Comparison of the effectiveness of anchoring needles and coils in localizing multiple nodules in the lung.

BACKGROUND: Recently, a new type of pulmonary nodule positioning needle has been adopted clinically. We aimed to evaluate the efficacy and safety of a new type of localization needles compared with coils for the simultaneous localization of multiple pulmonary nodules guided by computed tomography (CT) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From January 2021 to March 2022, 87 pulmonary nodules from 40 patients were localized using the new localization needle. From January 2020 to December 2020, 68 pulmonary nodules in 31 patients were localized using coils. The relative outcomes were compared. RESULTS: The success rate of pulmonary nodule localization in the needle group was 97.7% while that in the coil group was 98.5%. In the needle group, the time needed to locate the first nodule was significantly shorter than in the coil group (10.9 min vs. 17.2 min, P = 0.001). Moreover, the time needed per patient was also significantly shorter for the needle group compared with the coil group (23.7 min vs. 30 min, P = 0.017). The incidence of pneumothorax in the needle group was 25.0% vs. 12.9% in the coil group (P = 0.204). The rate of pulmonary hemorrhage in the needle group was 40.0% vs. 32.3% in the coil group (P = 0.502). The success rate of VATS wedge resection was 100% in both groups. CONCLUSION: Both disposable pulmonary nodule localization needles and coils are safe and effective for CT-guided localization of multiple pulmonary nodules of the same stage prior to VATS. However, the use of needles is time-saving compared with the use of coils. The coil localization may exhibit better safety than needle localization.

I-125 seeds insertion with TACE for advanced HCC: a meta-analysis of randomized controlled trials.

PURPOSE: To assess the effectiveness of I-125 seeds (IS) insertion with transcatheter arterial chemoembolization (TACE) in treating patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS: An extensive search was conducted for relevant randomized controlled trials (RCTs) from the establishment date of each database to November 2020. RESULTS: A total of nine RCTs were included in this study. Our analysis showed no significant changes in the pooled Δalpha-fetoprotein values (p = .06), incident rates of myelosuppression (p = .46), vomit occurrence (p = .27), and abnormal liver function (p = .42) between the two treatment groups. However, the complete response (p < .00001), total response (p < .00001), and disease control (p < .00001) rates were significantly higher in patients who underwent TACE with IS insertion, as opposed to patients who received TACE alone. Furthermore, patients who underwent TACE with IS insertion experienced markedly longer pooled overall survival (OS) time (p < .0001), with better OS rates at the six-month (p = .0002), one-year (p < .0001), and three-year (p = .0003) follow-ups than patients who received TACE alone. CONCLUSION: TACE with IS insertion can significantly improve clinical response and prolong the survival of advanced HCC patients.

Antifungal resistance-modifying multiplexing action of Momordica charantia protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in Candida albicans.

Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multi-alterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemo-sensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23-40.00 µg/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10 mg/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08-2.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52-55.33% decrease of cytochrome P450 lanosterol 14α-demethylase, glucan 1, 3-ß glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency. LAY SUMMARY: A new platform to modify resistance is fungal growth-dependent gene coregulation. MAP30 and phosphorylated derivatives are candidate resistance-modifying agents. Low-dose stepwise treatment absolutely modifies azole resistance in model fungus.

EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6.

Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy.

Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells.

Nephron progenitor cells surround around the ureteric bud tips (UB) and inductively interact with the UB to originate nephrons, the basic units of renal function. This process is determined by the internal balance between self-renewal and consumption of the nephron progenitor cells, which is depending on the complicated regulation networks. It has been reported that Zeb1 regulates the proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in nephrons generation is not clear, especially in metanephric mesenchyme (MM). Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU assay, flow cytometry assay and wound healing assay, respectively. Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney. Besides, the dual-luciferase assay was conducted to study the molecular relationship between Zeb1 and Six2. We found that knock-down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in MM cells and Zeb1 overexpression contributed to the opposite results. Similarly, Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However, double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells compared with control cells. Nevertheless, double silence of Zeb1 and Six2 repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had an identical pattern in distinct developing phases of embryonic kidney. These results indicated that there may exist a complicated regulation network between Six2 and Zeb1. Together, we demonstrate Zeb1 promotes proliferation and apoptosis and inhibits the migration of MM cells, in association with Six2.

Six2 Is a Coordinator of LiCl-Induced Cell Proliferation and Apoptosis.

The metanephric mesenchyme (MM) cells are a subset of kidney progenitor cells and play an essential role in mesenchymal-epithelial transition (MET), the key step of nephron generation. Six2, a biological marker related to Wnt signaling pathway, promotes the proliferation, inhibits the apoptosis and maintains the un-differentiation of MM cells. Besides, LiCl is an activator of Wnt signaling pathway. However, the role of LiCl in cellular regulation of MM cells remains unclear, and the relationship between LiCl and Six2 in this process is also little known. Here, we performed EdU assay and flow cytometry assay to, respectively, detect the proliferation and apoptosis of MM cells treated with LiCl of increasing dosages. In addition, reverse transcription-PCR (RT-PCR) and Western-blot were conducted to measure the expression of Six2 and some maker genes of Wnt and bone-morphogenetic-protein (BMP) signaling pathway. Furthermore, luciferase assay was also carried out to detect the transcriptional regulation of Six2. Then we found LiCl promoted MM cell proliferation at low-concentration (10, 20, 30, and 40 mM). The expression of Six2 was dose-dependently increased in low-concentration (10, 20, 30, and 40 mM) at both mRNA and protein level. In addition, both of cell proliferation and Six2 expression in MM cells declined when dosage reached high-concentration (50 mM). However, Six2 knock-down converted the proliferation reduction at 50 mM. Furthermore, Six2 deficiency increased the apoptosis of MM cells, compared with negative control cells at relative LiCl concentration. However, the abnormal rise of apoptosis at 30 mM of LiCl concentration implies that it might be the reduction of GSK3ß that increased cell apoptosis. Together, these demonstrate that LiCl can induce the proliferation and apoptosis of MM cells coordinating with Six2.

MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e.

Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3'UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo. Moreover, Western blot results demonstrated that miR542-3p may promote EMT in the NRK52e cell line. In addition, we confirmed that BMP7, which played a crucial role in anti-kidney fibrosis and suppressed the progression of EMT, was a target of miR542-3p through Dual-Luciferase reporter assay, as did Western blot analysis. The effects of miR542-3p on regulating EMT could also be suppressed by transiently overexpressing BMP7 in NRK52e cells. Taken together, miR542-3p may be a critical mediator of the induction of EMT via directly targeting BMP7.

Predictive value for mortality of left ventricular wall thickness in dilated cardiomyopathy.

AIMS: The purpose of this study was to explore the predictive value of wall thickness measured by cardiac magnetic resonance (CMR) for all-cause mortality in dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: DCM patients who underwent CMR and completed the regular follow-up were included in this study. The left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic volume (LVEDV), left ventricular posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular ejection fraction, and left ventricular mass (LVM) were measured by CMR. The presence and extent of late gadolinium enhancement (LGE) were also assessed. The relative posterior wall thickness (RWTPW ) and relative interventricular septum wall thickness (RWTIVS ) were defined by the following equations: RWTPW  = (2 × PWT)/LVDd, and RWTIVS  = (2 × IVST)/LVDd. All patients received regular telephone and outpatient follow-up. The primary endpoint was all-cause mortality. A total of 161 patients were enrolled in this study, including 126 (78.3%) males. The mean age was 52.3 ± 13.6 years. During the median follow-up of 47 months (interquartile range 32-57 months), 41 (24.8%) patients died. Compared with the non-death group, LVDd (75.2 ± 11.9 vs. 70.5 ± 8.8 mm; P = 0.025) was greater in the death group, while PWT [5.2 mm (3.7-6.8) vs. 6.9 mm (5.3-8.6); P < 0.001], IVST [8.2 mm (6.5-9.5) vs. 9.3 mm (7.4-10.5); P = 0.005], RWTPW [0.15 (0.11-0.19) vs. 0.20 (0.15-0.25); P < 0.001], RWTIVS [0.22 (0.17-0.26) vs. 0.26 (0.22-0.31); P < 0.001], and LVM/LVEDV ratio (0.5 ± 0.2 vs. 0.7 ± 0.2 g/mL; P < 0.001) were lower. The presence of LGE [LGE(+)] was more frequent in the death group (75.6% vs. 58.3%; P = 0.048). However, the LGE extent was not significantly different between the two groups [4 (1-7) vs. 2 (0-6); P = 0.096]. Multivariate Cox regression analysis showed that PWT [hazard ratio (HR) 0.086, 95% confidence interval (CI) 0.665-0.976; P < 0.05] and RWTPW (HR 0.001, 95% CI 0.000-0.502; P < 0.05) were independent predictors of all-cause death. In contrast, IVST, RWTIVS , and the presence of LGE were not clearly associated with death. CONCLUSIONS: PWT measured by CMR is an independent predictor of all-cause mortality in DCM patients. However, there was no significant correlation between septum wall thickness and mortality.

BMP7 plays a critical role in TMEM100-inhibited cell proliferation and apoptosis in mouse metanephric mesenchymal cells in vitro.

Kidney mainly arises from the induction of metanephric mesenchymal cells (MM cells) and the ureteric bud (UB). Transmembrane protein-100 (Tmem100) consists of two transmembrane regions with strong temporal and spatial expression characteristics during renal development. However, the function of Tmem100 in mouse embryonic kidney-derived cells remained unclear. We provided qPCR to verify the relationship between Tmem100 and the BMP signal pathway. To clarify the role of Tmem100 in cell proliferation and apoptosis, we carry out EdU incorporation, annexin V- fluorescein isothiocyanate (FITC) apoptosis assay. Here, we find that the knockdown of Tmem100 increases the proliferation and apoptosis of mouse embryonic kidney-derived cells, and this promotion can be inhibited by knockdown of BMP7 at the same time; these results suggest that BMP7 plays a crucial role in Tmem100-regulated cell proliferation and apoptosis. qRT-PCR results further demonstrate that the deficiency of Tmem100 leads to BMP7 upregulation and overexpression could get opposite results. In BMP7-depleted MK3 cells, Tmem100 is highly upregulated and BMPR-II is downregulated. And in BMP7-overexpressed MK3 cells, the expression of Tmem100 is decreased. In BMPR-II-depleted MK3 cells, Tmem100 is downregulated and BMP7 expression remains still. These findings indicate that both BMP7 and BMPR-II can regulate Tmem100 and vice versa, and BMPR-II expression is regulated by BMP7. However, BMP7 has no association with BMPR-II in MK3 cells. Our data demonstrated the significant role of BMP7 in Tmem100-regulated cell proliferation and apoptosis and revealed the complicated regulation network among Tmem100, BMP7, and BMPR-II in mouse embryonic kidney-derived cells.

Six2 is involved in GATA1-mediated cell apoptosis in mouse embryonic kidney-derived cell lines.

Six2 (Sine oculis homeobox 2), a homeodomain transcription factor, plays a crucial role in the regulation of mammalian nephrogenesis. It is also implicated in numerous biological functions, such as cell proliferation, apoptosis, and migration. However, the underlying regulatory mechanisms of Six2 remain largely unknown. In this study, we predicted that CRX, GATA1, HOXD8, and POU2F2 might target, binding to the promoter region of Six2 (~2000 bp) by bioinformatics analysis. Among the four genes, the predicted binding sequence of GATA1 is most highly conserved across species. Luciferase assays demonstrated that knockdown of GATA1 decreased the activity of Six2 promoter and qPCR result of Six2 expression was in consistent with this in 293T cells. Mutation of GATA1 binding sites of mSix2 promoter led to obvious decrease of the mSix2 promoter activity. Furthermore, knockdown of GATA1 decreased Six2 expression in mk3 cells and increased cell apoptosis of mk3 and mk4 compared with corresponding control cells, but this up-regulation can be rescued by Six2 overexpression. Our findings indicated that GATA1 may be a potential regulator of Six2-maintained population of nephron progenitor cells.

Proliferation of metanephric mesenchymal cells is inhibited by miR-743a-mediated WT1 suppression in vitro.

To seek out the potential microRNAs (miRNAs) that target Wilms' tumor suppressor 1 (WT1), a transcription factor required for progenitor proliferation as well as normal development of the kidney, and to clarify the effects of the miRNAs on WT1, the 3'-untranslated region (3'­UTR) of WT1 was initially analyzed and miR­743a, a seldom­reported miRNA, was identified. In the present paper, luciferase reporter assays were performed to confirm that miR­743a is able to directly target the 3'­UTR of WT1. Subsequently, reverse transcription­quantitative polymerase chain reaction, combined with western blotting analyses, were performed, and the results revealed a significant inhibition of WT1 at the mRNA and the protein levels. Furthermore, a 5­ethynyl­2'­deoxyuridine (EdU) cell proliferation assay, coupled with a WT1 rescue strategy, demonstrated that miR­743a inhibited the proliferation of metanephric mesenchymal (MM) cells, in part by targeting WT1. In conclusion, by targeting WT1, miR­743a suppresses the proliferation of MM cells in vitro, and probably possesses vital functions in kidney development and kidney­associated diseases.

The expression patterns of Tetratricopeptide repeat domain 36 (Ttc36).

Tetratricopeptide repeat domain 36 (Ttc36), whose coding protein belongs to tetratricopeptide repeat (TPR) motif family, has not been studied extensively. We for the first time showed that Ttc36 is evolutionarily conserved across mammals by bioinformatics. Rabbit anti-mouse Ttc36 polyclonal antibody was generated by injecting synthetic full-length peptides through "antigen intersection" strategy. Subsequently, we characterized Ttc36 expression profile in mouse, showing its expression in liver and kidney both from embryonic day 15.5 (E15.5) until adult, as well as in testis. Immunofluorescence staining showed that Ttc36 is diffusely expressed in liver, however, specifically in kidney cortex. Thus, we further compare Ttc36 with proximal tubules (PT) marker Lotus Tetragonolobus Lectin (LTL) and distal tubules (DT) marker Calbindin-D28k respectively by double immunofluorescence staining. Results showed the co-localization of Ttc36 with LTL rather than Calbindin-D28k. Collectively, on the basis of the expression pattern, Ttc36 is specifically expressed in proximal distal tubules.

The incidence and risk of osteoporosis in patients with anxiety disorder: A Population-based retrospective cohort study.

The purpose of this study was to investigate the relationship between anxiety disorder (AD) and the subsequent development of osteoporosis.We conducted a population-based retrospective cohort analysis according to the data in the Longitudinal Health Insurance Database 2000 of Taiwan. We included 7098 patients in both the AD and no-anxiety cohort who were matched according to age and sex between January 1, 2000, and December 31, 2013. The incidence rate and the risk ratios (RRs) of subsequent new-onset osteoporosis were calculated for both cohorts. We used Cox proportional hazards models to assess the effect of AD. The Kaplan-Meier method was applied to estimate the cumulative osteoporosis incidence curves.The AD cohort consisted of 7098 patients, and the comparison cohort comprised the same matched control patients without anxiety. The risk of osteoporosis was higher in the AD cohort than in the comparison cohort. In addition, the incidence of newly diagnosed osteoporosis remained significantly increased in all of the stratified follow-up durations (0-1, 1-5, 5-10, ≥10years). Patients with AD were 1.79 times more likely to get osteoporosis than those without AD. We also observed a significant increase in osteoporotic risk in AD patients who are comorbid with hypertension, diabetes mellitus, and chronic liver disease.The incidence of osteoporosis in Taiwan is associated with an a priori AD history. The risk ratios are the highest for osteoporosis within 1 year of AD diagnosis, but the risk remains statistically significant for >1 year. Clinicians should pay particular attention to osteoporotic comorbidities in AD patients.