OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities. Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed. Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system. Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

Objective To conduct a scoping review of studies on the use of virtual reality(VR)in cancer-related cognitive impairment(CRCI),and to generalize and summarize the current state of the art of VR use in CRCI.Methods The computerized retrieval of PubMed,Embase,Web of Science,the Cochrane Library,WanFang Data,CNKI and VIP databases was carried out.Studies were collected from the database establishment to July 2023.3 researchers independently screened the literature,extracted data,and evaluated the risk of bias in the included studies.Results A total of 9 studies were included.VR was used for CRCI assessment and intervention.The assessment included visual and auditory memory,executive function and verbal fluency.The intervention content involved common cognitive impairment dimensions of CRCI,including memory,executive ability,attention,information processing speed and language fluency.The intervention frequency ranged from 3 to 5 times/week,15 to 60 min/time,and the duration was 2 to 8 weeks.The intervention frequency and intensity were dynamically adjusted based on the patient performance,game type and complexity.VR has shown good validity and benefits in CRCI assessments and interventions,while improving patients'sleep quality and ability to perform daily living,with higher patient acceptance and no VR related adverse events being reported,but its role in improving mental health remains controversial.Conclusion VR shows good validity and benefits in CRCI assessment and intervention,and has good safety and high acceptance.In the future,it is still necessary to conduct large-sample,randomized controlled studies,attach importance to the role of patient needs in the formulation of VR cognitive intervention programs,and increase CRCI-related objective indicators to further verify the effect of VR intervention on CRCI.At the same time,longitudinal evaluation and follow-up programs may be considered to determine progressive changes in CRCI from VR interventions.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals. METHODS: Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated. RESULTS: SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. CONCLUSION s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
Humans ; COVID-19 Vaccines/therapeutic use* ; COVID-19 ; SARS-CoV-2 ; Killer Cells, Natural ; HIV Infections ; Antibodies, Viral

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective:To compare the effects of rosuvastatin and atorvastatin on coronary artery bypass grafting (CABG) on the incidence of acute kidney injury (AKI), and assess the independent risk factors of AKI.Methods:We retrospectively collected 550 patients aged 18 years or older who underwent CABG from May 2014 to May 2020. They were divided into the rosuvastatin group ( n=322), atorvastatin group ( n=125) and non statins group ( n=103) according to whether rosuvastatin or atorvastatin was routinely used before operation. Demographic data, clinical data before and after CABG and laboratory results were collected. Blood urea nitrogen (BUN), serum creatinine (Scr), creatinine clearance rate (Ccr) and incidence of postoperative AKI were compared among the three groups. Univariate analysis and binary logistic regression analysis were used to investigate the effect of statins on AKI in patients undergoing CABG. Results:Compared with preoperation, BUN showed no significant change ( P>0.05), while Scr was increased and Ccr was decreased significantly (both P<0.01); BUN in the rosuvastatin group was decreased significantly ( P<0.01), whereas Scr and Ccr had no significant change ( P>0.05); Scr in the atorvastatin group was increased significantly ( P<0.01), but there was no significant difference in BUN and Ccr ( P>0.05). BUN and Scr in the non statins group were increased significantly (both P<0.01), while Ccr was decreased significantly ( P<0.01). After operation, BUN and Scr in the rosuvastatin group and atorvastatin group were significantly lower than those in the non statins group (all P<0.01); Ccr was significantly higher than that in the non statins group ( P<0.01). BUN and Scr were not significantly different between the rosuvastatin and atorvastatin groups ( P>0.05), but Ccr was significantly higher than that in the atorvastatin group ( P< 0.05). There were significant differences in BUN, Scr and Ccr among the three groups ( χ2=48.925, 22.677 and 34.426, all P<0.01). The incidence of AKI among 550 patients was 15.1% (83/550), of which 9.6% (31/322) in the rosuvastatin group, 16.0% (20/125) in the atorvastatin group and 31.1% (32/103) in the non statins group. The incidence of AKI in the rosuvastatin and atorvastatin groups was significantly lower than that in the non statins group ( χ2=28.412, 7.282, P<0.01). Multivariate regression analysis showed that hypertension ( OR=3.555, 95% CI: 1.959-6.451, P<0.01), NHYAⅢ/Ⅳ ( OR=2.438, 95% CI: 1.187-5.008, P=0.015), and increased serum creatinine level ( OR=1.018, 95% CI: 1.003-1.032, P=0.016), and intraoperative cardiopulmonary bypass ( OR=2.936, 95% CI: 1.454-5.927, P=0.003) were independent risk factors for AKI after CABG, while preoperative conventional statin therapy ( OR=0.490, 95% CI: 0.247-0.974, P=0.042) and increased serum albumin level ( OR=0.920, 95% CI: 0.856-0.990, P=0.026) were protective factors for AKI after CABG. Conclusions:The incidence of AKI after CABG is common. Rosuvastatin or atorvastatin and increased preoperative serum albumin level can protect renal function and reduce the incidence of AKI, which are the protective factors of AKI after CABG. The hypertension, NHYAⅢ/Ⅳ, increased preoperative serum creatinine level and cardiopulmonary bypass are the independent risk factors of AKI after CABG.