Fizeau drag in graphene plasmonics.

Dragging of light by moving media was predicted by Fresnel1 and verified by Fizeau's celebrated experiments2 with flowing water. This momentous discovery is among the experimental cornerstones of Einstein's special relativity theory and is well understood3,4 in the context of relativistic kinematics. By contrast, experiments on dragging photons by an electron flow in solids are riddled with inconsistencies and have so far eluded agreement with the theory5-7. Here we report on the electron flow dragging surface plasmon polaritons8,9 (SPPs): hybrid quasiparticles of infrared photons and electrons in graphene. The drag is visualized directly through infrared nano-imaging of propagating plasmonic waves in the presence of a high-density current. The polaritons in graphene shorten their wavelength when propagating against the drifting carriers. Unlike the Fizeau effect for light, the SPP drag by electrical currents defies explanation by simple kinematics and is linked to the nonlinear electrodynamics of Dirac electrons in graphene. The observed plasmonic Fizeau drag enables breaking of time-reversal symmetry and reciprocity10 at infrared frequencies without resorting to magnetic fields11,12 or chiral optical pumping13,14. The Fizeau drag also provides a tool with which to study interactions and nonequilibrium effects in electron liquids.

Reductive Oxy-Nazarov Cyclization toward Expedient Construction of a Cyclopenta[1,2-b]pyrrolo[1,2-a]azepine Ring System: Formal Total Syntheses of Stemonamine and Cephalotaxine.

Formal total syntheses of stemonamine and cephalotaxine bearing the core cyclopenta[1,2-b]pyrrolo[1,2-a]azepine ring skeleton were achieved. The general synthetic strategy in the synthesis features the reductive oxy-Nazarov cyclization as key step, leading to the versatile construction of N-substituted spiro quaternary stereogenic centers from readily available starting materials.

Incremental yield of whole-genome sequencing over chromosomal microarray analysis and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis.

OBJECTIVES: First, to determine the incremental yield of whole-genome sequencing (WGS) over quantitative fluorescence polymerase chain reaction (QF-PCR)/chromosomal microarray analysis (CMA) with and without exome sequencing (ES) in fetuses, neonates and infants with a congenital anomaly that was or could have been detected on prenatal ultrasound. Second, to evaluate the turnaround time (TAT) and quantity of DNA required for testing using these pathways. METHODS: This review was registered prospectively in December 2022. Ovid MEDLINE, EMBASE, MEDLINE (Web of Science), The Cochrane Library and ClinicalTrials.gov databases were searched electronically (January 2010 to December 2022). Inclusion criteria were cohort studies including three or more fetuses, neonates or infants with (i) one or more congenital anomalies; (ii) an anomaly which was or would have been detectable on prenatal ultrasound; and (iii) negative QF-PCR and CMA. In instances in which the CMA result was unavailable, all cases of causative pathogenic copy number variants > 50 kb were excluded, as these would have been detectable on standard prenatal CMA. Pooled incremental yield was determined using a random-effects model and heterogeneity was assessed using Higgins' I2 test. Subanalyses were performed based on pre- or postnatal cohorts, cases with multisystem anomalies and those meeting the NHS England prenatal ES inclusion criteria. RESULTS: A total of 18 studies incorporating 902 eligible cases were included, of which eight (44.4%) studies focused on prenatal cohorts, incorporating 755 cases, and the remaining studies focused on fetuses undergoing postmortem testing or neonates/infants with congenital structural anomalies, constituting the postnatal cohort. The incremental yield of WGS over QF-PCR/CMA was 26% (95% CI, 18-36%) (I2 = 86%), 16% (95% CI, 9-24%) (I2 = 85%) and 39% (95% CI, 27-51%) (I2 = 53%) for all, prenatal and postnatal cases, respectively. The incremental yield increased in cases in which sequencing was performed in line with the NHS England prenatal ES criteria (32% (95% CI, 22-42%); I2 = 70%) and in those with multisystem anomalies (30% (95% CI, 19-43%); I2 = 65%). The incremental yield of WGS for variants of uncertain significance (VUS) was 18% (95% CI, 7-33%) (I2 = 74%). The incremental yield of WGS over QF-PCR/CMA and ES was 1% (95% CI, 0-4%) (I2 = 47%). The pooled median TAT of WGS was 18 (range, 1-912) days, and the quantity of DNA required was 100 ± 0 ng for WGS and 350 ± 50 ng for QF-PCR/CMA and ES (P = 0.03). CONCLUSION: While WGS in cases with congenital anomaly holds great promise, its incremental yield over ES is yet to be demonstrated. However, the laboratory pathway for WGS requires less DNA with a potentially faster TAT compared with sequential QF-PCR/CMA and ES. There was a relatively high rate of VUS using WGS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Establishment and validation of a prediction model for early-stage epithelial ovarian cancer based on LASSO regression].

Objective: To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. Methods: A total of 509 cases ovarian mass patients who underwent surgical treatment in Tianjin Medical General Hospital from January 2018 to March 2023 were retrospectively analyzed. The patients were randomly divided into modeling group [n=356, M(Q1,Q3) for age were 43 (31, 61) years] and internal validation group [n=153, age 42 (31, 60) years] by 7∶3 ratio. In addition, 86 patients [age 44 (33, 61) years] who underwent surgical treatment for ovarian mass in Tianjin Medical University General Hospital from April to November 2023 were collected as external validation group. The variables were screened by LASSO regression. The nomogram model was established and plotted by multivariate logistic regression. Internal and external validation were then conducted. The model performance and clinical applicability were evaluated using receiver operating characteristic (ROC) curve, calibration curve and decision curve. Results: Five variables including age (OR=1.040,95%CI:1.000-1.050,P=0.002), carbohydrate antigen 125 (CA125) (OR=1.001, 95%CI: 1.000-1.010, P=0.017), human epididymis protein 4 (HE4) (OR=1.020, 95%CI: 1.000-1.030, P=0.002), carbohydrate antigen 199 (CA199) (OR=1.001, 95%CI:1.000-1.020, P=0.023) and lactate dehydrogenase (LDH) (OR=1.020, 95%CI: 1.010-1.022, P=0.001) were screened as risk factors for early-stage epithelial ovarian cancer. The nomogram model was constructed based on these above five risk factors to predict early-stage epithelial ovarian cancer. ROC curves showed the area under curve (AUC) were 0.915(95%CI:0.910-0.932)for modeling group, 0.891(95%CI:0.874-0.905) for internal validation group, and 0.924(95%CI:0.907-0.942) for external verification. The calibration curves and clinical decision curves showed the model exhibited good consistency and clinical practicability. Conclusions: The nomogram model built includes age, CA125, HE4, CA199, and LDH. It can effectively predict early-stage epithelial ovarian cancer and has strong clinical practicability.

[Clinicopathological and genetic characteristics of congenital cystic adenomatoid malformation of lung and its associated lung cancer in adults].

Objective: To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults. Methods: A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases. Results: The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene. Conclusions: CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.

[Clinicopathological analysis of adult hepatic mesenchymal hamartoma].

Objective: To explore the clinicopathological and molecular genetic features of adult hepatic mesenchymal hamartoma (MHL). Methods: A total of five confirmed adult MHL cases diagnosed at the Pathology Department of the First Medical Center of the People's Liberation Army General Hospital between 2009 and 2022 were collected. Histomorphological observation and immunohistochemical staining were conducted. Gene detection was performed by next-generation sequencing. Results: Among the five cases, four were male and one was female, aged 46-67 years, with an average age of 56.2 years. The maximum diameter was 5.3-13.5cm, and the average diameter was 9.2cm. Tumors were generally cystic, solid, or mixed cystic-solid. Histopathologically, in four out of five cases of MHL, malignant transformation occurred, of which three cases were malignantly transformed into undifferentiated embryonal sarcoma and one case was malignantly transformed into a malignant solitary fibrous tumor. NAB2-STAT6 gene rearrangements were identified. Conclusion: Adult MHL is a rare kind of tumor with malignant potential, and it is difficult to diagnose with preoperative imaging examinations. A fine-needle biopsy is rarely used for diagnosis, but surgical resection of symptomatic or enlarged lesions is recommended to rule out the possibility of malignancy and further diagnosis. Genetic testing results revealed the complex genetic alterations in MHL, and it was found that adult MHL can malignantly transform into malignant solitary fibrous tumors. We believe that genome-wide analysis is necessary to determine the unique molecular characteristics of MHL and identify potential targets for therapeutic intervention.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

[Endovascular treatment for Stanford type B aortic dissection in Marfan syndrome patients: a series of 23 cases].

Objective: To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement. Methods: This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve. Results: Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time (M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95%CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95%CI:61.8% to 92.8%). Conclusions: TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

[Surgical strategies and efficacy analysis for aortic dissection complicating intractable mesenteric artery ischemia].

Objective: To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia. Methods: This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded. Results: Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%. Conclusions: Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.

[Clinical characteristics and follow-up analysis of 63 cases of silicosis complicated with cavity-pulmonary tuberculosis].

Objective: To investigate the clinical characteristics and prognosis of silicosis complicated with cavity-pulmonary tuberculosis. Methods: The clinical data of 63 patients with silicosis complicated with cavity-pulmonary tuberculosis (group A) and silicosis patients (group B) admitted to Yantaishan Hospital from July 2018 to July 2022 were collected and analyzed. Results: Patients in group A were all male, and the common symptoms were cough, expectoration, chest tightness, shortness of breath, and hemoptysis. CT cavity lesions involving the lung, often occurs in the lung after the tip section, after the back section and basal segment, thick-walled cavity, may be accompanied by satellite lesions, endobronchial spread focal, pneumothorax, pleural effusion, etc. 1225 cases of group B patients haemoptysis of 59 patients, cavity in 3 patients, haemoptysis and/or cavity rate was lower than that in group A, the difference was statistically significant (P<0.05) . In group A, CT reexamination 6-24 months after anti-tuberculosis treatment showed that 52 cases (82.5%) had cavity reduction/healing, 8 cases (12.7%) had recurrence, and 3 cases (4.8%) had damaged lung (2 died) . Conclusion: Silicosis patients with hemoptysis and/or CT in cavity should be more vigilant about combined tuberculosis, anti-tuberculosis treatment and/or dynamic CT follow-up helps laboratory diagnosis negative patients.

[The role of intravoxel incoherent motion diffusion-weighted imaging in distinguishing diabetic nephropathy from non-diabetic renal disease in diabetic patients].

Objective: To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM). Methods: A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student's t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman's correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results: A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10-3 mm2/s vs. 7.35×10-3 mm2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score (r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score (r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion: IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.

[Diagnostic value of multiparametric MRI-based models in the assessment of extra-prostatic extension of prostate cancer].

Objective: To evaluate the diagnostic value of multiparametric magnetic resonance imaging (mpMRI) based models in the assessment of extra-prostatic extension (EPE) of prostate cancer. Methods: This retrospective study included 168 consecutive men with prostate cancers [aged 48 to 82 (66.6±6.8) years] who underwent radical prostatectomy and preoperative mpMRI examinations at the First Medical Center of the PLA General Hospital from January 2021 to February 2022. According to European Society of Urogenital Radiology (ESUR) score, EPE grade and mEPE score, all cases were independently evaluated by two radiologists, with disagreement reviewed by a senior radiologist as the final result. The diagnostic performance of each MRI-based model for pathologic EPE prediction was assessed using receiver operating characteristic curve (ROC), and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. The weighted Kappa test was used to evaluate the inter-reader agreement of each MRI-based model. Results: A total of 62 (36.9%) prostate cancer patients had pathologic confirmed EPE after radical prostatectomy. The AUC of ESUR score, EPE grade and mEPE score for predicting pathologic EPE were 0.836 (95%CI: 0.771-0.888), 0.834 (95%CI: 0.769-0.887) and 0.785 (95%CI: 0.715-0.844), respectively. The AUC of ESUR score and EPE grade were both superior to that of mEPE score with significant differences (all P<0.05), while there was no significant difference between the ESUR score and EPE grade models (P=0.900). EPE grading and mEPE score had good inter-reader consistency, with weighted Kappa values of 0.65 (95%CI: 0.56-0.74) and 0.74 (95%CI: 0.64-0.84), respectively. The inter-reader consistency of ESUR score was moderate, and the weighted Kappa value was 0.52 (95%CI: 0.40-0.63). Conclusion: All MRI-based models showed good preoperative diagnostic value in predicting EPE, among which the EPE grade resulted in more reliable performance with substantial inter-reader agreement.

[Study on the relationship between indexes of different abnormal weight and dyslipidemia in adults in Beijing City].

Objective: To analyze the relationship and consistency between indexes of different abnormal weight and dyslipidemia in adults in Beijing City. Methods: From August to December of 2017, 4 975 residents aged 18 to 79 years old in 5 districts of Beijing were randomly selected as subjects by using a multi-stage stratified cluster sampling method. Questionnaire, physical examination and laboratory tests were conducted. The prevalence of overweight/obesity, high body fat rate, central obesity, and high waist-to-height ratio was calculated. Partial correlation was used to analyze the correlation of blood lipid with body mass index (BMI), body fat rate, waist circumference and waist-height ratio. Logistic regression analysis for complex sampling was used to analyze the relationship between indexes of different abnormal weight and dyslipidemia after controlling for relevant risk factors, including age, sex, smoking status, drinking, insufficiency intake of vegetable and fruit, physical inactivity. Kappa value was computed to analyze the consistency between indexes of different abnormal weight. Results: The weighted prevalence of dyslipidemia was 30.48%, and it was higher in men than that in women (40.16% vs. 20.52%, P<0.01). The weighted rate of overweight/obesity, high body fat rate, central obesity, and high waist-to-height ratio was 56.65%, 47.52%, 42.48% and 59.45%, respectively. BMI, body fat rate, waist circumference and waist-to-height ratio were positively correlated with the level of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and negatively correlated with high-density lipoprotein cholesterol. Logistic regression analysis for complex sampling showed that the high body fat rate (OR=1.67, 95%CI: 1.35-2.07), overweight/obesity (OR=1.65, 95%CI: 1.26-2.14) and high waist-to-height ratio (OR=1.46, 95%CI: 1.09-1.96) were associated with dyslipidemias. Kappa values of high body fat rate with overweight/obesity, high waist-to-height ratio and central obesity were 0.65, 0.53 and 0.58, respectively (P<0.05). Conclusion: In 2017, the prevalence of dyslipidemia in adults in Beijing City is high, especially in men. Overweight/obesity, high body fat rate and high waist-to-height ratio are associated with dyslipidemia. The high body fat rate is most associated with dyslipidemia.

[Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations].

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

[Current status and challenges of endovascular repair for Stanford type A aortic dissection].

Type A aortic dissection (TAAD) is characterized by acute onset, high mortality and high surgical risks.Although open surgery has been the first-line treatment for TAAD in current guidelines, 10% to 30% of them will accept conservative treatment due to the high risk of open surgery.In recent years, with the rapid progress of endovascular technology and the innovations of various devices, endovascular repair for TAAD has shown encouraging preliminary results.Thoracic endovascular aortic repair (TEVAR) has become the first-line treatment for complicated type B aortic dissection (TABD).By sealing the primary entry tear and promoting the remodeling of the false lumen, TEVAR is more minimally invasive and efficient compared to open repair.Compared with TBAD, TEVAR for TAAD is not fully elucidated.The primary entry tear is located in the ascending aorta, which has different pathophysiology characteristics from that in TBAD.More suitable and safe stent-graft and delivery system are needed. In terms of technology, the selection of proximal and distal landing zone and intraoperative brain protection are still the key and difficult problems. At the same time, there is a lack of mature programs in the treatment of the aortic root and the reconstruction of the aortic arch branches.

[Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans].

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

[A case of von Hippel-Lindau syndrome with optic disc pit and macular hole].

A 69-year-old female patient presented to the ophthalmology department with complaints of blurred vision in the left eye for more than 10 days. Her medical history revealed a history of right renal tumor and left pheochromocytoma, which were treated with surgical resection at an external institution. Ophthalmic examination revealed a temporal superior cup-shaped optic disc pit in the left eye, along with a macular hole approximately 1/5 the size of the optic disc diameter in the macular region. Additionally, peripheral retinal examination at the 6 o'clock and 11 o'clock positions showed vascular tumors, each approximately 1.5 times the size of the optic disc diameter. Based on the patient's medical history, fundus findings, and auxiliary examination results, a diagnosis of macular hole in the left eye, optic disc pit in the left eye, and Von Hippel-Lindau (VHL) syndrome was established. Subsequently, the patient underwent left vitrectomy and macular hole repair surgery, leading to an improvement in visual acuity.

[The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy].

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0

Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects.

OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.

Caloric restriction and Roux-en-Y Gastric Bypass promote white adipose tissue browning in mice.

PURPOSE: Caloric restriction (CR) and Roux-en-Y Gastric Bypass (RYGB) are considered effective means of body weight control, but the mechanism by which CR and RYGB protect against high-fat diet (HFD)-induced obesity remains elusive. The browning of white adipose tissue (WAT) is a potential approach to combat obesity. Here we assess whether browning of WAT is involved in CR- and RYGB-treatment. METHODS: The average size of adipocytes was determined by histological analysis. Expression of thermogenic genes in both human subjects and mice were measured by quantitative real-time PCR and immunohistochemical staining. RESULTS: The average size of adipocytes was bigger, while the expression of thermogenic genes such as uncoupling protein 1 (UCP1), nuclear factor erythroid-2 like 1 (NRF1) and PPARγ coactivator-1 α (PGC1α) were lower in the WAT of obese subjects when compared to lean controls. Both CR and RYGB promoted weight and fat loss. Increment of the average adipocytes size and down-regulation of thermogenic genes were significantly reversed by both CR and RYGB in the WAT of obese mice. CONCLUSIONS: Our findings showed that CR and RYGB significantly improved high-fat diet-induced lipid accumulation by promoting the browning of WAT.