Publications by authors named "Zhiyu Liu"

133 Publications

Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis.

Front Oncol 2021 1;11:731318. Epub 2021 Oct 1.

Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Background: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.

Methods: We first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.

Results: Firstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan-Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).

Conclusions: Preoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.
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http://dx.doi.org/10.3389/fonc.2021.731318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519510PMC
October 2021

First trimester exposure to ambient gaseous air pollutants and risk of orofacial clefts: a case-control study in Changsha, China.

BMC Oral Health 2021 Oct 15;21(1):530. Epub 2021 Oct 15.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Xiangya Road, Kaifu District, Changsha, 410078, China.

Background: A growing body of studies have investigated the association between air pollution exposure during early pregnancy and the risk of orofacial clefts, but these studies put more emphasis on particulate matter and reported inconsistent results, while research on the independent effects of gaseous air pollutants on orofacial clefts has been quite inadequate, especially in China.

Methods: A case-control study was conducted in Changsha, China from 2015 to 2018. A total of 446 cases and 4460 controls were included in the study. Daily concentrations of CO, NO, SO, O, PM and PM during the first trimester of pregnancy were assigned to each subject using the nearest monitoring station method. Multivariate logistic regression models were applied to evaluate the associations of monthly average exposure to gaseous air pollutants with orofacial clefts and its subtypes before and after adjusting for particulate matter. Variance inflation factors (VIFs) were used to determine if the effects of gaseous air pollutants could be independent of particulate matter.

Results: Increase in CO, NO and SO significantly increased the risk of cleft lip with or without cleft palate (CL/P) in all months during the first trimester of pregnancy, with aORs ranging from 1.39 to 1.48, from 1.35 to 1.61 and from 1.22 to 1.35, respectively. The risk of cleft palate only (CPO) increased with increasing NO exposure levels in the first trimester of pregnancy, with aORs ranging from 1.60 to 1.66. These effects sustained and even exacerbated after adjusting for particulate matter. No significant effect of O was observed.

Conclusions: Our study suggested that maternal exposure to CO, NO, and SO during the first trimester of pregnancy might contribute to the development of orofacial clefts, and the associations were potentially independent of particulate matter.
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http://dx.doi.org/10.1186/s12903-021-01876-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518237PMC
October 2021

Mussel-Inspired Ag NPs Immobilized on Melamine Sponge for Reduction of 4-Nitrophenol, Antibacterial Applications and Its Superhydrophobic Derivative for Oil-Water Separation.

ACS Appl Mater Interfaces 2021 Oct 12;13(42):50539-50551. Epub 2021 Oct 12.

School of Food and Biological Engineering, Xuzhou University of Technology, Xuzhou, 221018, People's Republic of China.

A functional material integrated with a variety of functions is highly desired in wastewater treatment. In this research, a mussel-inspired method of immobilizing silver nanoparticles on the skeleton of a melamine sponge is proposed and applied for water remediation. Ag NPs were reduced in situ and grown on a polydopamine-modified melamine sponge. The catalytic reduction of 4-nitrophenol (4-NP) in the presence of the obtained MS-PDA-Ag was evaluated, and the results demonstrated that the MS-PDA-Ag presented high catalytic reduction activity. In addition, the monolithic MS-PDA-Ag presents excellent reusability with no remarkable decrease in catalytic efficiency after multiple reuses. Owing to the immobilized Ag NPs, the MS-PDA-Ag can also effectively inhibit the growth of bacteria against both gram-positive and gram-negative species, making it possible for bacteria elimination in polluted water. To further explore the possibility of utilizing the MS-PDA-Ag for versatile applications, a superhydrophobic derivative (S-MS-PDA-Ag) was prepared by coating a low-surface-energy substance (octadecanethiol) on the surface of MS-PDA-Ag. The obtained S-MS-PDA-Ag presents the capacities of oil/organics adsorption and water repellence, which can separate the insoluble oil/organics from water. The melamine sponge immobilized with Ag NPs demonstrates prominent catalytic reduction of 4-NP, antibacterial activity and the superhydrophobic derivative presents the capacity of insoluble oil/organics separation from oil-water mixtures, exhibiting high potential in the remediation of polluted water.
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http://dx.doi.org/10.1021/acsami.1c14544DOI Listing
October 2021

Integrity of cfDNA in maternal plasma extracellular vesicles as a potential biomarker for NIPT.

Int J Gynaecol Obstet 2021 Oct 9. Epub 2021 Oct 9.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.

Objective: Large proportion of cfDNA in plasma are localized in extracellular vesicles (EVs), which are secreted from placental cells. This study was conducted to reveal the integrity pattern of cfDNA in maternal plasma EVs (evcfDI) across gestation, and explore if evcfDI could be a potential biomarker in screening aneuploid fetus in NIPT.

Methods: A total of 180 maternal plasma samples were collected during NIPT. EvcfDNA and evcffDNA were measured by qPCR of LINE1 and SRY gene amplicons with different sizes. EvcfDI was calculated as the ratio of long to short fragments.

Results: EvcfDI is not affected by gestational age; while evcffDI has a mild decreasing trend with increasing gestational age (p=0.048). EvcfDI is significantly and negatively correlated with maternal BMI (≤18.5, 18.5-25, and ≥25 kg/m ) (p<0.01) and age (<35 and ≥35) (p<0.01). Mean evcfDI decreases from 2.113 in euploid controls to 0.681 in those with aneuploid fetus in NIPT (p=0.003).

Conclusion: Maternal clinical characteristics as BMI and agecould be an innovative biomarker to calibrate evcfDI. EvcfDI was shown as a potential indicator of aneuploid fetus. EvcfDI analysis based on qPCR could serve as a novel, rapid, and low-cost NIPT strategy, which might facilitate test in earlier gestation.
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http://dx.doi.org/10.1002/ijgo.13976DOI Listing
October 2021

Effects of pre-pregnancy body mass index on pregnancy and perinatal outcomes in women based on a retrospective cohort.

Sci Rep 2021 Oct 6;11(1):19863. Epub 2021 Oct 6.

NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, 58 Xiangchun Road, Changsha, 410078, Hunan, China.

To investigate the prevalence of underweight, overweight and obesity as defined by pre-pregnancy body mass index (BMI) and the relationship between pre-pregnancy BMI and pregnancy and perinatal outcomes in women based on a retrospective cohort. Women registered via the Free Pre-pregnancy Health Check (FPHC) program from 2017 to 2019 in Hunan Province, China, were included to the study cohort. The data regarding maternal characteristics, pregnancy outcomes, and infant characteristics were retrieved from the surveillance system of the FPHC program. Logistic regressions were performed to calculate odds ratios (ORs) and adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs) to assess the associations between pre-pregnancy BMIs and the outcomes. Among a total of 398,368 women, 54,238 (13.62%) were underweight (BMI < 18.5 kg/m), 51,251 (12.87%) were overweight (24.0 kg/m ≤ BMI < 28.0 kg/m), and 10,399 (2.61%) were obese (BMI ≥ 28.0 kg/m). Underweight occurred more commonly in the 20-24 years old (17.98%), Han Chinese (13.89), college-educated (16.09%), rural (13.74%), and teacher/public servant/office clerk (16.09%) groups. Obesity occurred more often in the older than 35-year-old (4.48%), minority (3.64%), primary school or below (4.98%), urban (3.06%), and housewife (3.14%) groups (P < 0.001). Compared with the normal BMI group, underweight was associated with increased risk of low birth weight (LBW) (AOR = 1.25) and small-for-gestational age (SGA) (AOR = 1.11), but protected against gestational hypertensive disorder (GHD) (AOR = 0.85), gestational diabetes mellitus (GDM) (AOR = 0.69), macrosomia (AOR = 0.67), post-term pregnancy (AOR = 0.76), and cesarean-section (AOR = 0.81). Overweight and obesity were associated with increased risk of GHD (AOR = 1.28, 2.47), GDM (AOR = 1.63, 3.02), preterm birth (AOR = 1.18, 1.47), macrosomia (AOR = 1.51, 2.11), large-for-gestational age (LGA) (AOR = 1.19, 1.35), post-term pregnancy (AOR = 1.39, 1.66), and cesarean- section (AOR = 1.60, 2.05). Pre-pregnancy underweight is relatively common in Hunan Province, China. Pre-pregnancy underweight to some extent is associated with better maternal outcomes, but it has certain adverse effects on neonatal outcomes. Pre-pregnancy overweight, especially obesity, has a substantial adverse effect on pregnancy and perinatal outcomes.
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http://dx.doi.org/10.1038/s41598-021-98892-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494740PMC
October 2021

Accidental death during pregnancy and puerperium from 2009 to 2019 in Hunan, China: a cross-sectional study.

BMJ Open 2021 09 30;11(9):e047660. Epub 2021 Sep 30.

Information Management Section, Hunan Province, Changsha, Hunan, China

Objective: Few studies have analysed accidental maternal deaths. This study analysed the basic situation and classification of maternal accidental deaths and compared the differences between urban and rural areas.

Design: A cross-sectional study on accidental deaths during pregnancy and puerperium from 2009 to 2019 in Hunan Province.

Setting: Hunan Province, with a population of 74 million, has an area of 210 000 km and 123 counties/districts.

Participants: A collection of 239 cases of accidental death during pregnancy and puerperium in Hunan Province from 2009 to 2019, including 181 cases of rural pregnancy and puerperium and 58 cases of urban pregnancy and puerperium.

Main Outcome Measure: Classification of accidental mortality of pregnant women.

Results: A total of 239 accidental deaths occurred in Hunan Province, with an accidental mortality rate of 2.8 per 100 000 live births. The accidental mortality rate in rural areas (3.2 per 100 000 live births) was higher than in urban areas (2.0 per 100 000 live births). The proportion of accidental deaths among pregnancy-related deaths showed an upward trend. The main types of accidental deaths were suicide (1.0 per 100 000 live births), traffic accidents (0.8 per 100 000 live births), accidental poisoning/overdose and assault/homicide (0.2 per 100 000 live births), and other accidents (0.6 per 100 000 live births). Maternal accidental deaths were mainly concentrated in low-income families, in rural areas and in those with low level of education. 74.5% of accidental deaths occurred before childbirth. 49.2% of pregnant women gave birth by caesarean section.

Conclusion: In response to the different causes of accidental maternal death, public health programmes and policy interventions should pay special attention to maternal suicide and traffic injuries.
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http://dx.doi.org/10.1136/bmjopen-2020-047660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487173PMC
September 2021

Chemically driven energetic molecular ferroelectrics.

Nat Commun 2021 Sep 29;12(1):5696. Epub 2021 Sep 29.

Department of Mechanical and Aerospace Engineering, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA.

Chemically driven thermal wave triggers high energy release rate in covalently-bonded molecular energetic materials. Molecular ferroelectrics bridge thermal wave and electrical energy by pyroelectric associated with heating frequency, thermal mass and heat transfer. Herein we design energetic molecular ferroelectrics consisting of imidazolium cations (energetic ion) and perchlorate anions (oxidizer), and describe its thermal wave energy conversion with a specific power of 1.8 kW kg. Such a molecular ferroelectric crystal shows an estimated detonation velocity of 7.20 ± 0.27 km s comparable to trinitrotoluene and hexanitrostilbene. A polarization-dependent heat transfer and specific power suggests the role of electron-phonon interaction in tuning energy density of energetic molecular ferroelectrics. These findings represent a class of molecular ferroelectric energetic compounds for emerging energy applications demanding high power density.
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http://dx.doi.org/10.1038/s41467-021-26007-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481480PMC
September 2021

Textbook Outcome as a measure of surgical quality assessment and prognosis in gastric neuroendocrine carcinoma: A large multicenter sample analysis.

Chin J Cancer Res 2021 Aug;33(4):433-446

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China.

Objective: Quality assurance is crucial for oncological surgical treatment assessment. For rare diseases, single-quality indicators are not enough. We aim to develop a comprehensive and reproducible measurement, called the "Textbook Outcome" (TO), to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma (G-NEC) patients.

Methods: Data from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed. TO included receiving a curative resection, ≥15 lymph nodes examined, no severe postoperative complications, hospital stay ≤21 d, and no hospital readmission ≤30 d after discharge. Hospital variation in TO was analyzed using a case mix-adjusted funnel plot. Prognostic factors of survival and risk factors for non-Textbook Outcome (non-TO) were analyzed using Cox and logistic models, respectively.

Results: TO was achieved in 56.6% of 860 G-NEC patients. TO patients had better overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) than non-TO patients (P<0.05). Moreover, TO patients accounted for 60.3% of patients without recurrence. Multivariate Cox analysis revealed non-TO as an independent risk factor for OS, DFS, and RFS of G-NEC patients (P<0.05). Increasing TO rates were associated with improved OS for G-NEC patients, but not hospital volume. Multivariate logistic regression revealed that non-lower tumors, open surgery, and >200 mL blood loss were independent risk factors for non-TO patients (P<0.05).

Conclusions: TO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients. Factors predicting non-TO are identified, which may help guide strategies to optimize G-NEC outcomes.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.04.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435827PMC
August 2021

Heat Treatment Induced Specified Aggregation Morphology of Metoprolol Tartrate in Poly(ε-caprolactone) Matrix and the Drug Release Variation.

Polymers (Basel) 2021 Sep 13;13(18). Epub 2021 Sep 13.

The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Sichuan Provincial Engineering Laboratory of Plastic/Rubber Complex Processing Technology, Sichuan University, Chengdu 610065, China.

Hot-melt blending has been widely used in the pharmaceutical industry to produce drug delivery systems, however, realizing the controlled drug release behavior of a hot-melt blended medicament it is still a tough challenge. In this study, we developed a simple and effective heat treatment method to adjust the drug release behavior, without the addition of any release modifiers. Thin metoprolol tartrate (MPT)/poly(ε-caprolactone) (PCL) tablets were prepared through hot-melt processing, and different morphologies of MPT were obtained by altering processing temperatures and the following heat treatment. MPT particles with different particle sizes were obtained under different processing temperatures, and fibrous crystals of MPT were fabricated during the following heat treatment. Different morphological structures of MPT adjusted the drug diffusion channel when immersed in phosphate-buffered saline (PBS), and various drug release behaviors were approached. After being immersed for 24 h, 7% of the MPT was released from the blend processed at 130 °C, while more than 95% of the MPT were released after the following heat treatment of the same sample. Thus, flexible drug release behaviors were achieved using this simple and effective processing manufacture, which is demonstrated to be of profound importance for biomedical applications.
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http://dx.doi.org/10.3390/polym13183076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471319PMC
September 2021

A Facile and Scalable Method of Fabrication of Large-Area Ultrathin Graphene Oxide Nanofiltration Membrane.

ACS Nano 2021 Sep 3;15(9):15294-15305. Epub 2021 Sep 3.

Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong SAR 999077, China.

With their ultrafast water transport and excellent molecule sieving properties, graphene oxide (GO)-based membranes show great potential in the membrane filtration field for water purification and molecular separation. However, the inability of uniform GO membranes to be produced on an industrial scale and their nonenvironmentally friendly reduction treatment are the bottleneck preventing their industrial applications. Herein, we report a scalable ultrathin uniform GO membrane fabrication technique. Ultrathin GO membranes with a large area of 30 × 80 cm and a thickness of a few nanometers were uniformly and facilely fabricated using a continuous process combining Mayer rod-coating and a short-time, high-power UV reduction. The interlayer spacing of the GO membrane could be effectively reduced and regulated to improve the salt rejection rate. The fabricated membrane showed superior water permeability of over 60.0 kg m h and a high separation efficiency of over 96.0% for a sodium sulfate (NaSO) solution. It also exhibited excellent mechanical stability under various harsh crossflow conditions. More importantly, the fabrication method developed here can be scaled up using a roll-to-roll industrial production process, which successfully solves the problem currently faced by GO membrane researchers and makes the industrial usage of GO membrane a reality.
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http://dx.doi.org/10.1021/acsnano.1c06155DOI Listing
September 2021

Modification of the effects of nitrogen dioxide and sulfur dioxide on congenital limb defects by meteorological conditions.

Hum Reprod 2021 Oct;36(11):2962-2974

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.

Study Question: Can meteorological conditions modify the associations between NO2 and SO2 exposure and congenital limb defects (CLDs) during the first trimester of pregnancy?

Summary Answer: Increases in NO2 and SO2 exposure were consistently associated with higher risks of CLDs during the first trimester of pregnancy; both low- and high-temperature exposure and high air humidity act synergistically with the two air pollutants on CLDs.

What Is Known Already: Animal studies have indicated air pollutants are associated with CLDs, but corresponding epidemiological studies are limited with equivocal conclusions. Meteorological conditions are closely connected to the generation, diffusion, distribution and even chemical toxicity of air pollutants.

Study Design, Size, Duration: This case-control study included 972 cases of CLDs and 9720 controls in Changsha, China during 2015-2018.

Participants/materials, Setting, Methods: Cases from the hospital based monitoring system for birth defects (including polydactyly, syndactyly, limb shortening, and clubfoot) and healthy controls from the electronic medical records system were studied. Complete data on daily average NO2 and SO2 concentrations and meteorological variables were obtained from local monitoring stations to estimate monthly individual exposures during the first trimester of pregnancy, using the nearest monitoring station approach for NO2 and SO2 concentrations, and the city-wide average approach for temperature and relative humidity, respectively. The 25th and 75th percentiles of daily mean temperature, as well as the 50th percentile of daily mean relative humidity during the study period were used to classify high- and low-temperature exposure, and high humidity exposure based on existing evidence and local climate characteristics. Multivariate logistic regression models were used to estimate the independent effects per 10 μg/m3 increase in NO2 and SO2 on CLDs, and the attribute proportions of interaction (API) were used to quantify the additive joint effects of air pollutants with meteorological conditions after including a cross product interaction term in the regression models.

Main Results And The Role Of Chance: NO2 and SO2 exposures during the first trimester of pregnancy were consistently and positively associated with overall CLDs and subtypes, with adjusted odd ratios (aORs) ranging from 1.13 to 1.27 for NO2, and from 1.37 to 2.49 for SO2. The effect estimates were generally observed to be the strongest in the first month and then attenuated in the second and third months of pregnancy. Synergistic effects of both low and high temperature in combination with NO2 (with APIs ranging from 0.07 to 0.38) and SO2 (with APIs ranging from 0.18 to 0.51) appeared in the first trimester of pregnancy. Several significant modifying effects by high humidity were also observed, especially for SO2 (with APIs ranging from 0.13 to 0.38). Neither NO2 nor SO2 showed an interactive effect with season of conception.

Limitations, Reasons For Caution: The methods used to estimate individual exposure levels of air pollutants and meteorological factors may lead to the misclassification bias because of the lack of information on maternal activity patterns and residential mobility during pregnancy. Moreover, we were unable to consider several potentially confounding factors, including socioeconomic status, maternal nutrient levels, alcohol use and smoking during early pregnancy due to unavailable data, although previous studies have suggested limited change to the results after when including these factors in the analysis.

Wider Implications Of The Findings: The findings are helpful for understanding the combined effects of air pollution and meteorological conditions on birth defects. Environmental policies and practices should be formulated and implemented to decrease air pollutant emissions and improve meteorological conditions to reduce their harmful effects on pregnancy. Additionally, pregnant women should be suggested to reduce outdoor time when the air quality is poor, especially when ambient temperature is higher or lower than what is comfortable, or when it is excessively humid.

Study Funding/competing Interest(s): The study is funded by Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (2019SK1012), Major Research and Development Projects in Hunan Province (2018SK2060) and Scientific and Technological Department Projects in Hunan Province (2017SK50802). There are no competing interests.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deab187DOI Listing
October 2021

Targeting c-MET to Enhance the Efficacy of Olaparib in Prostate Cancer.

Onco Targets Ther 2021 4;14:4383-4389. Epub 2021 Aug 4.

Department of Urinary Surgery, Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.

Purpose: Prostate cancer is the second leading cause of cancer death in men worldwide. Olaparib is clinically approved for the treatment prostate cancer, but cytotoxicity and off-target effects including DNA damage limit its clinical applications. In the current study, new strategies to improve the therapeutic efficacy of olaparib for the treatment of prostate cancer were investigated.

Methods: Two prostate cancer cell lines were exposed to the c-MET inhibitor PHA665752 and/or the PARP inhibitor olaparib. Cell counting kit-8, colony formation assays, and transwell assays were conducted to evaluate the cytotoxicity of olaparib alone or in combination with PHA665752 in prostate cancer cell lines. Western blotting, immunofluorescence staining, and the comet assay were used to assess the effects of PHA665752 on olaparib-induced DNA damage.

Results: Combined inhibition of c-MET and PARP resulted in effective and synergistic blocking of the growth of prostate cancer cell lines. Invasion and migration were significantly suppressed when the agents were combined. Mechanistically, dual blocking of PARP and c-MET in prostate cancer cell lines was associated with an impaired DNA damage response. Interestingly, immunofluorescence staining analysis of RAD51 protein indicated that the c-MET inhibitor PHA665752 significantly impaired homologous repair via downregulated translocation of RAD51 into the nucleus in prostate cancer cells.

Conclusion: The combination of the c-MET inhibitor PHA665752 and the PARP inhibitor olaparib may be a promising therapeutic strategy in patients with prostate cancer.
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http://dx.doi.org/10.2147/OTT.S291267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349550PMC
August 2021

Magnetic Resonance Imaging (MRI)-Targeted Biopsy in Patients with Prostate-Specific Antigen (PSA) Levels <20 ng/mL: A Single-Center Study in Northeastern China.

Med Sci Monit 2021 Aug 8;27:e930234. Epub 2021 Aug 8.

Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China (mainland).

BACKGROUND We investigated the feasibility of applying magnetic resonance imaging (MRI)-targeted biopsy (TB) in patients with prostate-specific antigen (PSA) levels <20 ng/mL. MATERIAL AND METHODS We retrospectively analyzed 218 patients with PSA levels <20 ng/mL and suspicious lesions according to the Prostate Imaging Recording and Data System version 2.0 (PI-RADS v2). All 218 men underwent transperineal MRI-TB, followed by template-guided 12-core systematic biopsy (SB). Of the 218 patients undergoing TB, 100 received MRI-ultrasound-assisted software fusion biopsy (FB) and 118 received cognitive biopsy (CB). Clinically significant prostate cancer (csPCa) was defined as a Gleason score ≥3+4. RESULTS The overall TB positive rate was similar to that of SB (P=0.156), but with a higher diagnostic rate for csPCa (P=0.034). SB misdiagnosed csPCa in 11.47% of cases; TB misdiagnosed csPCa in 5.50% of cases. SB+TB detected more tumors with a Gleason score of 7 than did SB alone (43 vs 22). Detection rates of csPCa were similar for CB and FB (P=0.217). In total, 47 men had 2 MRI-determined suspicious areas. Of 265 suspicious areas, 143 (53.96%) had a PI-RADS v2 score of 3; 92 (34.71%) had a score of 4; and 30 (11.32%) had a score of 5. The positive detection rates for csPCa in patients with PI-RADS v2 scores of 3, 4, and 5, were 11.19%, 48.91%, and 80.00%, respectively. CONCLUSIONS TB increased the positive biopsy detection rate but missed some cases of csPCa. TB combined with SB may be the most suitable biopsy for patients with PSA <20 ng/mL.
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http://dx.doi.org/10.12659/MSM.930234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359686PMC
August 2021

Bivalirudin versus unfractionated heparin during percutaneous coronary intervention in high-bleeding-risk patients with acute coronary syndrome in contemporary practice.

Biomed Pharmacother 2020 Oct 17;130:110758. Epub 2020 Sep 17.

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address:

Background: Bivalirudin, as compared with unfractionated heparin (UFH), has been shown to reduce bleeding complications and supply a better safety profile among low/medium-bleeding-risk patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) in some previous studies. Whether this advantage persists in patients at high risk of bleeding according to contemporary practice characterized by frequent use of radial-artery access and novel P2Y inhibitors, and low use of glycoprotein IIb/IIIa inhibitors (GPIs) is unclear.

Aim Of The Study: This study aimed to assess the efficacy and safety of bivalirudin compared with UFH in high bleeding risk patients with ACS undergoing PCI in current practice.

Materials And Methods: All consecutive high-bleeding-risk patients who underwent PCI for ACS at the First Affiliated Hospital of Zhengzhou University from January to September 2019 were retrospectively analyzed. The 30-day primary outcome was a composite of major bleeding, myocardial infarction, all-cause death, or stroke (net adverse clinical events [NACEs]), and the secondary outcomes at 30 days included a composite of myocardial infarction, stoke, or all-cause death (major adverse cardiovascular events [MACEs]), each component of the primary outcome, target vessel revascularization (TVR) and stent thrombosis (ST). Besides, we assessed angina-related health status at 30 days, the length of hospital stay, and hospitalization costs. A logistic regression model was used to adjust for baseline differences. Consistency of the treatment effect of bivalirudin for NACEs and MACEs compared with UFH was evaluated in 15 prespecified subgroups.

Results: From January to September 2019, 823 patients (361 treated with bivalirudin and 462 treated with UFH) were enrolled in the study. GPIs, novel P2Y inhibitors, and radial approach was used in 5.6 %, 66.1 %, and 89.7 % of the patients, respectively. After adjusting for baseline differences, bivalirudin was associated with significant reduction in NACEs, MACEs, major bleeding, and myocardial infarction at 30 days compared with UFH. The individual endpoints of death, stroke, ST and TVR did not differ significantly between the 2 groups after adjusting for covariates. Furthermore, bivalirudin consistently reduced the rates of NACEs and MACEs in the 15 prespecified subgroups compared with UFH. These benefits of bivalirudin can translate into improved angina-related health status, shorter hospital stays, and lower hospitalization costs.

Conclusions: The treatment of bivalirudin showed better efficacy and safety as compared to UFH among patients with ACS undergoing PCI at high risk of bleeding in contemporary practice.
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http://dx.doi.org/10.1016/j.biopha.2020.110758DOI Listing
October 2020

Independent and interactive effects of air pollutants and ambient heat exposure on congenital heart defects.

Reprod Toxicol 2021 09 24;104:106-113. Epub 2021 Jul 24.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China. Electronic address:

Accumulating studies have been focused on the independent effects of air pollutants and ambient heat exposure on congenital heart defects (CHDs) but with inconsistent results, and their interactive effect remains unclear. A case-control study including 921 cases and 9210 controls was conducted in Changsha, China in warm season in 2015-2018. The gravidas were assigned monthly averages of daily air pollutants and daily maximum temperature using the nearest monitoring station method and city-wide average method, respectively, during the first trimester of pregnancy. Multivariate logistic regression models were used to estimate the independent effects of each air pollutant and different ambient heat exposure indicators. Their additive joint effects were quantified using attribute proportions of interaction (API). Increasing SO consistently increased the risk of CHDs in the first trimester of pregnancy, with aORs ranging from 1.78 to 2.04. CO, NO and PM exposure in the first month of pregnancy, and O exposure in the second and third month of pregnancy were also associated with elevated risks of CHDs, with aORs ranging from 1.04 to 1.15. Depending on the ambient heat exposure indicator used, air pollutants showed more apparent synergistic effects (API > 0) with less and moderately intense heat exposure. Maternal exposure to CO, NO, SO, PM and O during early pregnancy increased risk of CHDs, and ambient heat exposure may enhance these effects. Our findings help to understand the interactive effect of air pollution with ambient heat exposure on CHDs, which is of vital public health significance.
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http://dx.doi.org/10.1016/j.reprotox.2021.07.007DOI Listing
September 2021

Novel polysaccharide extracted from Sipunculus nudus inhibits HepG2 tumour growth in vivo by enhancing immune function and inducing tumour cell apoptosis.

J Cell Mol Med 2021 Sep 24;25(17):8338-8351. Epub 2021 Jul 24.

Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-Sen University, Guangzhou, China.

A novel polysaccharide was extracted from Sipunculus nudus (SNP). The molecular weight (MW) of SNP was determined to be 9223 Da by high-performance gel permeation chromatography analyses, and the structure of the SNP repeat units was determined to be →3,4-β-D-GlcpNAC (1→ and →4) -α-D-Glcp (1→ in the ratio of 15:1; →2) -α -D-Galp - (1→ as a side chain; and β-D-Galp-(1→ and α- D-Glcp - (1→ as end groups by GC-MS analysis and NMR assays. The effect of SNP on hepatoma HepG2-bearing mice was analysed to verify its potential in the clinical treatment of liver cancer. A total of 90 male athymic nu/nu mice were divided into therapeutic and preventive groups and fed with different amounts of SNP. The antitumour effect of SNP on HepG2-bearing mice and mechanism of such were studied by analysing the tumour size, spleen index, thymus index, immune factors in the blood, tumour apoptosis factors, etc. The results suggest that SNP not only increased the index of immune organs in the body, but also enhanced the secretion of immune factors, including interleukin-2, interferon gamma and tumour necrosis factor-alpha in the serum. SNP induced the apoptosis of tumour cells via the mitochondrial apoptosis pathway, which upregulated caspase-3, caspase-8, caspase-9 and BCL2-associated X, but downregulated B-cell lymphoma-2 and vascular endothelial growth factor protein expression. In conclusion, SNP inhibited tumour growth by enhancing immune function and inducing tumour cell apoptosis in HepG2-bearing mice. Therefore, SNP may be further investigated as a promising candidate for future antitumour drugs.
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http://dx.doi.org/10.1111/jcmm.16793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419178PMC
September 2021

Rotational Dynamics of an Amphidynamic Zirconium Metal-Organic Framework Determined by Dielectric Spectroscopy.

J Phys Chem Lett 2021 Jun 10;12(24):5644-5648. Epub 2021 Jun 10.

Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.

A zirconium metal-organic framework with a difluorophenylene rotator bearing a permanent electric dipole of ∼3.2 D was synthesized, and its rotational motion was analyzed by temperature- and frequency-dependent broadband dielectric spectroscopy. While solid-state NMR confirms fast rotation qualitatively, the dissipation factors measured between 113 and 153 K suggested an activation energy = 2.6 kcal/mol, but deviations from a single Debye relaxation suggested a dynamic process that cannot be accounted for by a well-defined potential with a single activation barrier. The dynamic heterogeneity of the dipolar rotor was confirmed by analysis in terms of a Cole-Cole relaxation, which suggested a mean barrier of ∼1.9 kcal/mol, with a heterogeneity that decreases as temperature increases. Based on the single-crystal structure, we propose that the kinetic heterogeneity results from a temperature-dependent potential where rotation motion is mediated by the escape of the rotator from an energy well created by a double Ph-H···F-Ph hydrogen bond.
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http://dx.doi.org/10.1021/acs.jpclett.1c01333DOI Listing
June 2021

Low bias multiple displacement amplification with confinement effect based on agarose gel.

Anal Bioanal Chem 2021 Jul 28;413(17):4397-4405. Epub 2021 May 28.

State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, Jiangsu, China.

Multiple displacement amplification (MDA) is a popular single-cell whole-genome amplification (WGA) technique that can greatly improve the amplification efficiency of single-cell genomes. However, there is an inherent problem that cannot be completely solved, that is, the amplification bias. We here propose an improved MDA method based on low melting agarose gel, named gelMDA. Firstly, the agarose gel and solution were characterized with SEM and fluorescent reagent. Then, we used gelMDA for cDNA amplification in library preparation of RNA-seq, and conventional MDA was used as a comparison. The sensitivity, efficiency of gelMDA, and amplification bias were evaluated with fluorescence curve, product yield, and the sequencing results. Finally, gelMDA was used for single-cell transcriptome sequencing. The results showed that the sensitivity and product yield of gelMDA were significantly higher than those of conventional MDA. A lower coefficient of variation (CV) and a higher reproducibility were obtained from gelMDA sequencing results. A region of 30 μm in diameter was amplified from the tissue sections and successfully sequenced. In conclusion, gelMDA obtained higher amplification efficiency and lower amplification bias in the present study. It suggested the great potential in single-cell RNA amplification and sequencing.
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http://dx.doi.org/10.1007/s00216-021-03415-3DOI Listing
July 2021

CD14HLA-DR Cells in Patients May Be a Biomarker Reflecting the Progression of COVID-19.

Viral Immunol 2021 Oct 20;34(8):579-581. Epub 2021 May 20.

Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, Harbin, China.

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http://dx.doi.org/10.1089/vim.2021.0009DOI Listing
October 2021

Dissecting Cellular Function and Distribution of β-Glucosidases in Trichoderma reesei.

mBio 2021 05 11;12(3). Epub 2021 May 11.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China

has 11 putative β-glucosidases in its genome, playing key parts in the induction and production of cellulase. Nevertheless, the reason why the genome encodes so many β-glucosidases and the distinct role each β-glucosidase plays in cellulase production remain unknown. In the present study, the cellular function and distribution of 10 known β-glucosidases (CEL3B, CEL3E, CEL3F, CEL3H, CEL3J, CEL1A, CEL3C, CEL1B, CEL3G, and CEL3D) were explored in , leaving out BGL1 (CEL3A), which has been well investigated. We found that the overexpression of or significantly enhanced extracellular β-glucosidase production, whereas the overexpression of severely inhibited cellulase production by cellulose, resulting in nearly no growth of Four types of cellular distribution patterns were observed for β-glucosidases in : (i) CEL3B, CEL3E, CEL3F, and CEL3G forming clearly separated protein secretion vesicles in the cytoplasm; (ii) CEL3H and CEL3J diffusing the whole endomembrane as well as the cell membrane with protein aggregation, like a reticular network; (iii) CEL1A and CEL3D in vacuoles; (iv) and CEL3C in the nucleus. β-glucosidases CEL1A, CEL3B, CEL3E, CEL3F, CEL3G, CEL3H, and CEL3J were identified as extracellular, CEL3C and CEL3D as intracellular, and CEL1B as unknown. The extracellular β-glucosidases CEL3B, CEL3E, CEL3F, CEL3H, and CEL3G were secreted through a tip-directed conventional secretion pathway, and CEL1A, via a vacuole-mediated pathway that was achieved without any signal peptide, while CEL3J was secreted via an unconventional protein pathway bypassing the endoplasmic reticulum (ER) and Golgi. Although β-glucosidases play an important role in fungal cellulase induction and production, our current understanding does not provide a global perspective on β-glucosidase function. This work comprehensively studies all the β-glucosidases regarding their effect on cellulase production and their cellular distribution and secretion. Overexpression of or significantly enhanced β-glucosidase production, whereas overexpression of severely inhibited cellulase production on cellulose. In addition, overexpression of , , , , , , or delayed endoglucanase (EG) production. We first identified four cellular distribution patterns of β-glucosidases in Specially, CEL3C was located in the nucleus. CEL3J was secreted through the nonclassical protein secretion pathway bypassing endoplasmic reticulum (ER) and Golgi. CEL1A was secreted via a vacuole-mediated conventional secretion route without a signal peptide. These findings advance our understanding of β-glucosidase properties and secretory pathways in filamentous fungi, holding key clues for future study.
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http://dx.doi.org/10.1128/mBio.03671-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262880PMC
May 2021

Decreased T Cell Levels in Critically Ill Coronavirus Patients: Single-Center, Prospective and Observational Study.

J Inflamm Res 2021 9;14:1331-1340. Epub 2021 Apr 9.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.

Background: Since Dec. 2019, the COVID-19 pandemic has been an outbreak. T cells play an important role in dealing with various disease-causing pathogens. However, the role of T cells played in COVID-19 patients is still unknown. Our study aimed to describe the immunologic state of the critically ill COVID-19 patients.

Methods: A total of 63 patients with confirmed COVID-19 pneumonia were admitted to the Department of Intensive Care Unit of the First Affiliated Hospital of Harbin Medical University. The immunologic characteristics (lymphocyte apoptosis, the expression of PD-1 and HLA-DR in T cells, T cell subset levels, redistribution and the production of inflammatory factors) as well as their laboratory parameters were compared between severe group and critical group.

Results: The level of T cells in peripheral blood was decreased in critical patients compared with that in severe patients, but the expression levels of PD-1 (CD4: 24.71% VS 30.56%; CD8: 33.05% VS 32.38%) and HLA-DR (T cells: 36.28% VS 27.44%; monocytes: 20.58% VS 23.83%) in T cells were not significantly changed, and apoptosis and necrosis were not different in lymphocytes (apoptosis: 1.04% VS 1.27%; necrosis: 0.67% VS 1.11%), granulocytes, or monocytes between those two groups.

Conclusion: There is severe immunosuppression in critically ill COVID-19 patients. Redistribution of T cells might be the main reason for lymphocytic decline. Decreasing the infiltration of T lymphocytes in the lung may be beneficial for the treatment of COVID-19.
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http://dx.doi.org/10.2147/JIR.S303117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044074PMC
April 2021

Molecular Characterization of the Von Willebrand Factor Type D Domain of Vitellogenin from .

Mar Drugs 2021 Mar 25;19(4). Epub 2021 Mar 25.

Fisheries College, Jimei University, Xiamen 361021, China.

The von Willebrand factor type D (VWD) domain in vitellogenin has recently been found to bind tetrodotoxin. The way in which this protein domain associates with tetrodotoxin and participates in transporting tetrodotoxin in vivo remains unclear. A cDNA fragment of the vitellogenin gene containing the VWD domain from pufferfish ( (TfVWD) was cloned. Using in silico structural and docking analyses of the predicted protein, we determined that key amino acids (namely, Val, ASP, Val, and Lys) in TfVWD mediate its binding to tetrodotoxin, which was supported by in vitro surface plasmon resonance analysis. Moreover, incubating recombinant rTfVWD together with tetrodotoxin attenuated its toxicity in vivo, further supporting protein-toxin binding and indicating associated toxicity-neutralizing effects. Finally, the expression profiling of TfVWD across different tissues and developmental stages indicated that its distribution patterns mirrored those of tetrodotoxin, suggesting that TfVWD may be involved in tetrodotoxin transport in pufferfish. For the first time, this study reveals the amino acids that mediate the binding of TfVWD to tetrodotoxin and provides a basis for further exploration of the molecular mechanisms underlying the enrichment and transfer of tetrodotoxin in pufferfish.
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http://dx.doi.org/10.3390/md19040181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065724PMC
March 2021

Real-to-virtual domain transfer-based depth estimation for real-time 3D annotation in transnasal surgery: a study of annotation accuracy and stability.

Int J Comput Assist Radiol Surg 2021 May 30;16(5):731-739. Epub 2021 Mar 30.

Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong.

Purpose: Surgical annotation promotes effective communication between medical personnel during surgical procedures. However, existing approaches to 2D annotations are mostly static with respect to a display. In this work, we propose a method to achieve 3D annotations that anchor rigidly and stably to target structures upon camera movement in a transnasal endoscopic surgery setting.

Methods: This is accomplished through intra-operative endoscope tracking and monocular depth estimation. A virtual endoscopic environment is utilized to train a supervised depth estimation network. An adversarial network transfers the style from the real endoscopic view to a synthetic-like view for input into the depth estimation network, wherein framewise depth can be obtained in real time.

Results: (1) Accuracy: Framewise depth was predicted from images captured from within a nasal airway phantom and compared with ground truth, achieving a SSIM value of 0.8310 ± 0.0655. (2) Stability: mean absolute error (MAE) between reference and predicted depth of a target point was 1.1330 ± 0.9957 mm.

Conclusion: Both the accuracy and stability evaluations demonstrated the feasibility and practicality of our proposed method for achieving 3D annotations.
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http://dx.doi.org/10.1007/s11548-021-02346-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134290PMC
May 2021

Effects of sacubitril/valsartan on clinical symptoms, echocardiographic parameters, and outcomes in HFrEF and HFmrEF patients with coronary heart disease and chronic kidney disease.

Curr Med Res Opin 2021 07 20;37(7):1071-1078. Epub 2021 Apr 20.

Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China.

Objective: To compare the effects of Angiotensin Receptor-Neprilysin inhibitor (ARNI) on the clinical symptoms, echocardiographic parameters, and outcomes (cardiovascular death and hospitalization) in heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF) patients with coronary heart disease and chronic kidney disease.

Method: A retrospective observational study was conducted from January 2018 to May 2019, with a follow-up period of 95.4 ± 57.8 days (8 months). Data from 127 patients were included.

Results: A statistically significant increase of 68.8% was observed in left ventricular ejection fraction (LVEF) in HFrEF patients compared to that in HFmrEF patients, with an increase of 27.2% at 8 months of follow-up. Sacubitril/valsartan significantly reduced left ventricular end-systolic volumes (LVESV) in HFrEF patients unlike in HFmrEF patients. The decrease in LVESV was 28.8% in HFrEF patients and 17.1% in HFmrEF patients. A significant reduction in the prevalence of severe secondary mitral regurgitation (EROA > 0.4 cm) was observed in HFrEF compared to that in HFmrEF patients with the use of sacubitril/valsartan. A reduction of 15.6% was observed in HFrEF patients, whereas a reduction of 7.1% was observed in HFmrEF patients. Improvement in functional classification (NYHA) was observed during follow-up. The prevalence of (NYHA III) reduced from 50% to 15.7% in HFrEF patients, whereas a reduction from 21.1% to 8.8% was observed in HFmrEF patients. There was a significant reduction in NT-proBNP in HFrEF patients compared to that in HFmrEF patients. A reduction of 52% was observed in HFrEF patients, whereas a reduction of 28.7% was observed in HFmrEF pateints. Sacubitril/valsartan reduced primary endpoint events in both groups. The prevalence of HF-related hospitalization was higher in HFrEF than in HFmrEF patients: 12.1% vs 7.5%, respectively. The prevalence of CV death in HFrEF vs HFmrEF patients was 3.7% vs 0.5%, respectively. Cardiovascular (CV) death was higher in patients with atrial fibrillation in both groups.

Conclusion: Sacubitril/valsartan significantly improved morphofunctional remodeling parameters and clinical symptoms in HFrEF patients than in HFmrEF patients.
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http://dx.doi.org/10.1080/03007995.2021.1908243DOI Listing
July 2021

The 11th International Workshop on Modeling the Ocean (IWMO 2019) in Wuxi, China, on June 17-20, 2019.

Ocean Dyn 2021 Feb 27:1-4. Epub 2021 Feb 27.

Department of Atmospheric and Oceanic Sciences, Peking University, Beijing, People's Republic of China.

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http://dx.doi.org/10.1007/s10236-021-01448-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910755PMC
February 2021

Monitoring minimal/measurable residual disease in B-cell acute lymphoblastic leukemia by flow cytometry during targeted therapy.

Int J Hematol 2021 Mar 27;113(3):337-343. Epub 2021 Jan 27.

Central Laboratory of Hematology and Oncology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy of B-type lymphoid precursor cells. Minimal/measurable residual disease (MRD) is an important prognostic factor for B-ALL relapse. Traditional flow cytometry detection mainly relies on CD19-based gating strategies. However, relapse of CD19-negative B-ALL frequently occurs in patients who receive cellular and targeted therapy. This review will summarize the technical aspects of standard MRD assessment in B-ALL by flow cytometry, and then discuss the challenges of MRD strategies to deal with the scenario of CD19 negative or dim B-ALL relapse.
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http://dx.doi.org/10.1007/s12185-021-03085-yDOI Listing
March 2021

Performance-aware programming for intraoperative intensity-based image registration on graphics processing units.

Int J Comput Assist Radiol Surg 2021 Mar 23;16(3):375-386. Epub 2021 Jan 23.

Department of Mechanical Engineering, The University of Hong Kong, Pok Fu Lam, Hong Kong.

Purpose: Intensity-based image registration has been proven essential in many applications accredited to its unparalleled ability to resolve image misalignments. However, long registration time for image realignment prohibits its use in intra-operative navigation systems. There has been much work on accelerating the registration process by improving the algorithm's robustness, but the innate computation required by the registration algorithm has been unresolved.

Methods: Intensity-based registration methods involve operations with high arithmetic load and memory access demand, which supposes to be reduced by graphics processing units (GPUs). Although GPUs are widespread and affordable, there is a lack of open-source GPU implementations optimized for non-rigid image registration. This paper demonstrates performance-aware programming techniques, which involves systematic exploitation of GPU features, by implementing the diffeomorphic log-demons algorithm.

Results: By resolving the pinpointed computation bottlenecks on GPU, our implementation of diffeomorphic log-demons on Nvidia GTX Titan X GPU has achieved ~ 95 times speed-up compared to the CPU and registered a 1.3-M voxel image in 286 ms. Even for large 37-M voxel images, our implementation is able to register in 8.56 s, which attained ~ 258 times speed-up. Our solution involves effective employment of GPU computation units, memory, and data bandwidth to resolve computation bottlenecks.

Conclusion: The computation bottlenecks in diffeomorphic log-demons are pinpointed, analyzed, and resolved using various GPU performance-aware programming techniques. The proposed fast computation on basic image operations not only enhances the computation of diffeomorphic log-demons, but is also potentially extended to speed up many other intensity-based approaches. Our implementation is open-source on GitHub at https://bit.ly/2PYZxQz .
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http://dx.doi.org/10.1007/s11548-020-02303-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946684PMC
March 2021

BTF3 confers oncogenic activity in prostate cancer through transcriptional upregulation of Replication Factor C.

Cell Death Dis 2021 01 5;12(1):12. Epub 2021 Jan 5.

Cancer Institute, Department of Urology, The Second Hospital of Dalian Medical University; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.

High levels of Basic Transcription Factor 3 (BTF3) have been associated with prostate cancer. However, the mechanisms underlying the role of BTF3 as an oncogenic transcription factor in prostate tumorigenesis have not been explored. Herein, we report that BTF3 confers oncogenic activity in prostate cancer cells. Mechanistically, while both BTF3 splicing isoforms (BTF3a and BTF3b) promote cell growth, BTF3b, but not BTF3a, regulates the transcriptional expression of the genes encoding the subunits of Replication Factor C (RFC) family that is involved in DNA replication and damage repair processes. BTF3 knockdown results in decreased expression of RFC genes, and consequently attenuated DNA replication, deficient DNA damage repair, and increased G2/M arrest. Furthermore, knockdown of the RFC3 subunit diminishes the growth advantage and DNA damage repair capability conferred by ectopic overexpression of BTF3b. Importantly, we show that enforced BTF3 overexpression in prostate cancer cells induces substantial accumulation of cisplatin-DNA adducts and render the cells more sensitive to cisplatin treatment both in vitro and in vivo. These findings provide novel insights into the role of BTF3 as an oncogenic transcription factor in prostate cancer and suggest that BTF3 expression levels may serve as a potential biomarker to predict cisplatin treatment response.
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http://dx.doi.org/10.1038/s41419-020-03348-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791038PMC
January 2021

Chromosomal abnormality: Prevalence, prenatal diagnosis and associated anomalies based on a provincial-wide birth defects monitoring system.

J Obstet Gynaecol Res 2021 Mar 28;47(3):865-872. Epub 2020 Dec 28.

NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China.

Aim: To investigate the epidemiology of chromosomal abnormalities (CA) in fetuses of all pregnancies based on a provincial-wide birth defects-monitoring system, which could provide scientific basis for making relatively policy and research.

Methods: Chromosomal abnormalities cases were collected from all hospitals in Hunan Province, China, between 2016 and 2019. The prevalence of CAs was calculated to examine associations among infant sex, maternal age and region. The rates of prenatal diagnosis and termination of pregnancy (TOP) involving CA or associated anomalies were calculated as rates or proportions.

Results: From 2016 to 2019, a total of 2 883 890 perinatal infants (28 weeks of gestation to postpartum 7 days) underwent prenatal screening and diagnostic tests, and 3181 fetuses were diagnosed as CA, with the prevalence of 11.03/10 000. The average prevalence of CAs was higher for male than female fetuses (11.33/10 000 vs 10.06/10 000) (OR = 1.13, 95% CI: 1.05-1.21), which was higher in urban areas than rural areas (23.03/10 000 vs 7.13/10 000) (OR = 3.23, 95% CI: 3.02-3.47), and the prevalence increased linearly with maternal age ( = 1821.844, P = 0.000). Among the fetuses with CAs, 3097 (97.36%) were diagnosed prenatally, and 3046 (98.35%) underwent TOP. The majority of CA were numerical abnormalities (90.18%). The main types of numerical autosomal abnormalities were trisomy 21 (6.69/10 000, 59.57%), trisomy 18 (1.13/10 000, 10.04%) and trisomy 13 (0.21/10 000, 1.88%). The main types of numerical gonosomal abnormalities were Klinefelter syndrome (0.68/10 000, 6.02%), Turner syndrome (0.49/10 000, 4.39%), Triple X syndrome (0.26/10 000, 2.29%) and 47,XYY syndrome (0.21/10 000, 1.91%). The three associated anomalies with the highest proportions were congenital heart defects (CHD) (41.06%), cleft palate or/and cleft lip (10.89%) and congenital talipes equinovarus (8.94%).

Conclusion: The prevalence of CA was lower than that reported. Chromosome detection should be further promoted including test contest and coverage, especially for urban areas, older mothers and fetuses with CHD, cleft palate or/and cleft lip or congenital talipes equinovarus.
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http://dx.doi.org/10.1111/jog.14569DOI Listing
March 2021

Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes.

Front Immunol 2020 4;11:568741. Epub 2020 Dec 4.

Central Laboratory, First Affiliated Hospital, Harbin Medical University, Harbin, China.

Cytokine cascades exist in many autoimmune disorders which amplify and sustain the autoimmune process and lead to chronic inflammatory injury to the host tissues. Increasing evidence indicates that chondrocytes can interact with T cells, which may be a crucial event in inflammatory arthritis. To address the reciprocal influences of cartilage-reactive T cells and chondrocytes, we constructed cartilage-reactive T cells by developing a type II collagen-specific chimeric antigen receptor (CII-CAR). An co-culture model of CII-CAR-T cells and fresh cartilage was developed, in which CII-CAR-T displayed specific proliferative capacity and cytokine release against fresh cartilage samples, and chondrocytes could respond to CII-CAR-T cells by secreting IL-6. The proposed model will help us to explore the possible cytokine cascades between cartilage-reactive T cells and cartilage.
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http://dx.doi.org/10.3389/fimmu.2020.568741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746615PMC
May 2021
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