A case report and literature review on nephrogenic alveolar soft part sarcoma: clinicopathological manifestations and genetic features.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare kind of malignant soft tissue tumor with undefined differentiation, of which the incidence rate accounts for only 0.5-1.0% among all kinds of soft tissue tumors. An even rarer ASPS occurs in kidney. CASE PRESENTATION: Here we reported a case of a 7-year-old girl diagnosed with nephrogenic ASPS, regarding the analyses of the incidence, clinical manifestation, pathology and genetic diagnosis, in order to deepen the recognition of the disease. CONCLUSIONS: ASPS is very rare, and tends to occur to young patients. It is very significant to precisely diagnose ASPS at an early stage, which will be the key point for the following treatment choices and prognosis.

DJ-1 inhibits autophagy activity of prostate cancer cells by repressing JNK-Bcl2-Beclin1 signaling.

The regulation of DJ-1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ-1 could alter autophagy and regulate Beclin1-involved autophagy response through JNK-dependent pathway. JNK is known to mediate autophagy through Bcl2-Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ-1-modulated PCa cells. The current studies showed that DJ-1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ-1 knockdown exerted the opposite effect. Moreover, DJ-1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3-MA. In addition, DJ-1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ-1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ-1-overexpressed LNCaP while increasing LC3 transformation and LC3-puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin-1). In contrast, when DJ-1 was silenced, the death of LNCaP, LC3 transformation, and LC3-puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ-1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK-Bcl2-Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ-1 in the development of PCa.

Clinical and molecular spectrum of CHOPS syndrome.

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development.

[Molecular diagnosis of children with unexplained intellectual disability/ developmental delay by array-CGH].

OBJECTIVE: To analyze the potential pathogenic genomic imbalance in children with unexplained intellectual disability (ID) and/or developmental delay (DD) and its association with phenotypes, and to investigate the value of array-based comparative genomic hybridization (array-CGH) in clinical molecular genetic diagnosis. METHODS: The whole genome of 16 children with ID/DD was scanned by the array-CGH for detection of genomic copy number variations (CNVs), and the revealed genomic imbalance was confirmed by multiplex ligation-dependent probe amplification. RESULTS: G-band karyotyping of peripheral blood cells showed no abnormalities in the 16 children. The results of the array-CGH revealed that 6 (38%) of the 16 patients had genomic CNVs, and 3 cases of CNVs were normal polymorphic changes; 1 CNV was a microdeletion of 4p16.3, which was the critical region for Wolf-Hirschhorn syndrome, and 1 CNV was a microdeletion of 7q11.23, which was the critical region for Williams-Beuren syndrome. Moreover, a CNV was identified with two duplications at 2q22.2 and 15q21.3 in a boy, which proved to have a clinical significance due to its association with ID, brain DD, unusual facies, cryptorchidism, irregular dentition, etc. CONCLUSIONS: Array-CGH allows for the etiological diagnosis in some of the children with unexplained ID/DD. As a high-throughput and rapid tool, it has a great clinical significance in the etiological diagnosis of ID/DD.

Cardiac Arrhythmia Risk after Anti-Cancer Drug Exposure and Related Disease Molecular Imaging Outlook: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.

BACKGROUND: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. METHODS: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case-control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. RESULTS: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines' use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62-2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18-3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100-25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80-2105.83]) by network meta-analysis. CONCLUSIONS: Our findings show a significant association between anthracyclines' use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs.

Enhanced TfR1 Recognition of Myocardial Injury after Acute Myocardial Infarction with Cardiac Fibrosis via Pre-Degrading Excess Fibrotic Collagen.

The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents' metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.

Asymptomatic Rosai-Dorfman-Destombes disease presenting as isolated bilateral perinephric infiltration: a case report and review of the literature.

Background: Rosai-Dorfman-Destombes disease (RDD) is a rare histioproliferative disease with unknown etiology. It commonly occurs in lymph nodes and can affect extra-nodal tissues and organs. Renal RDD is extremely rare, only a few cases have been reported, and its clinical symptoms and imaging findings are non-specific. To date, no literature has summarized its imaging manifestations in a large number of cases. Due to the involvement of different tissues and organs, there is no standard treatment for RDD. It has been reported that RDD patients with kidney involvement have a poor prognosis. Thus, understanding of renal RDD need to be extended. Case Description: We present a rare case of renal RDD in an asymptomatic 67-year-old male. The results of an ultrasound examination indicated that both kidneys were surrounded by hypoechoic soft tissue lesions, and there was a huge mass in the left kidney, which had a clear boundary with the renal capsule. The results of contrast-enhanced ultrasound (CEUS) showed hypo-enhancement in the bilateral perinephric lesions and mass. However, the computed tomography urography (CTU) findings revealed no obvious enhancement. The patient then underwent a series of laboratory tests, but no relevant information was found. To make a clear diagnosis, the urologist then removed the left perirenal mass and some perirenal tissues, and the patient was finally pathologically diagnosed with extra-nodal RDD. The patient remains asymptomatic, and no treatment has been administered to date. Conclusions: This case may be the first reported case in which CEUS was performed and the second reported case of asymptomatic renal RDD. Based on the previous literature reports, we found that some specific characteristics of renal RDD include bilateral perirenal lesions with a "hairy kidney" appearance. CEUS and/or CTU can be used to help differentiate a solitary mass of RDD from common tumors, to avoid misdiagnosis leading to unnecessary nephrectomy.

Association between weight change and the predicted 10-year risk for atherosclerosis cardiovascular disease among U.S. older adults: data from National Health and Nutrition Examination Survey 1999-2018.

Background: It remains controversial regarding the association between weight change and cardiovascular disease risk in older adults (aged ≥60 years). This study aimed to evaluate the association between weight change and the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risks in older adults. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES). Older adults aged 60-79 years who were free of self-reported ASCVD at the time of the NHANES interview were included. Data were collected from January 1999 to December 2018 and analyzed in March 2022. We focused on the associations between weight change and the 10-year ASCVD risks with the percentage change in weight during short-term (1 year) and long-term (10 years), which categorized as moderate to high weight loss (≥10%), small weight loss (5.1-9.9%), stable weight (±5%), small weight gain (5.1-9.9%), and moderate to high weight gain (≥10%). Results: The number of participants was 1,867 (mean age 67.49 years; 42.10% female) for the long-term interval (10 years) in our analysis, and 1894 for the short-term interval (1 years). We only observed an inverse association between long-term weight loss and the 10-year ASCVD risk in fully adjusted model (loss ≥ 10%: ß = 2.52, 95%CI = 0.98, 4.05; loss 5.1% ~ 9.9%: ß = 2.99, 95% CI = 1.30, 4.68), but all intervals of weight gain ≥5% were not significant associated with higher risk than stable weight. However, in the subgroup analyses, the association between long-term weight loss and the 10-year ASCVD risk was not significant in old-old (aged 75-79), obesity (BMI ≥ 35 kg/m2), intentional weight loss, moderate physical activity and diabetics. Conclusion: Older adults (aged 60-79 years) with weight loss >5% over the past 10 years have excess predicted 10-year ASCVD risk. Our study supports the benefits of stable weight in promoting cardiovascular health in older adults.

The NLRP3 inflammasome is involved in resident intruder paradigm-induced aggressive behaviors in mice.

Background: Aggressive behaviors are one of the most important negative behaviors that seriously endangers human health. Also, the central para-inflammation of microglia triggered by stress can affect neurological function, plasticity, and behavior. NLRP3 integrates stress-related signals and is a key driver of this neural para-inflammation. However, it is unclear whether the NLRP3 inflammasome is implicated in the development of aggressive behaviors. Methods: First, aggressive behavior model mice were established using the resident intruder paradigm. Then, aggressive behaviors were determined with open-field tests (OFT), elevated plus-maze (EPM), and aggressive behavior tests (AT). Moreover, the expression of P2X7R and NLRP3 inflammasome complexes were assessed by immunofluorescence and Western blot. The levels of NLRP3 and inflammatory cytokines were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. Finally, nerve plasticity damage was observed by immunofluorescence, transmission electron microscope, and BrdU staining. Results: Overall, the resident intruder paradigm induced aggressive behaviors, activated the hippocampal P2X7R and NLRP3 inflammasome, and promoted the release of proinflammatory cytokines IL-1ß in mice. Moreover, NLRP3 knockdown, administration of P2X7R antagonist (A804598), and IL-1ß blocker (IL-1Ra) prevented NLRP3 inflammasome-driven inflammatory responses and ameliorated resident intruder paradigm-induced aggressive behaviors. Also, the resident intruder paradigm promoted the activation of mouse microglia, damaging synapses in the hippocampus, and suppressing hippocampal regeneration in mice. Besides, NLRP3 knockdown, administration of A804598, and IL-1Ra inhibited the activation of microglia, improved synaptic damage, and restored hippocampal regeneration. Conclusion: The NLRP3 inflammasome-driven inflammatory response contributed to resident intruder paradigm-induced aggressive behavior, which might be related to neuroplasticity. Therefore, the NLRP3 inflammasome can be a potential target to treat aggressive behavior-related mental illnesses.

[Preventive effect of exogenous hydrogen sulfide on hepatic fibrosis in rats].

OBJECTIVE: To determine the effect of exogenous hydrogen sulfide on experimental hepatic fibrosis in rats and its mechanism. METHODS: Wistar male rats were randomly divided into three groups: a normal control group (n=8), a model group (n=8), and a hydrogen sulfide prevention group (n=8). The rat model of hepatic fibrosis was reduced by intraperitoneal injection of carbon tetrachloride (CCl4). The prevention group, in addition to intraperitoneal injection of 40% CCl4, was intraperitoneally administered H2S once a day until 8th week. After the experiment, the liver function and liver fibrosis were assayed. Liver tissue samples were used for histopathological changes. The expression of TGF-ß1 in liver tissue was detected by RT-PCR and Western blot. RESULTS: Compared with the model group, the levels of ALT, AST, HA, LN, and PC III in the sulfide group were significantly reduced (P<0.01 or P<0.05), ALB content was increased (P<0.05) in the serum, TGF-ß1 expression was obviously reduced, and the degree of liver fibrosis was improved (P<0.05). CONCLUSION: Exogenous hydrogen sulfide can effectively inhibit the development of hepatic fibrosis, reduce the expression of TGF-ß1, and decrease the the sediment of extracellular matrix in the liver tissues.

Exposure to various ambient air pollutants increases the risk of venous thromboembolism: A cohort study in UK Biobank.

Epidemiological evidence for the association between air pollutants exposure and venous thromboembolism (VTE) remains controversial. In this study, a total of 389,659 participants from the UK Biobank who were free of VTE in 2010 were included, and the annual mean concentrations of air pollutants near where participants lived were collected. During a median follow-up period of 8.25 years, 4986 VTEs were determined from the hospital admission records. The Cox proportional hazard model was used to examine the association between air pollutants and VTE. We firstly investigated the associations between air pollutants concentration and VTE and found only NO2 and NO increased VTE risk (P < 0.05). We further calculated the product of air pollutant concentrations and outdoor time to measure personal daily cumulative exposure and found that the hazard rates (HRs) of VTE for a 50-µg/m3∗day increase in daily cumulative exposure to PM10, PM2.5, PM2.5-10, NO, and NO2 were 1.08 (1.05-1.12), 1.16 (1.09-1.24), 1.23 (1.11-1.37), 1.04 (1.01-1.06), and 1.05 (1.03-1.08), respectively. To measure joint exposure to various air pollutants and its effect on VTE, we created a weighted air pollutants exposure score (APES) and found a dose-response relationship between APES and VTE risk (P < 0.001 for trend). Compared with participants in the lowest quintile of APES, the HRs of VTE were 1.19 (1.08-1.30) for those within the highest quintile groups. Furthermore, we also found the effect of air pollutants on VTE was statistically significant only in individuals with low-middle VTE genetic risk score (GRS) (P < 0.05), but not in the high VTE GRS groups (P > 0.05). Our findings suggest that exposure to various air pollutants including PM2.5, PM2.5-10, PM10, NO, and NO2, either individually or jointly, were associated with an increased risk of VTE in a dose-response pattern. Our study highlights the importance of a comprehensive assessment of various air pollutants in VTE prevention.

Isolated Diastolic Hypertension and Risk of Cardiovascular Events: A Systematic Review and Meta-Analysis of Cohort Studies With 489,814 Participants.

Background: The association between isolated diastolic hypertension (IDH) and cardiovascular events has been inconsistently reported. This meta-analysis of cohort studies was designed to investigate the effect of the 2018 European Society of Cardiology (ESC) definition of IDH on the risk of composite cardiovascular events, cardiovascular mortality, all-cause mortality, and all strokes including ischemic stroke (IS) and hemorrhagic stroke (HS). Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 6, 2021. Cohort studies that investigated the association between IDH and cardiovascular events risk, compared to normotension, were included. Pooled hazard ratios (HRs) and 95% CIs were calculated using a random-effects models and heterogeneity was evaluated using Q-test and I 2 statistic. The robustness of the associations was identified using sensitivity analysis. The methodological quality of the studies was assessed using the Newcastle-Ottawa scale. Publication bias was assessed using funnel plot, trim-and-fill method, Begg's test, and Egger's test. Results: A total of 15 cohort studies (13 articles) including 489,814 participants were included in this meta-analysis. The follow-up period ranged from 4.3 to 29 years. IDH was significantly associated with an increased risk of composite cardiovascular events (HR 1.28, 95% CI: 1.07-1.52, p = 0.006), cardiovascular mortality (HR 1.45, 95% CI: 1.07-1.95, p = 0.015), all strokes (HR 1.44, 95% CI: 1.04-2.01, p = 0.03), and HS (HR 1.64, 95% CI: 1.18-2.29, p = 0.164), but not associated with all-cause mortality (HR 1.20, 95% CI: 0.97-1.47, p = 0.087) and IS (HR 1.56, 95% CI: 0.87-2.81, p = 0.137). Subgroup analysis further indicated that IDH in the younger patients (mean age ≤ 55 years) and from Asia were significantly associated with an increased risk of composite cardiovascular events, while the elderly patients (mean age ≥ 55 years), Americans, and Europeans were not significantly associated with an increased risk of composite cardiovascular events. Conclusion: This meta-analysis provides evidence that IDH defined using the 2018 ESC criterion is significantly associated with an increased risk of composite cardiovascular events, cardiovascular mortality, all strokes and HS, but not significantly associated with all-cause death and IS. These findings also emphasize the importance for patients with IDH to have their blood pressure within normal, especially in the young adults and Asians. Trial Registration: PROSPERO, Identifier: CRD42021254108.

Long non-coding RNA SAP30L-AS1 promotes prostate cancer growth through repressing SAP30L.

Accumulating evidences have demonstrated the importance of long non-coding RNAs (lncRNAs) in initiation and progression of various cancers, including prostate cancer. LncRNA SAP30L-AS1 is previously identified in the plasma of prostate cancer patients. In this study, we further investigated the expression of SAP30L-AS1 in prostate cancer tissues and cell lines. Moreover, we explored the biological roles and mechanisms of action of SAP30L-AS1 in prostate cancer. The expression of SAP30L-AS1 is found to be increased in prostate cancer tissues and cell lines compared with adjacent noncancerous tissues and normal prostate epithelial cell line, respectively. Increased expression of SAP30L-AS1 is associated with greater Gleason score, advanced pathological T stage, and poor over survival of prostate cancer patients. Functional assays demonstrated that ectopic expression of SAP30L-AS1 promotes prostate cancer proliferation and inhibits prostate cancer apoptosis. SAP30L-AS1 knockdown represses prostate cancer proliferation and induces prostate cancer apoptosis. Furthermore, SAP30L-AS1 knockdown represses prostate cancer xenograft growth in vivo. Mechanistic investigation revealed that SAP30L-AS1 physically binds to the promoter of SAP30L and represses SAP30L expression. The expression of SAP30L is negatively associated with that of SAP30L-AS1 in prostate cancer tissues. Rescue assays demonstrated that overexpression of SAP30L attenuated the roles of SAP30L-AS1 in promoting prostate cancer proliferation and inhibiting prostate cancer apoptosis. In conclusion, SAP30L-AS1 is upregulated and has oncogenic roles in prostate cancer via repressing SAP30L. Our data suggest that SAP30L-AS1 may be a promising prognostic biomarker and therapeutic target for prostate cancer.