally included age [odds ratio (OR) = 0.916], Hb/SCr ratio (OR = 0.182), white blood cell count (WBC, OR = 2.733), C-reactive protein (CRP, OR = 3.611), SUA (OR = 4.667), blood glucose (Glu, OR = 2.726), homocysteine (Hcy, OR = 2.688) 7 factors to construct a risk prediction model, which were independent correlation factors for in-hospital death in AMI patients after emergency PCI (all P < 0.05). Hosmer-Lemeshow test verified the fitting effect of the model, and the result showed P = 0.447. The area under the ROC curve (AUC) of the model for predicting in-hospital death in AMI patients after emergency PCI was 0.764 [95% confidence interval (95%CI) was 0.712-0.816, P = 0.001]. When the cut-off value was 0.565 8, the sensitivity was 70.7%, the specificity was 70.2%, and the Yoden index was 0.410. When Hb/SCr ratio+SUA, SUA, Hb/SCr ratio, Hb and SCr were used to predict in-hospital death in AMI patients after emergency PCI, the AUC of Hb/SCr ratio+SUA was the largest, which was 0.810. When the optimal cut-off value was -0.847, the sensitivity was 77.7%, the specificity was 74.5%, and the Youden index was 0.522. CONCLUSIONS Age, SUA, Hb/SCr ratio, WBC, CRP, Glu, and Hcy are independent risk factors for in-hospital death after emergency PCI in AMI patients. The lower the Hb/SCr ratio and the higher the SUA at admission, the higher the risk of in-hospital death after emergency PCI in AMI patients. Hb/SCr ratio combined with SUA has a higher predictive value for in-hospital death after emergency PCI in AMI patients than single index, which is helpful for early identification of high-risk patients.
Humans ; Hospital Mortality ; Uric Acid ; Creatinine ; Percutaneous Coronary Intervention ; Retrospective Studies ; Myocardial Infarction/therapy* ; Prognosis

Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

Objective? To summarize the nursing experience for 6 patients receiving wireless pacemaker implantation. Methods? The nursing experience for 6 patients who received wireless pacemaker implantation for the first time in Beijing Anzhen Hospital, Capital Medical University from August to October 2018. The nursing highlights included preoperative nursing, operative nursing, postoperative monitoring, nursing, follow-up and education. Results? 2 of the 6 patients sustained atrial fibrillation combined with long pause, and 4 sustained atrionector lesion combined with incidental long pause. The threshold value and perception of pace-making was sound and the impedance was ideal during operation. No complication was found during and post operation. The surgical time for implanting wireless pacemakers was short and the patients' appearance was not affected. Their mental burden was relatively light. Nursing procedures were simpler than the those for traditional pacemakers. Conclusion? Wireless pacemakers reduce airbag and wire-related complications and is promising in clinical use. But nursing experience needs to be observed clinically and summarized.

Objective To investigate the effect of hyperoside on proliferation and killing activity of NK cells against pancreatic cancer PANC1 cells in vitro,and explore its potential mechanism.Methods Peripheral blood mononuclear cells of healthy donors were isolated,NK cells were induced with medium contained with IL-2 and different concentrations of hyperoside (0.3,1.6,8,40 and 200 μg/ml) for 12 days.Cell viability was observed by trypan blue staining.Phenotype and perforin,granzyme B expression of NK cells were detected by flow cytometry.Killing activity of NK cells against PANC1 cells were analyzed with lactate dehydrogenase (LDH) releasing method.Results The proportion of NK cells in control group and experimental group treated with different concentration of hyperoside both reached about 80％,respectively.The proliferation of CDs-CD56 + NK cells treated by hyperoside at 0.3,1.6 and 8 μg/ml was (93.76 ±8.77),(106.67 ± 12.35) and (118.50 ± 11.51) times,respectively,which were significantly higher than (73.70 ± 9.43) times of the control group.The expressions of perforin in NK cells treated with hyperoside at 1.6,8 and 40 μg/ml were significantly higher than those of the control group [(82.34 ± 2.90) ％,(89.15 ±3.54) ％,(81.78 ± 2.81)％ vs (72.93 ± 2.06)％].The expressions of granzyme B in NK cells treated with hyperoside at 1.6 and 8 μg/ml were significantly higher than those of the control group [(87.30 ± 1.70) ％,(92.16 ±3.05)％ vs (82.35 ±2.73)％].The killing activity of NK cells against PANC1 cells treated by hyperoside at 1.6 and 8 μg/ml was significantly higher than those of the control group [(63.18 ± 3.77)％,(65.34 ± 4.97) ％ vs (52.16 ± 5.48) ％].The differences were statistically significant (all P ＜ 0.05).Conclusions Hyperoside could promote the proliferation of NK cells at certain concentrations and maybe enhance the killing effect against pancreatic cancer PANC1 cells through up-regulating the expression of perforin and granzyme B in NK cells.

Objective To explore the efficacy and clinical value of texture analysis of conventional MRI image for the preoperative classification of meningiomas. Methods The MR images of 101 meningioma cases were retrospectively analyzed, all of them underwent routine MRI before operation, and confirmed by surgery and pathology,of whom 81 cases in WHO Ⅰ,19 cases in Ⅱand 1 case in Ⅲ.The maximum diameter of the tumor in MRI images was outlined as ROI by the Image J software.The histograms and grey-level co-occurrence matrix(GLCM)were used to measure the texture parameters,such as maximum value,minimum value,standard deviation(SD),skewness,kurtosis,angular second moment,contrast,inverse different moment, entropy, correlation and so on, and compared with postoperative pathological grading results.The independent sample t test or the Mann-Whitney U test was used to compare the difference of the histogram and the gray level co-occurrence matrix parameter of the MRI images between low-grade and high-grade meningiomas. ROC curves for statistically significant parameters were used to confirm their efficacy in predicting the preoperative grade of meningiomas.Results (1)In histogram parameters,the SDs of T2WI,FLAIR,ADC(SDT2WI,SDFLAIR,SDADC)of low grade meningioma were 14.764(10.928,17.932),9.753 (7.385,13.618) and 12.171 (9.138,19.691), the high grade meningiomas were 19.252 (13.580,25.715), 13.568 (8.936,17.108) and 16.636 (13.166,21.498), respectively. The difference between the two groups was statistically significant(Z values were-2.863,-2.250,-2.247,P respectively 0.004,0.024,0.025).The skewness values (SkeADC, SkeFLAIR) of ADC sequence and FLAIR sequence of low-grade meningiomas were 1.377 ± 1.172 and-1.327 ± 0.930, respectively, and the high-grade meningiomas were 2.503 ± 1.613 and-0.827±0.834,respectively.The differences between the two groups were statistically significant (t values were-2.196,-3.129, P values were 0.002,0.030, respectively). (2) In the GLCM parameters, entropy (EntT1WI, EntT2WI, EntFLAIR, EntADC) of the enhanced T1WI, T2WI, FLAIR and ADC sequences of low grade meningiomas were 6.881(6.174,7.305),6.534±0.598,6.019±0.588,6.040±0.588,high-grade meningiomas were 7.079 (6.742,7.739), 7.014 ± 0.514,6.370 ± 0.703,6.576 ± 0.450, respectively. And the difference between the two groups was statistically significant (Z=-2.007, t values were-3.294,-2.327,-3.245, P values were 0.045,0.001,0.022,0.002,respectively).(3)The ROC curves of EntADCand SkeADCwere plotted, and the area under the curve(AUC)was 0.768 and 0.710,respectively.Combined EntADC,SkeADCand EntT2WI were the best for the classification of meningiomas,and AUC was 0.799.Conclusion Texture analysis can provide more quantification information, which can be more accurately distinguishing high grade meningiomas and low grade meningiomas before surgery.

Objective To evaluate the vasoactive-inotropic score(VIS) as a predictor of outcome in children following surgery for congenital heart disease.Methods A retrospective chart review of 472 children undergoing cardiac surgery with bypass.VIS values were calculated during the first 72 postoperative hours,and the maximum and mean scores in the first,second and third 24 postoperative hours [VIS (24max),VIS (24mean),VIS (48max),VIS (48mean),VIS (72max),VIS (72mean)] were also recorded.Chi-test,t-test,and ROC curves were performed for the association between VIS and the clinical outcomes.Results ROC analysis indicated the VIS (24max) was strongly associated with poor outcomes (AUROC =0.919,P =0.000).And the high V IS (24max) defi ned as 19.5 and above,which may lead poor outcomes (J =0.70).When the interplay between a range of factors was controlled,only lactate and VIS(24max) was related to the prognosis.Conclusion Maximum VIS calculated in the first 24 hours[VIS(24max)] after PICU admission was strongly and significantly associated with clinical outcomes in children after cardiac surgery.The greater the VIS,the worse the illness,the poorer the outcome,the higher the mortality.