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Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P＜0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P＜0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P＜0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P＜0.05).There was no significant difference between Fer-1 group and con-trol group(P＜0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P＜0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.
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Objective To analyze the relationship of the volume of 87 brain regions with postnatal age and neurobehavior in full-term neonates.Methods A total of 75 full-term newborns[gestational age(39.38±1.22)weeks;male/female(51/24);postnatal age(11.11±6.67)days]without abnormalities on brain MRI(three-dimensional T1-weighted imaging,3D T1WI)at our hospital between November 2010 and September 2017 were retrospectively included.Based on the template of 87 brain regions,the neonatal brains were divided into 87 brain regions and their volumes were calculated by using V-shape Bottleneck network(VB-Net)deep learning segmentation technique,Pearson partial correlation and regression analysis were used to explore the relationship of the volume of each brain region with postnatal age and neurobehavioral scores.Results After adjusting for gestational age,birth weight,head circumference,body length and sex,66.7％of the regional brain volumes(58/87 brain regions)significantly increased with the postnatal age(correlation coefficient r:0.2-0.7,P＜0.05).The volumes of gray matter in bilateral lentiform nucleus,left caudate nucleus,right occipital lobe,right inferior temporal lobe,and bilateral anterior temporal lobe strongly correlated with the postnatal age(r＞0.50,P＜0.05).The gray matter volume of the right occipital lobe linearly increased with age(slope:100.67),and was positively correlated with behavioral scores(r=0.324,P＜0.01).Conclusion Most of regional brain volumes increase with the postnatal age during the neonatal period,and the fastest growth occurs in primary sensorimotor-related brain regions,presenting the spatial heterogeneity.Partial brain region grows with the development of behavioral ability.
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Objective To explore the effect of exposure to noise of 3.0T magnetic resonance imaging(MRI)on children's cochlear function.Methods We prospectively recruited 72 children who underwent cranial MRI examination at our hospital from May to November 2018;3M earplugs and sponge mats were used for hearing protection during MRI scanning.Noise level(dBA)of each MRI sequence was detected with a nonmagnetic microphone and a sound level meter.Distortion product otoacoustic emissions(DPOAE)test at 2-7 kHz was performed 24 hours before and 30 minutes after the MRI examination.Paired t-test or Wilcoxon signed-rank test was used to analyze differences in DPOAE amplitude before and after the MRI examination.Results The average noise level of MRI measured in the study was(107.7±3.92)dBA.Compared with that before the MRI examination,the DPOAE amplitude(dB)changed little after the MRI examination;the range of amplitude differences in each age group was as follows:left ear(-0.24-1.10)and right ear(-0.24-0.74)in the 0-1 year-old group;left ear(-0.07-0.59)and right ear(-0.57-0.75)in the 2-5 year-old group;left ear(-0.36-0.44)and right ear(-0.30-0.57)in the 6-12 year-old group.No statistically significant difference was found(correction P＞0.05).Conclusion No potential impact of 3.0T MRI noise on children's cochlear function was observed under routine hearing protection.
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Objective:To investigate the predictive value of a radiomics model based on biparametric magnetic resonance imaging(bpMRI)for biochemical recurrence(BCR)after radical prostatectomy(RP)in elderly prostate cancer patients(≥60 years old).Methods:A retrospective analysis was conducted on data from 175 patients treated at Beijing Hospital from August 2017 to December 2021.Based on pathological results, image segmentation was performed on preoperative bpMRI T2, diffusion weighted imaging(DWI), and apparent diffusion coefficient(ADC)sequences.Pyradiomics was utilized to extract radiomic features, and Cox regression, Spearman correlation coefficient, and LASSO regression were employed for feature dimensionality reduction, leading to the construction of radiomic labels.Clinical models and image-clinical combined models were developed using multifactorial Cox regression analysis, and the performance of these models in predicting BCR was evaluated using the concordance index(C-index).Results:The 175 patients were randomly divided into a training set(122 cases)and a test set(53 cases)at a ratio of 7∶3, with 24 cases(19.7%, 24/122)and 11 cases(20.8%, 11/53)experiencing BCR, respectively.A total of 5 775 radiomic features were extracted from the three sequences, and after dimensionality reduction, 5 features were selected to construct the radiomic labels.The radiomics model exhibited C-index values of 0.764(95% CI: 0.655-0.872)and 0.769(95% CI: 0.632-0.906)in the training and test sets, respectively.Multifactorial Cox regression analysis revealed serum prostate-specific antigen(PSA)( HR=1.032, 95% CI: 1.010-1.054), postoperative pathology International Society of Urological Pathology(ISUP)grade grouping( HR=1.682, 95% CI: 1.039-2.722), and positive surgical margins( HR=2.513, 95% CI: 1.094-5.774)as independent predictors of BCR.The clinical model exhibited C-index values of 0.751(95% CI: 0.655-0.846)and 0.753(95% CI: 0.630-0.877)in the training and test sets, respectively.Following combined modeling of clinical factors and radiomic labels, the image-clinical combined model demonstrated the highest C-index values, namely 0.782(95% CI: 0.679-0.874)and 0.801(95% CI: 0.677-0.915)in the training and test sets, respectively. Conclusions:The radiomics model based on bpMRI can predict the occurrence of BCR after RP in elderly prostate cancer patients.Combined modeling of clinical factors and radiomic labels can enhance predictive efficiency.
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With the rapid development of science and technology and the wide application of electronic products, the number of patients with high myopia is gradually increasing. Meanwhile, owing to the continuous optimization of surgical skils and the continuous advancement in materials of posterior chamber intraocular lens and manufacturing processes, implantable collamer lens(ICL)V4c implantation has gradually become one of the main surgeries for the treatment of high myopia. In the rapid era of social information, people pay more attention to the long-term efficacy after ICL V4c implantation, they not only want clear vision, but also the pursuit of visual comfort and durability. Therefore, this paper will specifically discuss the research progress of the post-implantation efficacy of ICL V4c with at least 2 a of follow-up observation within 3 a, aiming to review the latest research progress on the long-term efficacy of ICL V4c implantation from the three dimensions of visual quality, safety, efficacy and stability and possible surgical complications after ICL V4c implantation.
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Objective To explore the effect of process rehabilitation nursing on the joint range of motion,grip strength,replantation survival rate and functional recovery of severed fingers after replantation.Methods A total of 70 patients undergoing replantation of severed fingers who were admitted to Linping District,the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2019 to December 2022 were selected.The patients were divided into the control group(n=35)with routine nursing,and the research group(n=35)with routine rehabilitation nursing,and the nursing effects of the two groups were compared.Results After nursing,the excellent and good rate of the research group was 97.14％(34/35),which was significantly higher than that of the control group was 82.86％(29/35)(P<0.05);After nursing,the range of motion,grip strength,replantation survival rate and functional score of the finger joint in the study group were higher than those in the control group(P<0.05);After 3 months of nursing,the excellent and good rate of joint range of motion in the study group was 94.29％(33/35),which was significantly higher than that in the control group was 74.29％(26/35)(P<0.05).Conclusion The application of process rehabilitation nursing in patients with replantation of severed fingers has significantly improved joint activity and restored the function of severed fingers,which can be popularized.
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INTRODUCTION: Circulating cell-free DNA (cfDNA) is a good diagnostic tool for hepatocellular carcinoma as it can comprehensively reflect the heterogeneity of tumors and aid in their early detection. This study aimed to assess the diagnostic value of circulating cfDNA for hepatocellular carcinoma. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases were searched to identify all relevant literature from their dates of establishment to 6 April 2022, and a total of 2,467 articles were found. Methodological quality assessment was performed using QUADAS-2. RESULTS: Fifteen articles with 3,686 patients were included in this study after screening. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.83 (95% confidence interval [CI]: 0.78, 0.87), 0.90 (95% CI: 0.86, 0.93), 8.4 (95% CI: 5.9, 12.0), 0.19 (95% CI: 0.15, 0.24), 44 (95% CI: 30, 66), and 0.93 (95% CI: 0.90, 0.95), respectively. Deek's funnel plot test did not show significant publication bias (P = 0.28). CONCLUSIONS: Results of this meta-analysis suggest that circulating cfDNA has moderate sensitivity and excellent specificity for the detection of hepatocellular carcinoma as a noninvasive test (0.83 and 0.90, respectively).
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Carcinoma, Hepatocellular , Cell-Free Nucleic Acids , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Odds Ratio , DNA , ROC Curve , Sensitivity and SpecificityABSTRACT
Objective:To explore the asymmetry of neonatal brain white matter using fractional anisotropy (FA) parameter generated from diffusion tensor imaging (DTI).Methods:From January 2011 to June 2013, 88 neonates with normal cranial MRI performance, aged 1-14 (7.7±0.3) days and gestational age 31-42 (37.5±0.3) weeks, were retrospectively collected from the First Affiliated Hospital of Xi′an Jiaotong University. According to the gestational age at birth, the neonates were divided into preterm group (37 cases) and term group (51 cases). DTI was processed to generate FA parametric maps. Tract-based spatial statistics (TBSS) was used to analyze the asymmetry in neonatal white matter. Regions of interest were placed in bilaterally symmetrical white matter tracts. The white matter tracts included the bilateral anterior thalamic radiation, corticospinal tract-posterior limb of the inner capsule (CST-IC), corticospinal tract-corona radiata, cingulum hippocampus part (CGH), inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus, superior longitudinal fasciculus temporal part (SLF-temp). The FA value was measured and asymmetry index (AI) was calculated. The independent-sample t test or Mann-Whitney U test was used to compare the AI of each tract between the preterm and term groups. Partial correlation was used to analyze the effects of neonatal gestational age and birth anthropometric measures on the asymmetry of neonate at birth. Results:The results of TBSS showed that the left lateralized areas of brain white matter in the neonatal period were mainly located in the corticospinal tract, external capsule and genu of corpus callosum. The right lateralized areas of brain white matter in the neonatal period were mainly located in the optic radiation and splenium of corpus callosum. In both the preterm and term groups, the tracts related to motor (CST-IC) and language function (ILF, SLF, SLF-temp) were left asymmetry. The CGH of the preterm and the term neonates were right asymmetry, and AI was -0.086±0.114 and -0.140±0.108 respectively, with a statistically significant difference ( t=2.27, P=0.026), while the differences of AI in the remaining tracts were not statistically significant ( P>0.05). Only gestational age was correlated with the AI of ILF ( r=0.234, P=0.033), SLF ( r=0.259, P=0.018), SLF-temp ( r=0.252, P=0.022), CST-IC ( r=0.235, P=0.033). No significant correlation was found between birthweight, head circumference, body length and AI. Conclusions:The asymmetries of brain white matter already exist in neonates aged less than two weeks. The tracts associated with motor and language function are predominantly left asymmetry.
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BACKGROUND@#This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.@*METHODS@#First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.@*RESULTS@#A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).@*CONCLUSION@#The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
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Humans , Case-Control Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , RNA, Long Noncoding/genetics , Silicosis/geneticsABSTRACT
Objective:To study the relationship between white matter injury (WMI) and brain maturity in preterm infants at full-term corrected gestational age (cGA).Methods:A retrospective study was performed in preterm infants [GA≤32 weeks or birth weight (BW) ≤1 500 g] admitted to the neonatal intensive care unit of the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to August 2018 and the Northwest Women and Children's Hospital from January 2017 to June 2017. The infants received conventional magnetic resonance imaging (MRI) at cGA 37~42 weeks. The infants were assigned into the WMI group and the control group according to the WMI scoring system, including the total maturation scores (TMS) and four sub-item scores.Results:A total of 118 premature infants were enrolled in this study (17 cases in the WMI group and 101 cases in the control group). The GA was (30.3±1.7) weeks, and BW was (1 356±268) g. The proportion of delayed TMS in the WMI group was significantly higher than the control group [58.8%(10/17) vs. 31.7%(32/101), P<0.05]. The TMS of the WMI group were significantly lower than the control group [(10.7±1.8) vs. (11.8±1.5), P<0.05]. The sub-item scores of TMS showed that the myelination [(2.8±0.6) vs. (3.1±0.4), P<0.05] and glial cell migration bands of the WMI group [(1.6±0.4) vs. (2.1±0.6), P=0.004] were significantly lower than the control group and no significant differences existed in cortical folding and involution of germinal matrix tissue scores between the two groups. Conclusions:The brain maturity of preterm infants with WMI is substantially delayed than those without WMI, including delayed myelination and delayed disappearance of glial cell migration bands.
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The impact of parental obesity on offspring health attracts increasing attention with the rising obese population worldwide. Much more studies have concentrated on the influences of maternal obesity, while studies regarding paternal obesity were relatively few and mainly focused on glucose and insulin regulation, adiposity, etc. Several large cohort studies and animal experiments have shown that paternal obesity can damage the neuropsychological development in offspring, which has become a risk factor for autistic spectrum disorders, cognitive disorders, and lower intelligence quotient, and epigenetic studies have explored the related mechanisms. This review summarizes the progress in this field, aiming to provide a reference for basic and clinical research in the future.
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A 65-year-old male patient, who had a history of chronic lymphocytic leukemia for 3 years, presented with erythematous swelling of the right cheek for 20 days and scattered papules on the back and upper extremities for 10 days. Twenty days prior to the presentation, the patient was hospitalized for disseminated herpes zoster. Skin examination showed diffuse dark red swollen plaques in the facial area under the right eyelid as well as on the right auricle and external acoustic meatus, with a sense of infiltration on palpation; scattered brown crusts were left behind at the sites of healed herpes zoster lesions, and scattered depressed scars were observed among these crusts; scattered infiltrative, mung bean- to soybean-sized, light red papules with a smooth surface were seen on the back of the neck, back and upper limbs. Histopathological examination of the facial skin lesions revealed nodular infiltration of epithelioid cells, lymphocytes and many multinucleated giant cells in the dermis and subcutaneous adipose tissue; immunohistochemical staining showed positive staining for CD68, CD20, CD79a, CD3, CD2, CD10, CD5 and Bcl-2, scattered positive staining for Ki-67, and negative staining for CD23, cyclin D1, Bcl-6, multiple myeloma oncogene 1, CD21, CD35 and myeloperoxidase. The patient was diagnosed with Wolf′s isotopic response manifesting as granulomatous inflammation after disseminated herpes zoster. The patient was treated with intravenous drips of methylprednisolone at a dose of 40 mg/d, and the skin lesions were gradually improved and subsided. No recurrence was observed during 4 years of follow-up.
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OBJECTIVE@#To study the safety of alginate based gastric mucosal protective adhesive and its feasibility as a submucosal injection.@*METHODS@#The feasibility of using alginate-based gastric mucosal protective gel as submucosal injection was evaluated by @*RESULTS@#After injection of different concentrations of alginate base mucosal protective adhesive solution, the uplift height was significantly higher than that of normal saline (@*CONCLUSIONS@#Gastric mucosa protector is a promising new medical device product with feasibility and good biocompatibility as submucosal uplift injection agent.
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Animals , Rats , Adhesives , Alginates , Feasibility Studies , Gastric Mucosa , Injections , SwineABSTRACT
Silk fibroin has the characteristics of good biocompatibility, mechanical properties, degradation performance and easy shaping, which makes silk fibroin become the focus of biomedical material preparation and research, and has received extensive attention. This article reviews the prior art methods of silk fibroin degumming, dissolution and regeneration processing. The specific applications of silk fibroin materials in the field of biomedical materials are reviewed, and the application prospects of silk fibroin in the field of biomedical materials are prospected.
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Biocompatible Materials , FibroinsABSTRACT
The stability of virus-like particles (VLPs) is currently the main factor affecting the quality of foot-and-mouth disease VLPs vaccines. In order to further improve the quality of the VLPs vaccine of foot-and-mouth disease (FMD), three amino acid modification sites were designed and screened through kinetic analysis software, based on the three-dimensional structure of FMDV. The three mutant recombinant plasmids were successfully prepared by the point mutation kit, transformed into Escherichia coli strain BL21 and expressed in vitro. After purification by Ni ion chromatography column, SDS-PAGE proved that the three amino acid mutations did not affect the expression of the target protein. The results of the stability study of three FMD mutant VLPs obtained by in vitro assembly show that the introduction of internal hydrophobic side chain amino acids made the morphology of VLPs more uniform (N4017W), and their stability was significantly improved compared to the other two VLPs. The internal hydrophobic force of the capsid contributes to the formation of VLPs and helps to maintain the stability of the capsid, providing new experimental ideas for improving the quality of VLPs vaccines, and helping to promote the development of VLPs vaccines.
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Animals , Amino Acids , Capsid Proteins/genetics , Foot-and-Mouth Disease/prevention & control , Foot-and-Mouth Disease Virus/genetics , Kinetics , Vaccines, Virus-Like Particle/genetics , Viral Vaccines/geneticsABSTRACT
Objective:To investigate the prognostic significance of the lymphovascular invasion (LVI) in patients with upper tract urothelial carcinoma(UTUC) after radical nephoureterectomy (RNU) and Gemcitabine and Cisplatin combination Chemotherapy (GC).Methods:The clinical data of 95 patients with UTUC admitted to Beijing Friendship Hospital, Capital Medical University from March 2013 to March 2019 were analyzed retrospectively. There were 50 males and 45 females; the average age was 63 years, ranged from 36 to 81 years. According to the situation of LVI, they were divided into LVI positive group ( n=25) and LVI negative group ( n=70). Chi-square test was used to analyze the clinicopathological parameters of the two groups of patients. Kaplan-Meier method was used to draw the survival curves of the overall survival (OS) time and recurrence-free survival (RFS) time of the two groups of patients. The difference between the two groups was used Log-Rank test. The risk factors related to OS and RFS were evaluated using univariate and multivariate Cox regression models. Results:All patients were followed up for 2-82 months, with an average follow-up time of 36 months. Among them, 20(21.1%) died and 36(37.9%) relapsed. There were significant differences in T stage ( P=0.046), lymph node metastasis ( P=0.032), and tumor location ( P=0.019) between LVI negative group and LVI negative group. Univariate analysis showed that hydronephrosis ( P=0.026), lymph node metastasis( P=0.001), LVI ( P=0.001), chemotherapy cycle ( P=0.045) were correlated with OS; hydronephrosis ( P=0.031), tumor T stage ( P=0.013), lymph node metastasis ( P=0.004), LVI ( P=0.001) were significantly correlated with RFS. Multivariate analysis showed that hydronephrosis ( P=0.016), lymph node metastasis ( P=0.016), and LVI( P=0.003) were significantly correlated with OS. Lymph node metastasis ( P=0.018), LVI ( P=0.003) were significantly correlated with RFS. In conclusion, LVI was an independent risk factor for OS and RFS. The OS [(40.7±6.5) months for LVI positive group, (68.5±3.2) months for LVI negative group, χ2=15.750, P<0.001] and RFS [(31.0±5.7) months for LVI positive group, (58.0±8.8) months for LVI negative group, χ2=10.986, P=0.001] of patients with LVI positive group were worse than those with LVI negative group, the differences were statistically significant. Conclusions:LVI is more likely to be possitive in patients with high T stage, lymph node metastasis and single renal pelvis cancer, which provides a basis for risk stratification of patients with UTUC. After radical resection and adjuvant chemotherapy, the benefit of OS and RFS in patients with positive LVI was significantly worse than that in patients with negative LVI.
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Objective:To explore the risk factors of tumor recurrence after radical nephroureterectomy combined with Gemcitabine and Cisplatin(GC) systemic intravenous chemotherapy for upper tract urothelial carcinoma (UTUC), establish a recurrence risk prediction model, and conduct preliminary verification.Methods:One hundred and one cases of UTUC were analyzed from January 2013 to October 2019 in Beijing Friendship Hospital, Capital Medical University retrospectively. All patients underwent radical nephroureterectomy+ bladder cuff resection, and were treated with GC intravenous adjuvant chemotherapy, among which 19 underwent preoperative neoadjuvant chemotherapy. The study collected general information and clinical characteristics of the patients, and follow up the patient's recurrence. Tumor recurrence and relapse free survival (RFS) were the main observation indexes. The patients were divided into the recurrent group and the non-recurrent group according to their recurrence. Kaplan-Meier and Log-rank methods were used to estimate and compare the RFS rates of the two groups. Univariate difference analysis was used to identify the indicators that were significantly different between patients in the recurrence group and the non-recurrence group, and the COX proportional hazard model was further used to explore the correlation between each factor and the tumor recurrence. According to the weights of relevant risk factors, an individual prognostic index (PI) equation was established, a recurrence prediction model was constructed, and the receiver operating characteristic (ROC) curve was used for verification.Results:One hundred and one patients were followed up for 2-82 months, with median 22 months. 40 patients had recurrence, including 32 in the bladder and 8 in the contralateral upper urinary. One-year RFS was 82.10%, two-year RFS was 68.90% and 5-year RFS was 42.10%. COX proportional risk model results showed that tumor hydronephrosis (X1), lymphovascular invasion (X2) and tumor T stage (X3) were independent risk factors, while neoadjuvant chemotherapy (X4) and chemotherapy cycle (X5) were independent protective factors. Individual PI equation =0.964X1+ 0.688X2+ 0.508X3-1.566 X4-0.675X5. The ROC curve was drawn to show that the optimal pointcut value was 179.5 when the Youden index was 0.537, the sensitivity of the model was 0.750, the specificity was 0.787, and the area under the curve (AUC) was 0.838(95% CI: 0.758-0.918). Conclusions:Hydronephrosis, tumor T stage, lymphovascular invasion, neoadjuvant chemotherapy and chemotherapy cycle are independent factors affecting the recurrence of UTUC patients. The multi-factor risk prediction model is suitable for evaluating the possibility of tumor recurrence after radical surgery combined with GC chemotherapy in UTUC patients, which can provide scientific evidence for the prognosis assessment of patients.
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Objective:To explore the mediating effect of self-perceived aging between family care and quality of life (QOL) of elderly type 2 diabetes patients, and to provide the evidence for improving the QOL of elderly type 2 diabetes patients.Methods:The convenience sampling method was used to investigate 215 elderly patients with type 2 diabetes by using the Brief Ageing Perceptions Questionnaire, the Family APGAR Index and the Diabetes Specific Quality of Life Scale, and statistical analysis was performed using SPSS20.0 software.Results:The self-perceived aging score of the elderly patients with type 2 diabetes was (49.90±12.11), the family care score was (7.17±2.53), and the QOL score was (65.89± 12.07). Family care score was negatively correlated with QOL score in elderly patients with type 2 diabetes ( r value was -0.480, P<0.01), self-perceived aging score was negatively correlated with family care score ( r value was -0.472, P<0.01), and positively correlated with QOL score ( r value was 0.688, P<0.01). The mediating effect test showed that self-perceived aging played a complete mediating role between family care and QOL in elderly type 2 diabetes patients, and the mediating effect accounted for 86.51% of the total effect. Conclusions:Self-perceived aging is the mediating variable of family care and QOL, and establishing positive self-perceived aging is conducive to improving the QOL of elderly patients with type 2 diabetes.
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Objective:To investigate the relationship between YES-related protein 1(YAP1)and prostate-specific antigen(PSA)in human castration-resistant prostate cancer(CRPC), and explore the regulation mechanism of YAP1 on PSA.Methods:The luciferase reporter gene was used to detect the activity change of the PSA gene promoter region after the over expression of YAP1 in LNCaP and C4-2 cells.The effect of over expression of YAP1 gene on PSA protein in different prostate cancer cell lines was detected by Western blot(WB)method, and the effect of YAP1 silencing on PSA protein in C4-2 cells was observed.The Q-PCR method was used to further verify the expression change of PSA mRNA affected by YAP1 gene over expressed in C4-2 cells.Meanwhile, WB was used to explore the effect of YAP1 on androgen receptor(AR)in C4-2 cells.Results:After over expression YAP1 in CRPC, the luciferase experiment showed that the average C4-2 cell ratio of experimental group to control group was 3.17815892(>2 times, P<0.001). After Q-PCR detection of all over-expressed YAP1 gene fragments, the measured PSA mRNA values in the experimental groups were 2.306667, 1.553333333, 2.613333333, and 2.673333333, respectively, which were higher than those in the control group(1 time, P<0.001), indicating that the PSA expression was significantly increased.WB analysis showed that after C4-2 cells over expressed YAP1, the AR band was significantly enhanced in the experimental group compared with the control group, suggesting that the AR protein expression in the nucleus was significantly increased in the YAP1 over expression group. Conclusions:YAP1 might positively regulate the PSA expression in CRPC and have an ability to promote AR translocation into the nucleus.
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Surfactin has great potential applications in enhancing oil recovery, agriculture, pharmaceuticals, foods and beverages, and cosmetics due to its extraordinary surface activity, biodegradability, anti-bacterial activity and biocompatibility. Enhancing surfactin production by engineering surfactin-producer and optimizing culture conditions is the key of its industrial production and subsequent applications. In this study, the effect of fatty acid synthesis pathway on surfactin synthesis was investigated, and Bacillus subtilis THBS-2 and THBS-8 with high surfactin titer were constructed by overexpressing key genes involved in the fatty acid synthesis pathway. To optimize culture condition, the amount and adding time of isopropyl-beta-D-thiogalactopyranoside (IPTG) and amino acids were studied, and a two-stage culture method was obtained: IPTG (final concentration: 1.25 mmol/L) and leucine (final concentration: 5 g/L) were added at 3 h, leucine (final concentration 5 g/L) and condensed culture medium (5 mL) were added at 24 h. Applying this strategy, the surfactin titer of B. subtilis THBS-2 reached to 24 g/L in shake flask at 48 h and up to 34 g/L after 68 h fermentation in a 30-L fermentor. The results provide basis for large-scale production and broad application of surfactin.