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Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. In phase 3 clinical studies, the addition of daratumumab to standard-of-care regimens consistently demonstrated a significant progression-free survival (PFS) benefit and improved depth of response, including minimal residual disease-negativity, in patients (pts) with newly diagnosed MM or RRMM. In the primary analysis of the phase 3 CASTOR study (median follow-up: 7.4 mo), D-Vd reduced the risk of disease progression or death by 61% (median PFS, not reached [NR] vs 7.2 mo; hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.28-0.53; P Methods: Eligible pts in LEPUS and CASTOR received ≥1 prior line of therapy and were randomized 2:1 in LEPUS and 1:1 in CASTOR to 8, 21-day cycles of V (1.3 mg/m2 SC) on Days 1, 4, 8, and 11, and d (20 mg, PO or IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 ± D (16 mg/kg IV) given QW for Cycles 1-3, Q3W for Cycles 4-8, and Q4W thereafter. The primary endpoint for both studies was PFS. Results: A total of 211 (D-Vd, n=141; Vd, n=70) pts in LEPUS and 498 (D-Vd, n=251; Vd, n=247) pts in CASTOR were randomized. The median (range) age was 61 (28-82) years for Chinese and 64 (30-88) years for global pts. In general, baseline characteristics were similar between Chinese and global pts and balanced between treatment arms, with the exception of median body weight (LEPUS: 67 kg; CASTOR: 76 kg). Chinese and global pts both received a median of 2 prior lines of therapy; 79% and 66% received prior V, 27% and 28% were refractory to lenalidomide, and 64% and 32% were refractory to their last prior line of therapy, respectively. After a median follow up of 8.2 months in LEPUS and 7.4 months in CASTOR, a consistent PFS benefit of D-Vd vs Vd was demonstrated in the pooled analysis set across age (60 mL/min) subgroups (Table 1). Median time to progression was also consistently prolonged with D-Vd vs Vd across pooled pt subgroups. Among response evaluable pts, D-Vd improved overall response rate, rate of very good partial response or better, and rate of complete response or better (Table 2) and prolonged median duration of response vs Vd in all pt subgroups. Additional data, including PFS2, from the pooled subgroups analysis will be presented at the meeting. The safety profile of D-Vd was generally consistent across pts in LEPUS and CASTOR. Grade 3/4 treatment-emergent adverse events (TEAEs; D-Vd/Vd) occurring at a ≥5% frequency with D-Vd vs Vd in both Chinese and global pts included thrombocytopenia (51%/37%; 45%/33%), lymphopenia (44%/29%; 10%/3%), neutropenia (16%/6%; 13%/4%), and hypertension (12%/3%; 7%/1%). 49%/38% of Chinese and 42%/34% of global pts had ≥1 serious TEAEs. TEAEs leading to treatment discontinuation occurred in 4%/3% of Chinese and 7%/9% of global pts, and TEAEs leading to death occurred in 4%/10% of Chinese and 5%/6% of global pts. Rates of infusion-related reactions (IRRs) were similar for D-Vd across studies (LEPUS: 38%; CASTOR: 45%); most occurred during the first infusion and the majority were grade 1/2. Conclusions: D-Vd demonstrated a clinical benefit, including significantly improved PFS, in pooled Chinese and global pts with RRMM who received ≥1 prior line of therapy, regardless of age, cytogenetic risk status, or renal function. The safety profile of D-Vd was consistent across all pts, and no new safety concerns were identified. These results support the use of D-Vd in Chinese pts with RRMM. Disclosures Jin: The First Affiliated Hospital of Zhejiang University: Current Employment. Spencer:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Cilag GmbH: Consultancy, Honoraria, Research Funding, Speakers Bureau. Weisel:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Honoraria. Mateos:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nooka:Adaptive Technologies: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding. Qi:Janssen: Current Employment, Current equity holder in publicly-traded company; Johnson and Johnson: Current equity holder in publicly-traded company. Sun:Janssen: Current Employment, Current equity holder in publicly-traded company. Gai:Janssen: Current Employment, Current equity holder in publicly-traded company. Liu:Janssen: Current Employment, Current equity holder in publicly-traded company. Yang:Janssen: Current Employment, Current equity holder in publicly-traded company.

Stem cell-based therapy has been suggested as a promising option for the treatment of renal ischemia-reperfusion injury (IRI). However, how to efficiently deliver stem cells remains a challenge. In the present study, we firstly proposed the utilization of kidney extracellular matrix hydrogel (ECMH) as an injectable scaffold for delivering adipose-derived mesenchymal stem cells (ad-MSCs) into ischemic kidneys. A modified strategy of decellularization and gelation was introduced to prepare the ECMH, by which the bioactive ingredients were retained as much as possible. Bioluminescence living imaging and immunofluorescence revealed that ECMH could significantly elevate the retention and survival rate of transplanted ad-MSCs in damaged kidneys and reduce their escape rate to other organs, which consequently resulted to the enhanced therapeutic effect of ad-MSCs on renal IRI. Further, in vitro evidence demonstrated that ECMH could remarkably reduce the oxidative stress and apoptosis, promote the proliferation, secretion, and epithelial differentiation of ad-MSCs, as well as facilitate cell migration while acting as a sustained-release scaffold. This study establishes an effective approach to enhance the therapeutic potential of ad-MSCs for renal IRI. Our findings suggest that ECMH derived from organs or tissues would be a promising injectable scaffold for stem cell-based therapy. STATEMENT OF SIGNIFICANCE: It remains a challenge to efficiently deliver stem cells to target tissues, which may limit the clinical application of stem cell-based therapy. In this study, we developed a modified strategy of decellularization and gelation to prepare the kidney extracellular matrix hydrogel (ECMH). In vivo and in vitro evidence indicated that the kidney ECMH could improve the retention and survival rate, as well as multiple biological functions of adipose-derived mesenchymal stem cells, thereby contributing to the histological and functional recovery of injured kidneys induced by ischemia-reperfusion. Our findings highlight the use of organs or tissues derived ECMH as a promising stem cell delivery scaffold for tissue repair.

High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the IKAROS (encoded by the IKZF1 gene) tumor suppressor. Here, we report that IKAROS regulates expression of the BCL2L1 gene (encodes the BCL-XL protein) in human B-ALL. Gain-of-function and loss-of-function experiments demonstrate that IKAROS binds to the BCL2L1 promoter, recruits histone deacetylase HDAC1, and represses BCL2L1 expression via chromatin remodeling. In leukemia, IKAROS’ function is impaired by oncogenic casein kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces IKAROS binding and recruitment of HDAC1 to the BCL2L1 promoter. This results in a loss of IKAROS-mediated repression of BCL2L1 and increased expression of BCL-XL. Increased expression of BCL-XL and/or CK2, as well as reduced IKAROS expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, increases binding of IKAROS to the BCL2L1 promoter and enhances IKAROS-mediated repression of BCL2L1 in B-ALL. Treatment with CX-4945 increases sensitivity to doxorubicin in B-ALL, and reverses resistance to doxorubicin in multidrug-resistant B-ALL. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia. These data lay the groundwork for clinical testing of a rationally designed, targeted therapy that combines the CK2 inhibitor, CX-4945, with doxorubicin for the treatment of hematopoietic malignancies.

Low‐energy shock wave (LESW) has been recognized as a promising non‐invasive intervention to prevent the organs or tissues against ischaemia reperfusion injury (IRI), whereas its effect on kidney injury is rarely explored. To investigate the protective role of pretreatment with LESW on renal IRI in rats, animals were randomly divided into Sham, LESW, IRI and LESW + IRI groups. At 4, 12, 24 hours and 3 and 7 days after reperfusion, serum samples and renal tissues were harvested for performing the analysis of renal function, histopathology, immunohistochemistry, flow cytometry and Western blot, as well as enzyme‐linked immunosorbent assay. Moreover, circulating endothelial progenitor cells (EPCs) were isolated, labelled with fluorescent dye and injected by tail vein. The fluorescent signals of EPCs were detected using fluorescence microscope and in vivo imaging system to track the distribution of injected circulating EPCs. Results showed that pretreatment with LESW could significantly reduce kidney injury biomarkers, tubular damage, and cell apoptosis, and promote cell proliferation and vascularization in IRI kidneys. The renoprotective role of LESW pretreatment would be attributed to the remarkably increased EPCs in the treated kidneys, part of which were recruited from circulation through SDF‐1/CXCR7 pathway. In conclusion, pretreatment with LESW could increase the recruitment of circulating EPCs to attenuate and repair renal IRI.

ZSM-5 zeolite was modified by Fenton's reagent, FeSO4 and H2O2 aqueous solutions using impregnation method, respectively. All these catalysts were characterized by XRD, ICP-OES, N2 adsorption-desorption, NH3-TPD, Py-FTIR and evaluated in propene oligomerization process. The results demonstrated that the framework of the parent ZSM-5 was well preserved after modification with Fenton's reagent, FeSO4 or H2O2 solutions. However, the SiO2/Al2O3 ratios for all the modified ZSM-5 samples increased due to the dealumination. Furthermore, Fe was detected in Fenton-ZSM-5 while no Fe was observed for FeSO4-ZSM-5 catalyst. The BET surface areas and total pore volumes of three modified catalysts significantly increased compared with the original ZSM-5 sample. Among them, the BET surface area of the Fenton-ZSM-5 increased by 17.86%. The increase of mesopores was probably caused by the removal of the residual organic template in the catalysts due to the generation of ·OH radicals by Fenton's reagent and H2O2. The Fenton-ZSM-5 catalyst formed new acid sites of Bronsted (B) and Lewis (L) with little change in the total calculated amount, which significantly changed the B/L ratio. Compared with the parent ZSM-5, the Fenton-ZSM-5 catalyst exhibited the best activity and stability for propene oligomerization reaction. The initial propene conversion and diesel selectivity were as high as 98.3% and 92.4%, respectively, and kept at >80% and >82% for about 24 h, respectively.

Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR−, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

Waste C1 gases as alternatives to pure CO2 can potentially facilitate the practical application of microbial electrosynthesis (MES) for chemicals production and further decrease the total cost. Thi...

Background We used bioinformatic tools to dichotomize 157 non-M3 AML patients from the TCGA dataset based on the presence or absence of TP53 mutations, and screened out a key gene related to TP53 mutation for future analysis. Methods DEGs were analyzed by R package “DESeq2” and then run GSEA, GO enrichment, KEGG pathway and PPI network. Hub genes were selected out according to MCC. Log-rank (Mantel–Cox) test was used for survival analysis. Mann–Whitney U’s nonparametric t test and Fisher’s exact test was used for continuous and categorical variables respectively. p value Results TNFRSF4 was final screened out as a key gene. Besides TP53 mutation (p = 0.0118), high TNFRSF4 was also associated with FLT3 mutation (p = 0.0102) and NPM1 mutation (p = 0.0024). Elevated TNFRSF4 was significantly related with intermediate (p = 0.0004) and poor (p = 0.0011) risk stratification as well as relapse statute (p = 0.0099). Patients with elevated TNFRSF4 expression had significantly shorter overall survival (median survival: 2.35 months vs. 21 months, p TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs (p = 0.0377) and MDS patients (EB-1, 2; p = 0.0017). Conclusions Elevated TNFRSF4 expression was associated with TP53, FLT3 and NPM1 mutation as well as poor clinical outcome. TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs and MDS (EB-1, 2) patients. TNFRSF4 is need for future functional and mechanistic studies to investigate the role in non-M3 AML.

OBJECTIVE We aimed to investigate whether Chinese endoscopists without narrow-band imaging (NBI) experiences could achieve high accuracy in the real-time diagnosis of colorectal polyps using NBI International Colorectal Endoscopic (NICE) classification after web-based training. METHODS Altogether 15 endoscopists from five centers with no NBI experiences followed a short, web-based training program on the NICE classification and took web-based test. Their performances were compared with 15 matched experienced endoscopists with no NBI experience who received no NBI training. These 15 trained endoscopists then made real-time diagnoses of colorectal neoplasia. A logistic regression was used to assess potential predictors of diagnostic performance. RESULTS Compared with those who received no training, trained endoscopists achieved comparable overall accuracy (85.3% vs 83.1%, P = 0.408) and accuracy at a high-confidence level (87.0% vs 86.0%, P = 0.670), but had a higher confidence rate (86.1% vs 83.7%, P = 0.004) for the diagnosis of neoplasia. Real-time diagnostic accuracy, sensitivity and specificity were 94.3% (95% confidence interval [CI] 91.5%-96.2%), 96.2% (95% CI 93.4%-97.9%) and 85.3% (95% CI 74.8%-92.1%) at high-confidence level. The high-confidence level was the strongest predictor of real-time diagnostic accuracy (odds ratio 12.66, P

This paper presents a novel electromechanical brake (EMB) with automatic wear adjustment function, which has been ignored in most previous studies. With the aim of investigating the parameter characteristics of the EMB system and analyzing the proposed function, the mathematical models of the DC motor, motor friction, worm drive, ball screw and load are established in MATLAB/Simulink. The differences between the simulation and the experiment under step, triangular wave, square wave and sinusoidal input signals are discussed. The parameter characteristics of clamping force-motor current and clamping force-ball screw displacement are obtained, which also verifies that the established model is correct. The results demonstrate that the automatic wear adjustment function of the new EMB could guarantee that the brake stroke and response time remain consistent across each braking manoeuvre.

Objective: The present study aimed to investigate the function of lncRNA CASC15 (cancer susceptibility candidate 15) in hepatocellular carcinoma (HCC), as well as its regulatory roles in SOX4 expre...

Purpose: The early BCR-ABL1 reduction had the prognostic impact of the chronic-phase chronic myeloid leukemia (CML-CP) patients. This study was to find a more precise early prognosis index at 3 months in the patients with newly diagnosed CML-CP, especially for the patients with BCR-ABL1IS >10%. Methods: We retrospectively analyzed the data of 79 newly diagnosed CML-CP patients from October 2013 to April 2017. All patients took imatinib regularly and continuously and monitored BCR-ABL1 transcript level at baseline and 3, 6, 9, 12, 18 months after starting imatinib treatment. Results: Among the 44(55.7%) patients with BCR/ABL1IS ≤10% at 3 months after imatinib treatment, 12(27.3%) cases did not achieve major molecular response (MMR) at 12 months, and 7(14.9%) patients with the halving time BCR-ABL1 transcript ≤40 days failed to achieve MMR at 12 months. However, approximately twenty-six percent of the patients with BCR-ABL1IS >10% still obtained MMR. Moreover, the patients with BCR-ABL1IS ≤10% and halving time ≤40 days had a significantly better MMR than that of the patients with the BCR-ABL1IS ≤10% and halving time >40 days (88.6% versus 11.1%, P 10% and halving time >40 days rarely achieved MMR at 12 months. Conclusion: These data indicated that the halving time of BCR-ABL1 transcript was also an important prognostic factor as that of the BCR-ABL1IS. Combined observations of these two prognosis indexes are more accurate predictor for the long-term molecular response, especially for the CML-CP patients with BCR-ABL1IS >10%, and which is helpful for TKI switching as early as possible to improve patients' survival and reduce drug costs.

The C-X-C chemokine receptor 4 (CXCR4) has been reported to be involved in several cancer related processes. The current study was designed to investigate the role of CXCR4 in human kidney cancer and to unveil the underlying molecular mechanisms. The results showed the expression of CXCR4 to be significantly (P

Yiguan Qian,* Yang Li,* Ke Chen,* Ning Liu, Xi Hong, Di Wu, Zheng Xu, Liuhua Zhou, Luwei Xu, Ruipeng Jia, Yu-Zheng Ge Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruipeng Jia; Yu-Zheng Ge, Department of Urology, Nanjing First Hospital, Nanjing Medical University Nanjing, Jiangsu, People’s Republic of China, Tel +86-15850675660, Email ruipengj@163.com; geyuzheng@njmu.edu.cnBackground: Polo-like kinase 1 (PLK1) belongs to polo-like kinases family and affects cell cycles. However, the role of PLK1 in some malignant tumors remains unclear.Methods: To obtain a comprehensive view of PLK1 expression patterns, public databases including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, the Genotype-Tissue Expression, and human cell landscape databases were employed. The correlation of PLK1 expression with prognosis, immune infiltrations, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methylation was examined. Besides, we validated the results of clear cell renal cell carcinoma (ccRCC) in two cohorts, with quantitative real-time PCR, Western blot, and loss-of-function experiments.Results: By mining public datasets, we discovered that PLK1 expression in tumor tissues and cancer cell lines displayed heterogeneity compared to normal controls across different cancers. Besides, high expression of PLK1 results in shorter survival time in 15 cancer types, especially in ccRCC. PLK1 expression showed strong association with immune cell infiltration and immune checkpoint genes across cancer types. Moreover, we identified a strong association between PLK1 expression and TMB, MSI MMR, and DNA methylation. PLK1 was validated to be highly expressed in ccRCC tissues and promote ccRCC cell proliferation, migration, invasion, and cell cycle. Mechanistically, PLK1 could regulate forkhead box protein M1 and target cell cycle-associated genes to participate in cell cycle control.Conclusion: PLK1 has important prognostic value and is associated with tumor immunity across cancer types including ccRCC.Keywords: PLK1, pan-cancer analysis, ccRCC, biomarker, tumor immunity

Nitrogen removal of petrochemical wastewater through partial nitritation/anammox (PN/A) is appealing, but its feasibility and stability under toxic inhibition remain unclear. This study started a PN/A granular sludge system in a membrane bioreactor and fed it with diluted acrylic fiber wastewater. During long-term operation, the nitritation and anammox performance remained stable at a 30% volume ratio, and declined with increasing volume ratio, resulting in deteriorated nitrogen removal. Meanwhile, the short-term inhibition batch tests further showed that ammonia oxidation bacteria (AOB) in the flocs were suppressed while anammox bacteria (AnAOB) in the granules were not affected. Further analysis indicated suppression of AnAOB over the long-term operation, which was mainly caused by the disintegration of granules as demonstrated by sludge morphology. This selective inhibition is associated with variational sludge morphology, and the distribution of functional bacteria plays an important role in the feasibility and stability of PN/A treating acrylic fiber wastewater. As above, this study demonstrated the feasibility of PN/A for acrylic fiber wastewater treatment, but wastewater dilution or pre-treatment is still required for efficient nitrogen removal.

BACKGROUND AND AIM Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene glycol (PEG) for small bowel preparation before VCE. METHODS A total of 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into five groups: Group A (no PEG), Group B (1-L PEG, 12 h before VCE), Group C (2-L PEG, 12 h before VCE), Group D (1-L PEG, 4 h before VCE), and Group E (2-L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE. RESULTS Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D, and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs 32.5%, P

Shallow eutrophic lakes contribute disproportional to the emissions of CO

To explore the application value of staged urethroplasty by tubularization of the reconstructed urethral plate using the preputial island flap in the treatment of severe hypospadias.From May 2014 to February 2019, 91 children with severe hypospadias received one- or two-stage urethroplasty by tubularization of the reconstructed urethral plate with the preputial island flap. We compared the patients' age, glans diameter, length of the straightened urethral defect, and incidence rates of postoperative urethral fistula, urethral diverticulum, glans dehiscence and urethral stricture between the two groups of patients.The 56 patients in the one-stage group were aged 7－144 (21.92 ± 13.37) months old, the urethral defect 3－5 (3.565 ± 0.528) cm in length and the glans 1.0－1.4 (1.195 ± 0.083) cm in diameter, and the 35 in the two-stage group aged 7 －153 (24.78 ± 13.59) months, the urethral defect 3－5 (3.857 ± 0.696) cm in length and the glans 0.8－2.5 (1.206 ± 0.389) cm in diameter. There were no statistically significant differences in age, glans diameter and the length of urethral defect between the two groups. In the one-stage group were found 18 cases of postoperative urinary fistula, 1 case of glans dehiscence, 1 case of urethral diverticulum, and 1 case of both urethral diverticulum and glans dehiscence, all cured by repeated urinary fistula repair/urethroplasty. No urinary fistula occurred in the two-stage group postoperatively except 4 cases of glans dehiscence, of which 2 were cured by repeated repair and the other 2 refused reoperation. The success rate was significantly higher in the two-stage than in the one-stage urethroplasty group (88.57% vs 62.50%, P0.05).Two-stage urethroplasty by tubularization of the reconstructed urethral plate with the preputial island flap can significantly reduce the incidence of urethral fistula in patients with severe hypospadias, but may increase the number of operations in those who do not need staged surgery. The necessity of two-stage urethroplasty can be determined according to the development of the glans, the degree of penile curvature, and the length of urethra defect.

Acute lymphoblastic leukemia (ALL) arising in preexisting myeloproliferative neoplasms (MPN) is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Here, we report a case of patient with Philadelphia positive B lymphoblastic leukemia (Ph+ALL) who developed from MPL-mutated essential thrombocythemia (ET) 13 years after initial presentation. Molecular studies showed the discrepancy between the high percentage of lymphocyte blasts (91%) and the low MPL p.(W515L) variant allele frequency (2.59%) at diagnosis in the bone marrow, indicating that the Ph+ALL clone did not originate from the ET clone carrying the MPL p.(W515L) variant. After the treatment of a new tyrosine kinase inhibitor flumatinib and prednisolone, cytogenetic and molecular remission had been achieved rapidly and followed by the recovery of original ET manifestation. Although relapsed eventually, this is still a very rare case of simultaneous presence of two cytogenetics abnormalities and evolution of MPL p.(W515L) variant ET to Ph+ALL and may provide evidence to illustrate the clonal relationship of MPN and post-MPN ALL.

To explore the clinical and cytogenetic characteristics of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) based on morphology define.A total of 180 newly diagnosed acute myeloid leukemia (AML) patients were enrolled and retrospectively analyzed, and marrow cell morphology of 126 patients were re-evaluated. The clinical and cytogenetic characteristics, including ages, sex, WBC count, HGB level, PLT count, blasts percentage, abnormal karyotype detection rate of the patients in AML with multilineage dysplasia (AML-MRC-1), secondary AML from myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) (AML-MRC-2), and AML not otherwise specified (AML-NOS) groups were investigated.There was no significant differences between the patients in three groups in terms of sex, age and platelet count (P=0.898, P=0.365, P=0.853), but AML-MRC-2 group (73.2%) was higher than AML-MRC-1 (60.0%) and AML-NOS (56.4%) in the percentages of patients over 60 years old (P=0.228); there were statistically significant differences on WBC count, HGB level, and blasts percentage (P=0.000, P=0.022, P=0.000, AML-MRC-2AML-MRC-1AML-NOS). Abnormal karyotypes rate were 59.2% in AML-MRC patients, among which complex karyotypes and myelodysplasia-related cytogenetic abnormalities accounted for 49.3%, and 5q- was the most common (28.2%), followed by 7q-/-7 (19.1%), 17p-/-17 (14.1%), +8 (14.1%), and 20q- (12.7%). Cytogenetic abnormalities rate were compared between the patients in the three groups, the result showed that AML-MRC-2 group (73.2%) was higher than AML-MRC-1 group (40.0%) and AML-NOS group (25.4%) (P=0.000). Complex karyotypes and myelodysplasia-related abnormalities were the main abnormalities in AML-MRC-2 and AML-MRC-1 group, the percentages of complex karyotypes of the patients in the two groups showed statistically significant (41.5% vs 16.7%, P=0.026), while the percentages of other myelodysplasia-related abnormalities showed no statistically significant (17.1% vs 20.0%, P=0.753).Morphological reassessment of bone marrow cell dysplasia is crucial to the differential diagnoses between AML-MRC (defined only by morphological changes of multilineage dysplasia) and AML-NOS. And the detection rate of cytogenetic abnormalities that mainly consisted of complex karyotypes and myelodysplasia-related abnormalities was higher in AML-MRC patients.急性髓系白血病伴骨髓增生异常相关改变的临床与遗传学特征研究.探讨基于形态学定义的急性髓系白血病伴骨髓增生异常相关改变（AML-MRC）的临床和遗传学特征。.收集并回顾性分析180例新发AML患者的临床资料，并对纳入研究的126例新发AML患者骨髓涂片重新评估，研究仅形态学多系发育异常（MLD）定义的AML-MRC-1组、基于骨髓增生异常综合征（MDS）、MDS/骨髓增殖性肿瘤（MPN）病史或无MLD但存在MDS相关遗传学异常定义的AML-MRC-2组和AML非特指型（AML-NOS）组患者的年龄和性别分布、WBC数、HGB水平、PLT数、原始细胞百分比、异常核型检出率等临床和遗传学特征。.AML-MRC-1、AML-MRC-2和AML-NOS 这3组在性别和年龄分布及PLT数上差异无统计学意义（P=0.898，P=0.365, P=0.853），但60岁以上患者占比AML-MRC-2组（73.2%）高于AML-MRC-1组（60.0%）和AML-NOS组（56.4%）（P= 0.228）；3组的WBC数、HGB水平和原始细胞百分比都具有统计学差异（P=0.000, P=0.022, P=0.000），且AML-MRC-2组AML-MRC-1组AML-NOS组。AML-MRC患者异常核型总检出率为59.2%，其中复杂核型和其他MDS相关遗传学异常占49.3%，涉及5q-/-5最常见（28.2%），其次分别是：7q-/-7（19.1%）、17p-/-17（14.1%）、+8（14.1%）、20q-（12.7%）；异常核型检出率比较：AML-MRC-2组（73.2%）AML-MRC-1组（40.0%）AML-NOS组（25.4%），差异有统计学意义（P=0.000）。AML-MRC-2组和AML-MRC-1组都以复杂核型和MDS相关异常为主,两组中复杂核型占比差异有统计学意义（41.5% vs 16.7%，P=0.026）,其他MDS相关遗传学异常占比差异无统计学意义（17.1% vs 20.0%，P=0.753）。.形态学评估新发AML患者细胞发育异常是仅形态学MLD定义的AML-MRC与AML-NOS鉴别诊断的重要依据，前者遗传学异常检出率更高，且以遗传学预后高危的复杂核型和MDS相关遗传学异常为主。.

Background Underactive bladder (UAB) is a common clinical problem but related research is rarely explored. As there are currently no effective therapies, the administration of adipose stromal vascular fraction (ad-SVF) provides a new potential method to treat underactive bladder. Methods Male Sprague–Dawley rats were induced by partial bladder outlet obstruction (PBOO) for four weeks and randomly divided into three groups: rats treated with PBS (Sham group); rats administrated with ad-SVF (ad-SVF group) and rats performed with ad-SVF spheroids (ad-SVFsp group). After four weeks, urodynamic studies were performed to evaluate bladder functions and all rats were sacrificed for further studies. Results We observed that the bladder functions and symptoms of UAB were significantly improved in the ad-SVFsp group than that in the Sham group and ad-SVF group. Meanwhile, our data showed that ad-SVF spheroids could remarkably promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation in bladder tissue than that in the other two groups. Moreover, ad-SVF spheroids increased the expression levels of bFGF, HGF and VEGF-A than ad-SVF. IVIS Spectrum small-animal in vivo imaging system revealed that ad-SVF spheroids could increase the retention rate of transplanted cells in bladder tissue. Conclusions Ad-SVF spheroids improved functions and symptoms of bladder induced by PBOO, which contributes to promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation. Ad-SVF spheroids provide a potential treatment for the future patients with UAB.

Optical interference is not only a fundamental phenomenon that has enabled new theories of light to be derived but it has also been used in interferometry for the measurement of small displacements, refractive index changes and surface irregularities. In a two-beam interferometer, variations in the interference fringes are used as a diagnostic for anything that causes the optical path difference (OPD) to change; therefore, for a specified OPD, greater variation in the fringes indicates better measurement sensitivity. Here, we introduce and experimentally validate an interesting optical interference phenomenon that uses photons with a structured frequency-angular spectrum, which are generated from a spontaneous parametric down-conversion process in a nonlinear crystal. This interference phenomenon is manifested as interference fringes that vary much more rapidly with increasing OPD than the corresponding fringes for equal-inclination interference; the phenomenon is parameterised using an equivalent wavelength, which under our experimental conditions is 29.38 nm or about 1/27 of the real wavelength. This phenomenon not only enriches the knowledge with regard to optical interference but also offers promise for applications in interferometry., Comment: 16 pages, 6 figures

Background: Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) plays a vital role in providing the major part of the catalytic site of the active enzyme. Emerging evidence has revealed that P4HA1 participates in the initiation and development of several malignant tumors, nevertheless, the pan-analysis of P4HA1 remains unspecified. Methods: In this study, we carried out an in-depth analysis of the expression patterns and prognostic value of P4HA1 across the datasets of The Cancer Genome Atlas (TCGA ) and Kaplan-Meier Plotter. The genomic and epigenetic alterations, correlation with immune infiltration and DNA methylation of P4HA1 in different cancers were also analyzed across multiple databases. Moreover, we further explored the biological function and mechanism of P4HA1 in renal cell carcinoma (RCC). Results: The results characterized the different expression profile and prognostic values of P4HA1 in pan-cancer. Remarkably, P4HA1 expression was increased in kidney renal clear cell carcinoma (KIRC) and positively correlated with the OS and DFS of patients with kidney renal papillary cell carcinoma (KIRP). In addition, a positive correlation between P4HA1 expression and immune cell infiltration in KIRC was observed. We also identified a strong correlation between P4HA1 expression and immune checkpoint gene expression, microsatellite instability and tumor mutation burden in kidney chromophobe (KICH). Finally, the results of in vitro experiments verified that overexpression of P4HA1 promoted the proliferation, migration, invasion and the epithelial–mesenchymal transition (EMT) of RCC cells. Conclusion: Overall, our study suggested that P4HA1 might play a significant role in tumorigenesis and have the potential to be the target for the prognosis and therapy for several malignant tumors, especially for RCC.

Quantum nonlinear interferometers (QNIs) can measure the infrared physical quantities of a sample by detecting visible photons. A QNI with Michelson geometry based on the spontaneous parametric down-conversion in a second-order nonlinear crystal is studied systematically. A simplified theoretical model of the QNI is presented. The interference visibility, coherence length, equal-inclination interference, and equal-thickness interference for the QNI are demonstrated theoretically and experimentally. As an application example of the QNI, the refractive index and the angle between two surfaces of a BBO crystal are measured using equal-inclination interference and equal-thickness interference., 20 pages, 9 figures

This study included data from 81 consecutively enrolled patients with hematological diseases who had been treated with unrelated umbilical cord blood transplantation (UCBT) between September 2014 and April 2019. All patients received intense conditioning regimens with combined fludarabine and high-dose cyclophosphamide (FC) before undergoing UCBT. Sixty-seven patients received a single UCBT, and 14 patients received a double UCBT. Fifty patients were pretreated with the fludarabine, busulfan, and cyclophosphamide (FBC) protocol, while 31 patients were treated with FC before transplantation. Graft-versus-host disease (GVHD) was prevented with cyclosporine A and mycophenolate mofetil administration. According to low-resolution, human leukocyte antigen (HLA) donor-recipient matching at six sites, 53 patients had 5-6 matches, while 28 patients had 4 matches. Seventy-eight patients (96.3%) achieved complete engraftment in this study. Thirty-six patients developed acute GVHD (aGVHD). The cumulative incidence of grade I-II aGVHD at day 100 posthematopoietic stem cell transplantation was 29.6%, and the cumulative incidence of grade III-IV aGVHD was 14.8%. At the end of the follow-up, 12 patients died due to treatment-related complications, and 4 died of disease relapse after transplantation. The transplant-related deaths were due to transplant-related infection (8 of 81), GVHD (2 of 81), and organ toxicity (2 of 81). The probability of overall survival (OS) was 80.2%. A higher dose of cyclophosphamide combined with fludarabine conditioning in UCBT was an effective curative method for treatment of hematologic disorders and could enhance the engraftment of umbilical cord blood stem cells, promote post-transplant immune reconstitution, and improve OS.

Long non-coding RNAs (lncRNAs) contribute to colorectal cancer (CRC). However, the role of lncRNAs in CRC metabolism, especially glucose metabolism remains largely unknown. In this study, we identify a lncRNA, GLCC1, which is significantly upregulated under glucose starvation in CRC cells, supporting cell survival and proliferation by enhancing glycolysis. Mechanistically, GLCC1 stabilizes c-Myc transcriptional factor from ubiquitination by direct interaction with HSP90 chaperon and further specifies the transcriptional modification pattern on c-Myc target genes, such as LDHA, consequently reprogram glycolytic metabolism for CRC proliferation. Clinically, GLCC1 is associated with tumorigenesis, tumor size and predicts poor prognosis. Thus, GLCC1 is mechanistically, functionally, and clinically oncogenic in colorectal cancer. Targeting GLCC1 and its pathway may be meaningful for treating patients with colorectal cancer., lncRNA and cellular metabolism are frequently dysregulated in cancer. In this study, the authors discover the lncGLCC1 is increased in colorectal cancer cells under glucose starvation conditions and correlates with poor prognosis in this cancer.

Chronic myeloid leukemia (CML) and Non-Hodgkin Lymphoma (NHL) are two different origins of hematological malignancies, which rarely occur at the same time. Moreover, NHL secondary to CML is common in T cell lymphoma, while NHL of B cell origin is rare. Since 1999, only 22 cases with B cell lymphoma have been reported, of which 4 cases have diffuse large B-cell lymphoma (DLBCL). The lesions of DLBCL were in lymph node, liver, jejunum, and soft palate. To our knowledge, it has no report for the primary gastric DLBCL (PG-DLBCL) occurring in CML. Here we reported a 63-year-old man of chronic phase (CP) CML associated with PG-DLBCL. The patient was diagnosed with CML nearly eight years ago and was treated with imatinib and nilotinib successively. However, gastroscopy found malignant lesions in the patient's stomach in March 2018, and the masses were diagnosed as PG-DLBCL. Subsequently, with the treatment of the RCOP + lenalidomide regimen chemotherapy for 3 cycles, the patient achieved nearly complete remission (CR).

The recombination mediated by recombination activating gene (RAG) is not only the dominant mutational process but also the predominant driver of oncogenic genomic rearrangement in acute lymphoblastic leukemia (ALL). It is further responsible for leukemic clonal evolution. In this study, significant RAG1 increase is observed in the subsets of B-ALL patients, and high expression of RAG1 is observed to be correlated with high proliferation markers. IKZF1-encoded protein, IKAROS, directly binds to the RAG1 promoter and regulates RAG1 expression in leukemic cells. CK2 inhibitor by increasing IKAROS activity significantly suppresses RAG1 expression in ALL in an IKAROS-dependent manner. Patients with IKZF1 deletion have significantly higher expression of RAG1 compared to that without IKZF1 deletion. CK2 inhibitor treatment also results in an increase in IKZF1 binding to the RAG1 promoter and suppression of RAG1 expression in primary ALL cells. Taken together, these results demonstrate that RAG1 high expression is associated with high proliferation markers in B-ALL. Our data for the first time proved that RAG1 expression is directly suppressed by IKAROS. Our results also reveal drive oncogenesis of B-ALL is driven by high expression of RAG1 with IKAROS dysfunction together, which have significance in an integrated prognostic model for adult ALL.

Ikaros encodes a transcription factor that functions as a tumor suppressor in T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms through which Ikaros regulates gene expression and cellular proliferation in T-ALL are unknown. Re-introduction of Ikaros into Ikaros-null T-ALL cells resulted in cessation of cellular proliferation and induction of T-cell differentiation. We performed dynamic, global, epigenomic, and gene expression analyses to determine the mechanisms of Ikaros tumor suppressor activity. Our results identified novel Ikaros functions in the epigenetic regulation of gene expression: Ikaros directly regulates de novo formation and depletion of enhancers, de novo formation of active enhancers and activation of poised enhancers; Ikaros directly induces the formation of super-enhancers; and Ikaros demonstrates pioneering activity by directly regulating chromatin accessibility. Dynamic analyses demonstrate the long-lasting effects of Ikaros DNA binding on enhancer activation, de novo formation of enhancers and super-enhancers, and chromatin accessibility. Our results establish that Ikaros’ tumor suppressor function occurs via global regulation of the enhancer and super-enhancer landscape and through pioneering activity. Expression analysis identified a large number of novel signaling pathways that are directly regulated by Ikaros and Ikaros-induced enhancers, and that are responsible for the cessation of proliferation and induction of T-cell differentiation in T-ALL cells.

Purpose: To investigate the overall efficacy and toxicity of cladribine and cladribine-based chemotherapy in the treatment of patients with refractory acute myeloid leukemia (AML) based on meta-analysis. Methods: PubMed, EMBASE database, and the Cochrane Library were searched for relevant studies. Eligible studies were clinical trials of refractory AML assigned to cladribine with data on efficacy including complete remission (CR) rate, overall response rate (ORR) and overall survival. Toxicity was evaluated based on the early death rate and the incidence of grade 3 and 4 adverse events (AEs). Results: A total of 10 clinical trials including 422 refractory AML patients were analyzed. The overall CR rate was 42.2% (95% CI: 31.0-54.3%). And the ORR of seven trials including 235 patients was 49.7% (95% CI: 33.5-66.0%). The overall early death rate of 260 patients enrolled in five trials was 6.8% (95% CI: 4.3-10.6%). Thrombocytopenia, anemia, neutropenia, and infection were the most common grade 3 and 4 AEs. Conclusion: Cladribine is effective for refractory AML, and its efficacy can be increased with the combination of cladribine, cytarabine, and granulocyte-colony stimulating factor regimen.

In this paper some new Z-eigenvalue localization sets for general tensors are established, which are proved to be tighter than those newly derived by Wang et al. [Discrete Contin. Dyn. Syst. Ser. B, 22 (2017), 187–198]. Also, some relationships between the Z-eigenvalue inclusion sets presented by Wang et al. and the new Z-eigenvalue localization sets for tensors are given. Besides, we discuss the effects of orthonormal transformations for the proposed sets. As applications of the proposed sets, some improved upper bounds for the Z-spectral radius of weakly symmetric nonnegative tensors are given. Numerical examples are also given to verify the advantages of our proposed results over some known ones.

Background Tripartite motif 47 (TRIM47), a member of the TRIM family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). We found that levels of TRIM47 mRNA and protein were increased significantly in colorectal tumors compared with nontumor tissues and the increased levels were associated with advanced tumor stage and poor outcome. Methods We used quantitative polymerase chain reaction and western blot to measure levels of TRIM47 mRNA and protein in human colorectal cancer and paired normal tissues. TRIM47 was knocked down and overexpressed in colorectal cancer cells, and the effects on cell proliferation, migration and growth of xenograft tumors in nude mice were assessed. The signaling pathways were examined by western blot and immunoprecipitation assays. Results TRIM47 promoted CRC proliferation and metastasis in vitro and in vivo as an oncogene. Mechanistically, TRIM47 interacted physically with SMAD4, increasing its ubiquitination and degradation. Loss of SMAD4 leaded to up-regulation of CCL15 expression and caused growth and invasion in human CRC cells through the CCL15-CCR1 signaling. Moreover, TRIM47 overexpression played a role in CRC chemoresistance in response to 5-FU therapy. Conclusions Our study demonstrated a functional role of the TRIM47-SMAD4-CCL15 axis in CRC progression and suggested a potential target for CRC therapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1143-x) contains supplementary material, which is available to authorized users.

In this paper, by adopting the preconditioned technique for the accelerated generalized successive overrelaxation method (AGSOR) proposed by Edalatpour et al. (2015), we establish the preconditioned AGSOR (PAGSOR) iteration method for solving a class of complex symmetric linear systems. The convergence conditions, optimal iteration parameters and corresponding optimal convergence factor of the PAGSOR iteration method are determined. Besides, we prove that the spectral radius of the PAGSOR iteration method is smaller than that of the AGSOR one under proper restrictions, and its optimal convergence factor is smaller than that of the preconditioned symmetric block triangular splitting (PSBTS) one put forward by Zhang et al. (2018) recently. The spectral properties of the preconditioned PAGSOR matrix are also proposed. Numerical experiments illustrate the correctness of the theories and the effectiveness of the proposed iteration method and the preconditioner for the generalized minimal residual (GMRES) method.

Background: Gastric cancer (GC) is one of the most lethal cancers worldwide with a high risk for recurrence and metastasis. Therefore, further understanding of the metastatic mechanism and the development of treatment strategies are required. Although increasing evidence suggests that SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily E, Member 1 (SMARCE1) promotes cancer metastasis, its role in GC remains unclear. Materials and methods: GC samples (n=122) were used to investigate the association between SMARCE1 expression, patient clinicopathological features, and prognosis. The expression of SMARCE1 in GC tissues was measured using real-time polymerase chain reaction, western blotting, and immunohistochemistry. MGC-803 and AGS cells were transfected with lentivirus to upregulate or downregulate SMARCE1 expression. The roles of SMARCE1 in GC cell proliferation, migration, and invasion were determined using Cell Counting Kit-8 assay, colony formation assay, wound healing, transwell migration, and invasion assay. Nude mice models were established to observe tumorigenesis. The specific mitogen-activated protein kinase (MAPK) inhibitor U0126 was utilized to verify the involved pathway. Results: SMARCE1 was highly expressed in GC tissues and cell lines. High expression of SMARCE1 was correlated with the malignant clinicopathological characteristics of GC patients, including tumor size, depth of invasion, degree of differentiation, lymph node involvement, and TNM stage (all P

Quizartinib is an effective therapy for patients with FLT3-ITD acute myeloid leukemia (AML) by continuing to inhibit the activity of FLT3 gene, leading to apoptosis of tumor cells. Multiple clinical trials have proved that it is effective in relapsed or refractory AML with an FLT3-ITD mutation. In this review, we focus on the characteristics of FLT3/ITD mutations, the mechanism and pharmacokinetics of quizartinib, and the mechanisms of resistance to quizartinib. We also summarize clinical experiences and adverse effects with quizartinib and recommend crucial approaches of quizartinib in the therapy of patients with newly diagnosed AML and patients with relapsed/refractory AML, particularly those with FLT3-ITD mutation. Quizartinib presents its advantages as a very promising agent in the treatment of AML, especially in patients with FLT3-ITD mutations. FLT3/ITD mutation can lead to constitutive autophosphorylation of FLT3 and activation of its downstream effectors including RAS/RAF/MEK, MAPK/ERK, PI3K/AKT/mTOR and JAK/STAT5 signal pathways, while Quizartinib can inhibit these downstream pathways through specific FLT3 inhibition. Quizartinib has received US Food and Drug Administration breakthrough therapy designation in patients with relapsed/refractory FLT3-ITD AML based on clinical trials. A larger sample of clinical trials are needed to verify its safety and efficacy, and the efficacy of quizartinib combined with chemotherapy or allogeneic hematopoietic cell transplantation should also be estimated in clinical trials. Meanwhile, for the side effects of quizartinib, further studies are needed to find a way to reduce its toxicity.

For solving ill-posed inverse problems, we establish a modified version of special Hermitian and skew-Hermitian splitting (SHSS) iteration method, called the modified SHSS (MSHSS) method in this pa...

Based on trajectory planning with maximum velocity and acceleration constraints, a novel high-quality trajectory planning method was proposed for heterogeneous individuals in crowd simulation. The proposed method ensured that the individual’s path was smooth and its velocity was continuous. Based on the physiological constraints of humans with maximum velocity and acceleration, time-optimal trajectory and feasible region were derived by solving kinodynamic planning problem. Subsequently, a high-quality trajectory planning algorithm was designed to compute the trajectory with appropriate variation of velocity. The simulation results demonstrate that the proposed trajectory planning method has more authenticities and can generate high-quality trajectories for virtual humans in crowd simulation.

BACKGROUND This case-control study compared the short-term clinical efficacy of natural orifice specimen extraction surgery (NOSES) using a prolapsing technique and the conventional laparoscopic-assisted approach for low rectal cancer. AIM To further explore the application value of the transanal placement of the anvil and to evaluate the short-term efficacy of NOSES for resecting specimens of low rectal cancer, as well as to provide a theoretical basis for its extensive clinical application. METHODS From June 2015 to June 2018, 108 consecutive laparoscopic-assisted low rectal cancer resections were performed at our center. Among them, 26 specimens were resected transanally using a prolapsing technique (NOSES), and 82 specimens were resected through a conventional abdominal wall small incision (LAP). A propensity score matching method was used to select 26 pairs of matched patients, and their perioperative data were analyzed. RESULTS The baseline data were comparable between the two matched groups. All 52 patients underwent the surgery successfully. The operative time, blood loss, number of harvested lymph nodes, postoperative complication rate, circumferential margin involvement, postoperative follow-up data, and postoperative anal function were not statistically significant. The NOSES group had shorter time to gastrointestinal function recovery (2.6 ± 1.0 d vs 3.4 ± 0.9 d, P = 0.006), shorter postoperative hospital stay (7.1 ± 1.7 d vs 8.3 ± 1.1 d, P = 0.003), lower pain score (day 1: 2.7 ± 1.8 vs 4.6 ± 1.9, day 3: 2.0 ± 1.1 vs 4.1 ± 1.2, day 5: 1.7 ± 0.9 vs 3.3 ± 1.0, P < 0.001), a lower rate of additional analgesic use (11.5% vs 61.5%, P = 0.001), and a higher satisfaction rate in terms of the aesthetic appearance of the abdominal wall after surgery (100% vs 23.1%, P < 0.001). CONCLUSION NOSES for low rectal cancer can achieve satisfactory short-term efficacy and has advantages in reducing postoperative pain, shortening the length of postoperative hospital stay, and improving patients’ satisfaction in terms of a more aesthetic appearance of the abdominal wall.