nd stroke onset.

With accumulating dysregulated circular RNAs(circRNAs)in pathological processes,the regulatory functions of circRNAs,especially circRNAs as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely validated.However,the collected information on experimentally validated circRNA-disease associations is only preliminary.Therefore,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary.Here,we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics.CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version.This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes.Secondly,the information of circRNA-miRNA,circRNA-miRNA-target,and circRNA-RBP interactions has been manually collected for various diseases.Thirdly,the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases.Detailed descriptions such as samples and journals have also been integrated into the updated version.Thus,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases.Finally,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 database.

Objective To evaluate the feasibility of utilizing dose-volume histogram (DVH) prediction models of organs at risk (OARs) to deliver automatic treatment planning of prostate cancer.Methods The training set included 30 cases randomly selected from a database of 42 cases of prostate cancer receiving treatment planning.The bladder and rectum were divided into sub-volumes (Ai) of 3 mm in layer thickness according to the spatial distance from the boundary of planning target volume (PTV).A skewed normal Gaussian function was adopted to fit the differential DVH of Ai,and a precise mathematical model was built after optimization.Using the embedded C++ subroutine of Pinnacle scripa,ahe volume of each Ai of the remaining validation set for 12 patients was obtained to predict the DVH parameters of these OARa,ahich were used as the objective functions to create personalized Pinnacle script.Finalla,automatic plans were generated using the script.The dosimetric differences among the original clinical plannina,aredicted value and the automatic treatment planning were statistically compared with paired t-test.Results DVH residual analysis demonstrated that predictive volume fraction of the bladder and rectum above 6 000 cGy were lower than those of the original clinical planning.The automatic treatment planning significantly reduced the V70,V60,V50 of the bladder and the V70 and V60 of the rectum than the original clinical planning (all P＜0.05),the coverage and conformal index (CI) of PTV remained unchangea,and the homogeneity index (HI) was slightly decreased with no statistical significance (P＞ 0.05).Conclusion The automatic treatment planning of the prostate cancer based on the DVH prediction models can reduce the irradiation dose of OARs and improve the treatment planning efficiency.

Objective:To evaluate the use of ulthera in carotid body tumor resectionMethods:From Jun 2004 to Jun 2019 at the First Hospital of China Medical University. Forty-three shamblin grade Ⅱ or Ⅲ patients were retrospectively assigned to ulthera assisted carotid body tumor resection (26 cases) and traditional carotid body tumor resection (17 cases).Results:In ulthera assisted group, the average tumor diameter was (4.0±0.6) cm, compared to (3.9±0.9) cm in traditional carotid body tumor surgery group, P=0.875. The operation time of the two group was respectively (117.6±39.8) min and (149.4±55.0) min ( P=0.005), blood loss (145.7±70.6) ml vs. (194.1±80.7) ml ( P=0.006), hospital stay was (16.8±7.5) d vs. (22.7±13.0) d ( P=0.017), and following-up period was between 6 and 180 months. One patient relapsed in ulthera assisted group. The postoperative complications occurred in 8 and 7 cases respectively. Conclusion:Ulthera assisted carotid body tumor resection helps shorten operation time, hospital stay and decrease intraoperative blood loss.

Objective:To evaluate the safety and feasibility of transumbilical single-port transabdominal preperitoneal hernioplasty plus cholecystectomy (SILS-TAPP+LC).Methods:The clinical data of 52 adult patients who underwent [SILS-(TAPP+LC)] from Mar, 2019 to Oct, 2021 at the Affiliated Hospital of Nantong University were retrospectively analyzed.The perioperative indicators, postoperative complications and follow-up data were analyzed.Results:All operations were successfully completed without conversion to open or multi-port laparoscopic surgery.The duration of surgery was (49.2 ± 7.5) min. Three patients experienced gallbladder rupture, and there was no bladder or intestinal injury during the surgery.During the 20-24 months of postoperative follow-up period,4 patient developed seroma in the postoperative period, 4 patients complained foreign body sense in the inguinal region, 3 patients reported chronic pain, but no other complications, such as biliary fistula, recurrence, mesh infection, or trocar hernia, were observed.Conclusion:SILS-(TAPP+LC) was a safe and feasible approach associated with little postoperative pain and rapid recovery.

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.
Aged ; Aged, 80 and over ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Critical Illness ; Immunity ; Retrospective Studies ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects* ; Viral Vaccines/adverse effects*

Child ; Developmental Disabilities/genetics* ; Frameshift Mutation ; Humans ; Seizures/genetics* ; Seizures, Febrile/genetics* ; Semaphorins/genetics*

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.