OBJECTIVES: Long-term elevated blood pressure may lead to kidney damage, yet the pathogenesis of hypertensive kidney damage is still unclear. This study aims to explore the role and significance of leucine-rich alpha-2-glycoprotein-1 (LRG-1) in hypertensive renal damage through detecting the levels of LRG-1 in the serum and kidney of mice with hypertensive renal damage and its relationship with related indexes. METHODS: C57BL/6 mice were used in this study and randomly divided into a control group, an angiotensin II (Ang II) group, and an Ang II+irbesartan group. The control group was gavaged with physiological saline. The Ang II group was pumped subcutaneously at a rate of 1.5 mg/(kg·d) for 28 days to establish the hypertensive renal damage model in mice, and then gavaged with equivalent physiological saline. The Ang II+irbesartan group used the same method to establish the hypertensive renal damage model, and then was gavaged with irbesartan. Immunohistochemistry and Western blotting were used to detect the expression of LRG-1 and fibrosis-related indicators (collagen I and fibronectin) in renal tissues. ELISA was used to evaluate the level of serum LRG-1 and inflammatory cytokines in mice. The urinary protein-creatinine ratio and renal function were determined, and correlation analysis was conducted. RESULTS: Compared with the control group, the levels of serum LRG-1, the expression of LRG-1 protein, collagen I, and fibronectin in kidney in the Ang II group were increased (all P<0.01). After treating with irbesartan, renal damage of hypertensive mice was alleviated, while the levels of LRG-1 in serum and kidney were decreased, and the expression of collagen I and fibronectin was down-regulated (all P<0.01). Correlation analysis showed that the level of serum LRG-1 was positively correlated with urinary protein-creatinine ratio, blood urea nitrogen, and blood creatinine level in hypertensive kidney damage mice. Serum level of LRG-1 was also positively correlated with serum inflammatory factors including TNF-α, IL-1β, and IL-6. CONCLUSIONS Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage.
Animals ; Mice ; Mice, Inbred C57BL ; Fibronectins ; Irbesartan ; Creatinine ; Kidney/physiology* ; Hypertension/complications* ; Angiotensin II ; Collagen Type I

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.

Objective:Jue tone is a kind of sound,using 3-mi as the main tone,and is melodious,profound,makes people feel comfortable and pleasant.This study aimed to explore the probable mechanism of Jue tone to reduce blood pressure (BP) in hypertensive rats with a liver-fire hyperactivity pattern by observing changes in BP as well as physiochemical indexes in plasma.Methods:Sixteen male spontaneous hypertensive rats (SHR) with a liver-fire hyperactivity pattern were randomly divided into a control group and a Jue tone group.The rats in the Jue tone group were treated with Jue tone (55-65 dB,played by the five elements of music rhythm instrument,a kind of physio-therapy regimen music played by Shen Wu) once a day for 4 weeks.The BP levels in each group were measured twice a week,on Monday and Friday.The levels of angiotensin Ⅱ (Ang-Ⅱ),thromboxane B2(TXB2),endothelin-1 (ET-1),calcitonin gene-related peptide (cGRP),norepinephrine (NE),cortisol(CORT),and 5-hydroxytryptamine (5-HT).in plasma were detected by enzyme-linked immunosorbent assay after 4 weeks of intervention.Results:BP and the levels of TXB2 and ET-1 in the plasma of the treatment group were significantly lower than those of the control group,while the level of cGRP was significantly higher.Conclusion:Jue tone can reduce the BP of hypertensive rats with a liver-fire hyperactivity pattern.The mechanism may correlate with a reduction in TXB2 and ET-1 and an increase in cGRP with the reduction of reactive oxygen species (ROS).

Objective To explore the correlation between EBV DNA load and peripheral immune cells (including lymphocyte supsets and natural killer cells) before treatment in patients with NPC, and analyze the influence of circulating immune cell supsets related to EBV on the prognosis of NPC patients. Methods We retrospectively analyzed the general data of 203 NPC patients without distant metastasis at the first treatment, as well as the data of peripheral blood EBV DNA and circulating immune cell supset. The ROC curve analysis was used to determine the cutoff value of each circulating immune cell supset. Kaplan-Meier method was used for survival analysis, and Cox regression model was used for multi-factor prognostic correlation analysis. Results The 3-year OS, PFS, DMFS and LRFS of EBV DNA < 400 copies/ml group and EBV DNA≥400 copies/ml group were 99.2% vs. 90.1% (P=0.001), 96.7% vs. 90.1% (P=0.028), 98.4% vs. 90.1% (P=0.005) and 98.4% vs. 100% (P > 0.05), respectively. EBV DNA is negatively correlated with the ratio of CD19⁺ B cells before treatment (r=-0.138, P=0.040), and there was no significant correlation between EBV DNA and other circulating immune supgroups (P > 0.05). ROC analysis showed that the cut-off value of CD19⁺B cell ratio before treatment related to the 3-year OS was 8.33% (P=0.02). The 3-year OS, PFS, DMFS and LRFS of patients with CD19⁺B cells ratio ≤8.33% and CD19⁺B cells ratio > 8.33% were respectively 90.4% vs. 99.2% (P=0.003), 89.2% vs. 97.5% (P=0.008), 90.4% vs. 98.3% (P=0.008) and 98.8% vs. 99.2% (P > 0.05). However, ROC analysis showed that there was no significant correlation between OS and other peripheral immune cells (including the proportion of CD3⁺T, CD3⁺CD4⁺T, CD3⁺CD8⁺T and CD56⁺NK cells and CD4⁺/CD8⁺ ratio). Multivariate analysis showed that EBV DNA load was an independent prognostic factor of 3-year PFS of NPC patients, and the ratio of CD19⁺B cells was an independent prognostic factor of 3-year PFS, MFS and OS of NPC patients. Conclusion Before treatment, there is a negative correlation between plasma EBV DNA and the proportion of CD19⁺B cells in peripheral blood. Both can be used as the predictors of 3-year OS, PFS and DMFS of NPC patients.

Objective: To observe the changes in nutrition indicators and the effect on chemotherapy complications as well as the safety of enteral nutrition by way of providing enteral nutrition support for children with acute lymphoblastic leukemia (ALL) at the stage of induction chemotherapy. Methods: From November 2016 to September 2017, 60 children with newly diagnosed ALL at the Hematology Oncology Center of Beijing Children′s Hospital were enrolled in this study.They were randomly divided into an experimental group and a control group, 30 cases for each group.The experimental group was given a high-calorie diet, high-quality protein, and high-medium-chain trigly-ceride enteral nutrition on the basis of a conventional low-fat diet, and the duration lasted the whole induction treatment of ALL children; while the control group was given a low-fat diet routinely.By analyzing relevant indicators before induction chemotherapy (D0), chemotherapy day 15 (D15), and after chemotherapy (D33), the changes in nutritional status and the effect on chemotherapy complications in 2 groups were investigated. Results: There was no significant difference in the body mass index (BMI) and the thickness of triceps skinfold between 2 groups before and after chemotherapy (all P>0.05). The upper arm circumference increased after chemotherapy in the experimental group[before treatment: (15.80±2.63) cm, after treatment: (16.27±2.57) cm], while that of the control group decreased slightly[before chemotherapy: (17.19±3.71) cm, after chemotherapy: (17.15±3.64) cm], and the difference between 2 groups was statistically significant (P<0.05). After chemotherapy, the total protein levels in two groups decreased[the experimental group: (64.52±4.85) g/L, the control group: (61.97±4.65) g/L] which was significantly different from that before chemotherapy [the experimental group: (68.17±6.37) g/L, the control group: (68.08±5.14) g/L] (P<0.01). The total protein level of the experimental group after chemotherapy was significant higher than that in the control group (P<0.05). Both albumin levels in 2 groups increased after chemotherapy [(42.45±4.32) g/L in the experimental group and (41.15±3.73) g/L in the control group], and there was a significant difference between 2 groups before chemotherapy [(39.54±3.26) g/L in the experimental group and (40.01±4.37) g/L in the control group] (P<0.05). The level of prealbumin increased after chemotherapy in both groups [(324.57±64.328) mg/L in the experimental group and (293.07±69.09) mg/L in the control group] compared with that before chemotherapy [(121.10±35.13) mg/L in the experimental group and(131.20±52.77) mg/L in the control group]. The change was statistically significant (P<0.01). The albumin level in the experimental group before chemotherapy was lower than that in the control group after chemotherapy, but it was higher than that in the control group after chemotherapy.Protein differences were statistically significant (P<0.05). The reduction rate of elemental iron in the experimental group after chemotherapy was lower than that in the control group, but it was not statistically significant (P>0.05). Elemental zinc was not significantly different compared with the control group.The incidence of neutropenia after chemotherapy in ALL children was higher (37/60 cases, 61.67%). The recovery of neutropenia after chemotherapy in the experimental group was better than that in the control group.After chemotherapy, the severity of anemia in the experimental group was lighter than that in the control group.The amount of blood transfusion required and amount of transfusion per capita were less than those in the control group (54 person-times vs.74 person-times, 2.45 times vs.3.08 times). The total number of transfused blood products was less than that of the control group (78 person-times vs.101 person-times), but none of the findings above were statistically significant (all P>0.05). The degree of hepatic damage in the experimental group decreased after chemotherapy, but there was no significant change in the control group.The initial activated partial thromboplastin time(APTT) prolongation in the trial group was more than that in the control group (5 cases vs.3 cases), and less than the control group (0 case vs.1 case) after chemotherapy.The frequency of fever in the experimental group during chemotherapy was less than that in the control group (6 cases vs.8 cases), and the average time of fever was shorter than that in the control group (2.8 d vs.4.1 d). None of the above findings were statistically significant (all P>0.05). During the course of chemotherapy, 0 pancreatitis occurred in the experimental group, and 1 pancreatitis occurred in the control group.There was no difference in remission rates between 2 groups of chemotherapy for 15 days and chemotherapy for 33 days. Conclusions The nutritional status of children with ALL was reduced after initial induction chemotherapy.Enteral nutrition support was helpful to maintain the nutritional status for children at the initial stage of chemotherapy, high-calorie diet, high-quality protein, and high-medium-chain triglyceride enteral nutrition support improves blood system tolerance to chemotherapy and reduces chemotherapy complications.

Objective: To investigate the value of combination of A²DS² score, procalcitonin (PCT) and C-reactive protein (CRP) predicting stroke-associated pneumonia (SAP) in patients with acute ischemic stroke. Methods: Patients with acute ischemic stroke admitted to the Department of Neurology, Suqian People's Hospital of Nanjing Drum Tower Hospital Group from March 2015 to March 2019 were enrolled retrospectively. Multivariate logistic regression analysis was used to determine the independent correlation of A²DS² scores as well as PCT and CRP levels with SAP. Receiver operating characteristic (ROC) curves were used to assess the individual and combined predictive values of A²DS² scores, PCT and CRP levels for SAP. Results: A total of 332 patients with acute ischemic stroke were enrolled, and 58 of them developed SAP (17.5%). After adjusting for age, smoking, and hyperlipidemia, the A²DS² score (odds ratio [OR] 1.613, 95% confidence interval [CI] 1.092-2.389), PCT (OR 8.047, 95% CI 3.012-16.138) and CRP (OR 1.409, 95% CI 1.064-2.672) were the independent predictors of SAP occurrence. ROC curve analysis showed that the area under the curve of A²DS² score, PCT and CRP alone, and the combination of the three for predicting SAP were 0.811, 0.825, 0.804 and 0.910, respectively. When the three are jointly used to predict SAP, the area under the curve is significantly higher than the individual prediction (all P<0.001). Conclusions The combination of A²DS² score, PCT and CRP can improve the ability to predict SAP.

Objective To investigate the effect of Taurine on the differentiation of neural stem cells(NSCs)in fetal rats with intrauterine growth restriction( IUGR),and to explore the neuroprotective mechanism of Taurine. Methods IUGR fetal rats models were established with low protein diet. NSCs from subventricular zone( SVZ)were isolated and cultured in υitro. The NSCs were divided into 3 groups:normal control group,IUGR group,and IUGR+Taurine group. The cells were examined by adopting immunofluorescence for counting βⅢ-tubulin protein,glial fibril-lary acidic protein(GFAP)and myelin basic protein(MBP)-positive cells. Protein levels of βⅢ-tubulin and GFAP were detected by using Western blot. Results (1)The number of βⅢ-tubulin protein positive cells in normal control group,IUGR group and IUGR+Taurine group were(18. 50 ± 0. 64)%,(15. 61 ± 0. 76)% and(18. 42 ± 0. 82)%, respectively;the number of GFAP positive cells in normal control group,IUGR group and IUGR+Taurine group were (72. 19 ± 0. 82)%,(74. 87 ± 0. 67)% and(71. 68 ± 0. 92)%,respectively;and the differences were statistically sig-nificant(F＝49. 103,44. 643,all P<0. 01). Compared with the normal control group,βⅢ-tubulin protein positive cells in IUGR group decreased significantly(P<0. 01),but GFAP positive cells in IUGR group increased significantly (P<0. 01). Compared with IUGR Group,βⅢ-tubulin protein positive cells in IUGR+Taurine group increased sig-nificantly(P<0. 01),but GFAP positive cells in IUGR+Taurine group decreased significantly(P<0. 01). There was no significant difference between groupⅠand groupⅢ(all P>0. 05).(2)The levels of βⅢ-tubulin protein in nor- mal control group,IUGR group and IUGR+Taurine group were 0. 44 ± 0. 02,0. 33 ± 0. 03 and 0. 42 ± 0. 02,respective-ly;and the levels of GFAP protein in normal control group,IUGR group and IUGR+Taurine group were 1. 13 ± 0. 02, 1. 50 ± 0. 04,1. 21 ± 0. 01,respectively;and the differences were statistically significant(F＝45. 191,234. 525,all P<0. 01). Compared with normal control group,the levels of βⅢ-tubulin protein in IUGR group decreased significantly (P<0. 01),but the levels of GFAP in IUGR group increased significantly(P<0. 01). Compared with IUGR group, the levels of βⅢ-tubulin protein in IUGR+Taurine group increased significantly(P<0. 01),but the levels of GFAP in IUGR+Taurine group decreased significantly(P<0. 01). There was no significant difference between normal control group and IUGR+Taurine group(all P>0. 05). Conclusions Taurine can promote the differentiation of NSCs toward neurons in IUGR fetal rats,and maintain the normal proportion of all differentiated cells.