[Clinicopathological features and prognosis of early-onset gastric cancer: a large-scale retrospective real-world study].

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

[Application of seamless phase â ¡/â ¢ design in vaccine clinical trials].

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

[Clinical implications of Naples prognostic scores in patients with resectable Siewert type II-III adenocarcinoma of the esophagogastric junction].

Objective: To evaluate the clinical value of preoperative Naples prognostic scores (NPS) in patients with resectable Siewert type II-III esophagogastric junction adenocarcinoma (AEG). Methods: In this retrospective observational study we collected and analyzed relevant data of patients with Siewert Type II-III AEG treated in the Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital from January 2014 to December 2018. NPS were calculated using preoperative albumin concentration, total cholesterol concentration, neutrophil/lymphocyte ratio, and lymphocyte/monocyte ratio and used to allocate patients into three groups: NTS-0 (0 points), NTS-1 (1-2 points) and NTS-2 (3-4 points). Kaplan-Meier was used to calculate disease-free survival (DFS) and overall survival (OS) in each NPS group and the log-rank test to compare these groups. Univariate and multivariate survival analyes were performed using the Cox regression model. Time-dependent receiver operating characteristic curves were constructed to compare the relationships between four commonly used tools for evaluating inflammatory responses and nutritional status:NPS, systemic inflammatory response scores, nutrient control status (CONUT), and prognostic nutrition index (PNI). Results: The study cohort comprised 221 patients with AEG of median age 63.0 (36.0-87.0) years. There were 190 men (86.0%) and 31 women (14.0%). As to pTNM stage, 47 patients (21.3%) had Stage I disease, 68 (30.8%) Stage II, and 106 (48.0%) Stage III. One hundred and forty-seven patients (66.5%) had Siewert Type II disease and 74 (33.5%) Siewert type III. There were 45 patients (20.4%) in the NPS-0, 142 (64.2%) in the NPS-1 and 34 (15.4%) in the NPS-2 groups. Higher NPS scores were significantly associated with older patients (χ²=5.056, P=0.027) and higher TNM stages (H=5.204,P<0.001). The median follow-up was 39 (6-105) months; 16 patients (7.2%) were lost to follow-up. The median OS in the NPS-0, NPS-1, and NPS-2 groups were 78.4, 63.1, and 37.0 months, respectively; these differences are statistically significant (P=0.021). Univariate and multivariate Cox regression analysis identified the following as independently and significantly associated with OS in patients with Siewert Type II-III: TNM stage (Stage II: HR=2.182, 95%CI: 1.227-3.878, P=0.008; Stage III: HR=3.534, 95%CI: 1.380-6.654, P<0.001), tumor differentiation (G3: HR=1.995, 95%CI: 1.141-3.488, P=0.015), vascular invasion (HR=2.172, 95%CI: 1.403-3.363, P<0.001), adjuvant chemotherapy (HR=0.326, 95%CI: 0.200-0.531, P<0.001), NPS (NPS-1: HR=2.331, 95%CI: 1.371-3.964, P=0.002; NPS-2: HR=2.494, 95%CI: 1.165-5.341, P=0.019), SIS group (NPS-1: HR=2.170, 95%CI: 1.244-3.784, P=0.006; NPS-2: HR=2.291, 95%CI: 1.052-4.986, P=0.037), and CONUT (HR=1.597, 95% CI: 1.187-2.149, P=0.038). The median DFS in the NPS-0, NPS-1, and NPS-2 groups was 68.6, 52.5, and 28.3 months, respectively; these differences are statistically significant (P=0.009). Univariate and multivariate Cox regression analysis identified the following as independently and significantly associated with DFS in patients with Siewert Type II-III AEG: TNM stage (StageⅡ: HR=2.789, 95%CI:1.210-6.428, P=0.016; Stage III: HR=10.721, 95%CI:4.709-24.411, P<0.001), adjuvant chemotherapy (HR=0.640, 95% CI: 0.432-0.946, P=0.025), and NPS (NPS-1: HR=1.703, 95%CI: 1.043-2.782, P=0.033; NPS-2: HR=3.124, 95%CI:1.722-5.666, P<0.001). Time-dependent receiver operating characteristic curves showed that NPS was more accurate in predicting OS and DFS in patients with Siewert Type II-III AEG than were systemic inflammatory response scores, CONUT, or PNI scores. Conclusion: NPS is associated with age and TNM stage, is an independent prognostic factor in patients who have undergone resection of Siewert type II-III AEG, and is better than SIS, CONUT, or PNI in predicting survival.

Prediction of Fuhrman grade of renal clear cell carcinoma by multimodal MRI radiomics: a retrospective study.

AIM: To explore the value of multimodal magnetic resonance imaging (MRI) radiomics combined with traditional radiologist-defined semantic characteristics and conventional (cMRI) and functional MRI (fMRI) texture features in predicting Fuhrman grade of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The data of 89 patients with histopathologically proven ccRCC (low-grade, 54; high-grade, 35) were collected. Texture features were extracted from cMRI (T1- and T2-weighted imaging) and fMRI (Dixon-MRI; blood-oxygen-level dependent [BOLD]-MRI; and susceptibility-weighted imaging [SWI]) images, and the traditional characteristics (TC) were evaluated. Logistic regression analysis was performed to develop models based on TC, cMRI, and fMRI texture features for grading. Receiver operating characteristic (ROC) curve analysis and leave-group-out cross-validation (LGOCV) were performed to test the reliability of combined models. RESULTS: Two T2-weighted imaging-based, two Dixon_W-based, one Dixon_F-based, one BOLD-based, and three SWI-based texture features, and three TC were extracted for feature selection. TC, cMRI, fMRI, cMRI+fMRI, cMRI+TC, fMRI+TC, and cMRI+fMRI+TC models were constructed. The AUC of the cMRI+fMRI+TC model for differentiating high- from low-grade ccRCC was 0.74, with 81.42% accuracy, 75.93% sensitivity, and 91.43% specificity. The fMRI+TC model exhibited a performance similar to that of the cMRI+fMRI+TC model (p>0.05). The areas under the curve (AUCs) of the fMRI+TC and cMRI+fMRI+TC models were significantly higher than those of the other five models (all p<0.05). For the cMRI+fMRI+TC model, the mean accuracy was 85.40% after 100 LGOCV for the test sets. CONCLUSION: Multimodal MRI radiomics combined with TC, cMRI, and fMRI texture features may be a reliable quantitative approach for differentiating high-grade ccRCC from low-grade ccRCC.

[The comparison of modified ESUR score and Mehralivand grade based on biparametric MRI for assessing extracapsulare extension in prostate cancer].

Objective: To compare the value of the modified European Society of Urogenital Radiology (ESUR) score and Mehralivand grade based on biparametric MRI (bpMRI) in the assessment of extracapsular extension (ECE) in patients with prostate cancer (PCa). Methods: Data of 235 patients with postoperative pathology confirmed PCa, who underwent preoperative 3.0 T bpMRI examinations between March 2019 and March 2022 in the First Affiliated Hospital of Soochow University were retrospectively evaluated, including 107 ECE positive and 128 ECE negative cases, aged [M (Q1, Q3)] [71 (66, 75)] years. Reader 1 and 2 assessed the ECE using the modified ESUR score and Mehralivand grade, and the receiver operating characteristic curve and Delong test were used to evaluate the performance of the two scoring methods. Then, the statistically significant variables were included in multivariate binary logistics regression analysis to obtain the risk factors, which were combined with the scores of reader 1 to establish combined models. The assessment ability of the two combined models and the two scoring methods were compared subsequently. Results: The AUC of Mehralivand grade in reader 1 were higher than that of the modified ESUR score in reader 1 and 2 [0.746 (95%CI: 0.685-0.800) vs 0.696 (95%CI: 0.633-0.754) and 0.691 (95%CI: 0.627-0.749), both P<0.05]. The AUC of Mehralivand grade in reader 2 was higher than that of the modified ESUR score in reader 1 and 2 [0.753 (95%CI: 0.693-0.807) vs 0.696 (95%CI: 0.633-0.754) and 0.691 (95%CI: 0.627-0.749), both P<0.05]. The AUC of the combined model 1 based on the modified ESUR score and the combined model 2 based on Mehralivand grade were higher than that in the separate modified ESUR score [0.826 (95%CI: 0.773-0.879) and 0.841 (95%CI: 0.790-0.892) vs 0.696 (95%CI: 0.633-0.754), both P<0.001], and also higher than that in the separate Mehralivand grade [0.826 (95%CI: 0.773-0.879) and 0.841 (95%CI: 0.790-0.892) vs 0.746 (95%CI: 0.685-0.800), both P<0.05]. Conclusion: Based on bpMRI, the Mehralivand grade showed better diagnostic performance for assessing ECE preoperatively in patients with PCa than the modified ESUR score. The combination model of scoring methods and clinical variables can further enhance the diagnostic certainty in the assessment of ECE.

Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia.

Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2-20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.

[Endoscopic diagnosis and treatment of early colorectal cancer and precancerous lesions: current status and future prospects].

Early detection of colorectal cancer and precursor lesions under colonoscopy, and timely and optimal treatment remain the crucial means for reducing colorectal cancer-related deaths. In this article, we focused on the hot spots in recent years, reviewed the progress of endoscopic diagnosis and treatment of serrated lesions and inflammatory bowel disease (IBD)-related dysplasia, the application of endocytoscopy and the management of early colorectal cancer/precancerous lesions, and provided new prospects for future studies.

[Review of risk evaluation scores for benign end stage liver diseases recipients].

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.

[Review of risk evaluation scores for benign end stage liver diseases recipients].

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.

[Preliminary application of the Asia-Pacific colorectal screening score combined with the quantitative fecal occult blood in colorectal neoplasia screening].

To evaluate the efficacy of the Asia-Pacific colorectal screening (APCS) score combined with the quantitative fecal immunochemical test in colorectal neoplasia screening. Subjects who appointment to receive colonoscopy were recruited from August 2017 to May 2019 in the digestive endoscopy center. Before the colonoscopy, all subjects were scored by the Asia Pacific colorectal cancer screening scoring system and measured by quantitative fecal immunochemical test (QFIT). The detection rates of colorectal neoplasia were compared to evaluate the efficacy of the combined assay in colorectal neoplasia screening between APCS score and QFIT. A total of 1 420 subjects were enrolled in this study, APCS score medium-risk (MR) and high-risk (HR) groups were 847 (59.7%) and 573 (40.4%) and 26 cases (1.8%) of colorectal cancer, 196 cases (13.8%) of advanced adenoma, and 395 cases (27.8%) of non-advanced adenoma were detected. With the combination of APCS score and QFIT, participants were classified into 4 groups high-risk with positive QFIT result group G1, high-risk with negative QFIT result group G2, medium-risk with positive QFIT group G3, medium-risk negative QFIT group G4. The prevalence of colorectal neoplasia was 64.3%, 16.4%, 55.0%, and 9.8%, respectively. The prevalence of advanced neoplasia in high-risk with QFIT results was significantly higher than that in other 3 groups. HR and positive QFIT were the indicators for further colonoscopy, and MR with FIT negative group could postpone colonoscopy and conduct annual QFIT follow-up. The combination of APCS score and QFIT for colorectal neoplasia screening can reduce unnecessary colonoscopy, improve colonoscopy compliance and screening efficiency, and has important clinical significance and promotion value in colorectal tumor screening.

[Consensus and controversy on accurate diagnosis and treatment of resectable gastric cancer].

Gastric cancer is a common malignant tumor of digestive tract in China. Precise, minimally invasive and standardized surgical operation is an important part of comprehensive treatment for gastric cancer. In recent years, indications for minimally invasive surgery have been expanding, research on precision surgery has been deepening, and the standardized surgical quality evaluation and control system has been improving. Accurate diagnosis and staging, multi-disciplinary comprehensive diagnosis and treatment model, enhanced recovery after surgery and whole-process management of nutrition support and other aspects have been comprehensively developed. A number of Chinese expert consensus has been issued, which is conducive to the rapid and good recovery of patients, achieving the double benefits of improving the quality of life and prolongation of survival. However, the precise treatment of complex conditions is still full of controversy. This consensus is formulated to facilitate the standardization of the diagnosis and treatment of gastric cancer.

[The optimal thresholds of the quantitative fecal immunochemical test for opportunistic screening of colorectal neoplasia].

Objective: To investigate the significance of quantitative fecal immunochemical test (FIT) for opportunistic screening of colorectal neoplasia, and to propose the most optimal thresholds to improve the screening level of early colorectal neoplasia. Methods: The opportunistic screening participants were recruited from the Department of Gastroenterology & GI Endoscopy Center of the Seventh Medical Center of PLA General Hospital, and stool sample was collected before colonoscopy and the quantitative FIT was analyzed by OC-MICRO analysator for each patient. We assessed test performance in detecting colorectal neoplasia (advanced adenoma and CRC)with different thresholds on sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: A total of 1 448 objects were enrolled in this study, including 714 male (49.3%)and 734 female (50.7%).All participants were classified according to the result of colonoscopy and pathology, and 242 cases of colorectal neoplasia were found, containing 157 advanced adnoma and 85 colorectal cancer. The FIT threshold increased from 50 µg/L to 200 µg/L, while the positivity rate dropped from 11.5% to 8.6% and the sensitivity in detecting colorectal neoplasia dropped from 47.9% to 38.8%. However, the specificity increased from 96.8% to 98.2% and the positive predictive value increased from 82.3% to 87.0%.The miss rate of colorectal cancer increased from 11.8% (n=10) to 17.6% (n=15) along with the increase in FIT thresholds, but the miss rate of 100 µg/L and 150 µg/L was the same as 12.9% (n=11). Conclusions: Quantitative FIT,which is simple and fast,with the threshold of 100 µg/L for opportunistic screening, has a high sensitivity and specificity for the diagnosis of colorectal neoplasia,and is an important index in screening and diagnosis of colorectal neoplasia.

[Effect of human stromal vascular fraction gel on the treatment of patients with skin depressed scar and its mechanism].

Objective: To observe content of cytokine in human stromal vascular fraction gel (SVF-GEL) and effect of SVF-GEL on biological behaviors of epidermal and dermal cells in vitro and clinical efficacy of SVF-GEL. Methods: (1) SVF-GEL was prepared using liposuction aspirates harvested from females who received abdomen liposuction in author's unit. SVF-GEL (1 mL) and high-glucose Dulbecco's modified eagle medium (DMEM, 1 mL) were respectively cultured for 24 h with high-glucose DMEM containing 10% fetal calf serum, 10 g/L penicillin, and 10 g/L streptomycin, denoted as SVF-GEL group and negative control group, with 6 samples in each group. Content of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in the supernatant was determined by enzyme-linked immunosorbent assay. (2) A number of 5×10(5) human skin fibroblasts (HSF) and HaCaT cells in logarithmic phase were inoculated and cultured in Transwell chambers for 12 h. All Transwell chambers containing cells were divided into SVF-GEL group (0.5 mL SVF-GEL was added for co-culture) and control group (0.5 mL high-glucose DMEM was added for co-culture), with 9 samples in each group for HSF and HaCaT cells. Scratch assay was performed after culture for 24 h, and residual scratch width was observed at post scratch hour (PSH) 0 (immediately), 24, and 48. Cell migration distance was measured at PSH 24 and 48. After culture for 24, 48, and 72 h, the number of living cell was counted using cell counter. (3) From June 2018 to June 2019, SVF-GEL was applied clinically to treat 15 patients with depressed scars on face, including 2 males and 13 females, aged 19 to 42 years. Survival condition of SVF-GEL and whether complications or not were observed 6 months after surgery. Before surgery and 6 months after surgery, depressed degree, color, and pliability of scar were compared. Vancouver Scar Scale (VSS) was employed to access color, vascularity, and pliability before surgery and 6 months after surgery, and total score was calculated. The number of patients with complete satisfaction or satisfaction was counted six months after surgery. Data were processed with analysis of variance of factorial design, paired samples t test, and Wilcoxon rank sum test. Results: (1) The content of EGF in SVF-GEL group and negative control group was (316.6±12.8) and (3.4±0.6) pg/mL, and the content of VEGF in SVF-GEL group and negative control group was (568.67±12.19) and (4.93±0.16) pg/mL, with statistically significant differences between the two groups (t=48.777, 92.485, P<0.01). (2) Residual scratch widths of HSF and HaCaT in SVF-GEL group and control group were decreased gradually along with time elapse, in which those in SVF-GEL group at PSH 24 and 48 were less than those in control group. At PSH 24 and 48, cell migration distances of HSF and HaCaT in SVF-GEL group were more than those in control group (t(HSF)=-20.304, -43.516, t(HaCaT)=-15.060, -8.684, P<0.01). After culture for 24, 48, and 72 h, the number of living cell of HSF and HaCaT in SVF-GEL group was significantly more than that in control group (t(HSF)=-3.374, -6.809, -18.036, t(HaCaT)=-4.793, -6.028, -8.141, P<0.05 or P<0.01). (3) Six months after surgery, SVF-GEL grafted into patients survived well without complications, and depressed degree of scar ameliorated obviously with lightened pigmentation and softer texture as compared with before surgery. Compared with those before surgery, VSS scores of color, vascularity, and pliability, and total score of 15 patients with depressed scars on face were obviously decreased 6 months after surgery (Z=-2.06, -2.07, -2.07, t=-15.811, P<0.05 or P<0.01). One patient was satisfied with the clinical outcome, and the rest 14 patients were completely satisfied with the clinical outcomes. Conclusions: SVF-GEL contains cytokines EGF and VEGF, which can enhance cell migration ability and proliferation ability of HSF and HaCaT cells and have obvious effects on depressed scars for clinical application.

[Clonal evolution and clinical significance of trisomy 8 in acquired bone marrow failure].

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Systematic review and meta-analysis of elective and urgent late open conversion after failed endovascular aneurysm repair.

BACKGROUND: In this study, we systematically reviewed late open conversions after failed endovascular aneurysm repair (EVAR), assessed the methodologic quality of the included studies, and performed a meta-analysis on the 30-day mortality rates for urgent and elective late conversions. METHODS: Electronic databases were systematically searched for studies published up to June 2018 that focused on late open conversion of failed EVAR (ie, >30 days after the initial EVAR), reported the primary outcome of 30-day mortality rate, and distinguished the 30-day mortality rate between urgent and elective late conversions. Two independent reviewers assessed the methodologic quality of the included studies with the Methodological Index for Non-Randomized Studies. Data on baseline demographics, indication for conversion, surgical approach, and early and late mortality rates were recorded. Reported data correspond to the average or range of the means reported in the individual studies. A random-effects model was used to pool 30-day mortality rates for urgent and elective late conversion. RESULTS: There were 27 retrospective studies with a total of 791 patients available for analysis, with 617 elective and 174 urgent late conversions. The methodologic quality was mostly poor (median, 6; interquartile range, 5-7). The mean time from primary EVAR to conversion was 35.1 months (95% confidence interval [CI], 30.4-39.8 months). The most commonly explanted endografts were Excluder (W. L. Gore & Associates, Flagstaff, Ariz) in 16.2%, Talent (Medtronic, Minneapolis, Minn) in 14.5%, and AneuRx (Medtronic) in 13.7%. Nineteen other types of endografts were used in 43.3%; the type of endograft was not reported in 12.3%. A transperitoneal approach was used in a mean 74.0% of conversions (95% CI, 70.9%-77.0%), and complete endograft explantation was performed in 478 (60.4%) patients (95% CI, 57.0%-63.8%). The complication rate was 36.7% (95% CI, 27.0%-46.4%). Temporary or permanent hemodialysis after conversion was required in 3.9% of patients (95% CI, 2.6%-5.2%). The pooled estimate for the 30-day mortality rate was 2.8% (95% CI, 1.5%-4.0%; P = .726) for elective late conversions and 28.1% (95% CI, 18.9%-37.3%; P < .001) for urgent late conversions. CONCLUSIONS: Type I endoleak and rupture are the most common indications for, respectively, elective and urgent conversions. A 10 times higher 30-day mortality rate was observed for patients treated with late open conversion in an urgent vs elective setting. The 30-day mortality rate of elective late open conversions is almost comparable to that of primary elective open abdominal aortic aneurysm repair procedures. For the interpretation of the outcomes of the review, however, the methodologic quality of the available literature should be considered.

[Analysis the features of familial benign paroxysmal positional vertigo].

Objective:The family heredity of BPPV disease was preliminarily discussed in order to guide the clinical practice, prevent early and shorten the course of BPPV disease in the future. Method:Familial BPPV patients were enquired and registered in detail, including gender, age at first onset, occupation, inducing factors, symptoms, diagnosis, sleep status and clinical manifestations. Analysis of the clinical data. Result:Nine patients with idiopathic BPPV from four families had no definite pathogenic factors, accounting for 0.4% of the patients with idiopathic BPPV, including 3 males and 6 females; the age of first onset ranged from 31 to 66 years old. the course of disease ranged from 2 days to 8 years; the duration of nystagmus ranged from seconds to 1 minute. The main clinical symptoms were dizziness and visual rotation related to position transformation. Family 1, 3 and 4 patients had a history of fatigue. Family 2 patients had a predisposing factor of forced lateral decubitus due to lumbar discomfort. All patients had nystagmus lasting less than 1 minute and were single-tube involvement, all patients were canalithiasis. Different patients in the same family have different pathogenic locations. Conclusion:Familial BPPV is urgent to attract the attention of clinicians and the public. Early clinical test for suspected familial BPPV can play a role in early prevention and shorten the process of disease, so as to improve the life quality of patients.

CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP.

The maturation of dendritic cells is critical for chronic rhinosinusitis with nasal polyps (CRSwNPs), especially eosinophilic chronic rhinosinusitis with nasal polyps (EosCRSwNPs), but the regulation mechanism of dendritic cells (DCs) maturation is still unclear. We identified nasal mucosa of 20 patients with EosCRSwNP, 16 non-EosCRSwNP patients, and inferior turbinate of 14 patients with nasal septum deviation after surgery. The expression of cyclin-dependent kinase 5 (CDK5) and programmed cell death 1 ligand 1 (PD-L1) were detected by immunofluorescent, real-time quantitative PCR, and Western blot in EosCRSwNP. The level of dendritic cell maturation was detected by flow cytometry and immunofluorescence staining after CDK5 expression interference with small interfering RNA (siRNA). The expression of CDK5 and PD-L1 in EosCRSwNP nasal mucosal tissue was significantly higher than that of non-EosCRSwNP and inferior turbinate nasal mucosa tissue, and there was a positive correlation between them. Immunofluorescence staining showed that CDK5 and PD-L1 were co-localized in dendritic cells. Synergistic stimulation of dendritic cells with LPS and TNF-α promotes the maturation of dendritic cells and increases the expression of CDK5 and PD-L1. However, blocking the expression of CDK5 in dendritic cells with siRNAs leads to a blockage of cell maturation. CDK5 can regulate the expression of PD-L1, and its presence is critical for the maturation of dendritic cells. CDK5 may play an important role in the pathogenesis of CRSwNP disease.

Histopathological features of antrochoanal polyps in Chinese patients.

BACKGROUND: The pathogenesis and etiology of antrochoanal polyps (ACP) are unclear. The aim of this study is to characterize the features of inflammatory cellular infiltration, the epithelial remodeling patterns and their associations to clinical parameters in ACP. METHODS: A detailed histological study employing classic immunohistochemistry was performed. 33 ACPs, 49 classic bilateral nasal polyps (BNP) and 50 controls were obtained. The histological patterns and inflammatory cells infiltration were evaluated and analyzed for associations with clinical characteristics. RESULTS: Less severe epithelial hyperplasia and goblet cell hyperplasia were found in ACP compared to BNP. In ACP, 87.9% of cases demonstrated neutrophilia. Elevated proportions of macrophages and CD8+ T cells, and elevated infiltration of mast cells was observed. Eosinophil infiltration was found to be positively corelated with a history of asthma; macrophages proportion was analyzed to have a significantly negative correlation with epithelial hyperplasia and goblet cell hyperplasia; the infiltration of CD8+ T cell and squamous metaplasia were found to have a positive correlation. CONCLUSION: Inflammation potentially has important roles in ACP. ACP may differ in its pathogenesis from classic bilateral nasal polyps.