The circular RNA circHMGB2 drives immunosuppression and anti-PD-1 resistance in lung adenocarcinomas and squamous cell carcinomas via the miR-181a-5p/CARM1 axis.

BACKGROUND: Previous studies have confirmed the oncogenic role of HMGB2 in various cancers, but the biological functions of HMGB2-derived circRNAs remain unknown. Thus, we intended to investigate the potential role of HMGB2-derived circRNAs in lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). METHODS: The expression profiles of HMGB2-derived circRNAs in LUAD and LUSC tissues and matched normal tissues were assessed using qRT-PCR. The role of circHMGB2 in the progression of the LUAD and LUSC was determined in vitro by Transwell, CCK-8, flow cytometry and immunohistochemistry assays, as well as in vivo in an immunocompetent mouse model and a humanized mouse model. In addition, in vivo circRNA precipitation assays, luciferase reporter assays and RNA pulldown assays were performed to explore the underlying mechanism by which circHMGB2 promotes anti-PD-1 resistance in the LUAD and LUSC. RESULTS: The expression of circHMGB2 (hsa_circ_0071452) was significantly upregulated in NSCLC tissues, and survival analysis identified circHMGB2 as an independent indicator of poor prognosis in the LUAD and LUSC patients. We found that circHMGB2 exerted a mild effect on the proliferation of the LUAD and LUSC cells, but circHMGB2 substantially reshaped the tumor microenvironment by contributing to the exhaustion of antitumor immunity in an immunocompetent mouse model and a humanized mouse model. Mechanistically, circHMGB2 relieves the inhibition of downstream CARM1 by sponging miR-181a-5p, thus inactivating the type 1 interferon response in the LUAD and LUSC. Moreover, we found that the upregulation of circHMGB2 expression decreased the efficacy of anti-PD-1 therapy, and we revealed that the combination of the CARM1 inhibitor EZM2302 and an anti-PD-1 antibody exerted promising synergistic effects in a preclinical model. CONCLUSION: circHMGB2 overexpression promotes the LUAD and LUSC progression mainly by reshaping the tumor microenvironment and regulating anti-PD-1 resistance in the LUAD and LUSC patients. This study provides a new strategy for the LUAD and LUSC treatment.

Minimally Invasive Myxoma Resection: A Single-Center 5 Years' Experience.

BACKGROUND: There is an increasing demand for minimally invasive myxoma resection. This study aimed to investigate the safety and feasibility of minimally invasive myxoma resection. METHODS: In this retrospective study, we collected information from 95 patients who underwent myxoma resection between January 2016 and December 2020. Based on the operative approach, the patients were divided into the minimally invasive myxoma resection (Mini-MR) group (N = 30) and the sternotomy myxoma resection (SMR) group (N = 65). Intraoperative and postoperative data were compared between the two groups. RESULTS: The postoperative ventilator-assisted time, CSICU time, and postoperative hospital stay were shorter in the Mini-MR group than in the SMR (13.05 ± 4.98 vs. 17.07 ± 9.52 h; 1.73 ± 0.29 vs. 2.27 ± 1.53 d; 6.20 ± 1.50 vs. 9.48 ± 3.37 d, respectively), and the difference was statistically significant (P < 0.05). Mini-MR had lower postoperative drainage and blood transfusion rate in the first 24 h compared with SMR (38.93 ± 69.62 vs. 178.25 ± 153.06 ml; 26.6% vs. 63.1%), and the differences were statistically significant (P < 0.05). CONCLUSION: Mini-MR has the advantages of less CSICU stay time, less ventilator time, less postoperative drainage in the first 24h, less blood transfusion, fewer postoperative hospital stays, and faster recovery. Mini-MR is a safe and feasible surgical procedure for myxoma resection.

Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC.

BACKGROUND: CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. METHODS: The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. RESULTS: The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. CONCLUSIONS: Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.

ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation.

BACKGROUND: Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. METHODS: Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. RESULTS: We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. CONCLUSION: Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.

Modified Distal Aortic Arch Occlusion During Aortic Arch Replacement.

BACKGROUND: Circulatory arrest has been identified as an independent risk factor related to postoperative mortality in patients with Stanford type A aortic dissection. This study described a modified technique for distal aortic arch occlusion that markedly shortened the circulatory arrest time. The early results are encouraging. METHODS: From May 2016 to September 2018, 51 patients with Stanford type A aortic dissection underwent the modified procedure for aortic arch replacement. All operations were performed via transitory circulatory arrest by clamping the distal aorta between the left common carotid artery and the left subclavian artery. The in-hospital and follow-up data of the treated patients were investigated. RESULTS: Successful repair of the involved vasculature was achieved in all patients. One (1) patient died due to postoperative aspiration and infection, and three patients required continuous renal replacement therapy due to poor preoperative renal function. The remaining patients were successfully discharged. The median average circulatory arrest time was 5.0 (3.0-6.0) minutes. No cases of tracheotomy, delayed closure, secondary thoracotomy, or other complications occurred. During the follow-up period of 2.4-18.6 months, the implanted grafts and stented elephant trunks were all fully open and not kinked. CONCLUSIONS: A modified distal aortic arch occlusion can considerably shorten the duration of circulatory arrest. Current experience suggests that this approach can serve as a feasible alternative for patients during aortic arch replacement because of its simplicity and satisfactory clinical effects.

CircRNA fibroblast growth factor receptor 3 promotes tumor progression in non-small cell lung cancer by regulating Galectin-1-AKT/ERK1/2 signaling.

The dysregulation of circular RNA (circRNA) expression is involved in the progression of several cancers, including non-small cell lung cancer (NSCLC). However, the role and underlying molecular mechanisms of circRNA FGFR3 (circFGFR3) in NSCLC progression remains unknown. Here, we used quantitative real-time polymerase chain reaction to validate that circFGFR3 expression was higher in NSCLC tissues than in the paratumor tissues. Furthermore, our study indicated that the forced circFGFR3 expression promoted NSCLC cell invasion and proliferation. Mechanistically, we found that circFGFR3 promoted NSCLC cell invasion and proliferation via competitively combining with miR-22-3p to facilitate the galectin-1 (Gal-1), p-AKT, and p-ERK1/2 expressions. Clinically, we revealed that the high circFGFR3 expression correlates with the poor clinical outcomes in patients with NSCLC. Together, these data provide mechanistic insights into the circFGFR3-mediated regulation of both the AKT and ERK1/2 signaling pathways by sponging miR-22-3p and increasing Gal-1 expression.

MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer.

Lysosomal-associated protein transmembrane 4 beta (LAPTM4B), a proto-oncogene, has been shown to be a positive modulator in cancer progression. However, the mechanism of LAPTM4B regulation is not fully elucidated. Aberrant microRNAs (miRNAs) can regulate gene expression by interfering with target transcripts and/or translation to exert tumor-suppressive or oncogenic effects in breast cancer. In the present study, miR-132-3p, which was predicted by relevant software, was confirmed to directly bind to the 3' untranslated region (3'UTR) of LAPTM4B and negatively regulate its expression in luciferase reporter and western blot assays. Subsequently, we validated that miR-132-3p was downregulated in breast cancer tissues. Receiver-operating characteristic curve analysis indicated that miR-132-3p had accurate diagnostic value, and a Kaplan-Meier and Cox regression model showed that miR-132-3p was a potential prognostic marker for recurrence, showing low levels in breast cancer patients. In addition, we showed that miR-132-3p was inversely correlated with LAPTM4B expression in the above samples. Functionally, miR-132-3p suppressed the migration and invasion of breast carcinoma cells through LAPTM4B by mediating epithelial-mesenchymal transition signals, and partially reversed the carcinogenic effects of LAPTM4B by inhibiting the PI3K-AKT-mTOR signaling pathway. Taken together, these findings provide the first comprehensive analysis of miR-132-3p as a direct LAPTM4B-targeted miRNA, and shed light on miR-132-3p/LAPTM4B as a significant functional axis involved in the oncogenesis and metastasis of breast cancer.

Long non-coding RNA SNHG15 promotes CDK14 expression via miR-486 to accelerate non-small cell lung cancer cells progression and metastasis.

Long non-coding RNAs (lncRNAs) have been validated to play important role in multiple cancers, including non-small cell lung cancer (NSCLC). In present study, our team investigate the biologic role of SNHG15 in the NSCLC tumorigenesis. LncRNA SNHG15 was significantly upregulated in NSCLC tissue samples and cells, and its overexpression was associated with poor prognosis of NSCLC patients. In vitro, loss-of-functional cellular experiments showed that SNHG15 silencing significantly inhibited the proliferation, promoted the apoptosis, and induced the cycle arrest at G0//G1 phase. In vivo, xenograft assay showed that SNHG15 silencing suppressed tumor growth of NSCLC cells. Besides, SNHG15 silencing decreased CDK14 protein expression both in vivo and vitro. Bioinformatics tools and luciferase reporter assay confirmed that miR-486 both targeted the 3'-UTR of SNHG15 and CDK14 and was negatively correlated with their expression levels. In summary, our study conclude that the ectopic overexpression of SNHG15 contribute to the NSCLC tumorigenesis by regulating CDK14 protein via sponging miR-486, providing a novel insight for NSCLC pathogenesis and potential therapeutic strategy for NSCLC patients.

Highly expressed long non-coding RNA CRNDE promotes cell proliferation through PI3K/AKT signalling in non-small cell lung carcinoma.

Recently, numerous studies have revealed that long non-coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non-small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigate the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT-PCR. The influence of CRNDE silencing or over-expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively. We also investigated the effect of abnormal CRNDE expression on cyclins and PI3K/AKT pathway. Furthermore, si-CRNDE NSCLC cell lines were injected subcutaneously into nude mice to explore tumour formation in vivo. The expression of CRNDE was significantly upregulated in NSCLC patients and cells. In addition, both loss and gain function assays revealed that CRNDE promoted NSCLC cell proliferation and growth both in vitro and in vivo. Moreover, CRNDE regulated the cell cycle transition from G0 /G1 stage to S stage and modulated the expression of CDK4, CDK6 and CCNE1. We further illustrated that CRNDE activated PI3K/AKT signalling in NSCLC cell lines. In conclusion, CRNDE was highly expressed in NSCLC malignant tissues and the heightened CRNDE strongly promoted NSCLC cell proliferation and growth through activating PI3K/AKT signalling; our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of NSCLC.

Nucleotides maintain the activity of Cav1.2 channels in guinea-pig ventricular myocytes.

The activity of Cav1.2 Ca(2+) channels is maintained in the presence of calmodulin and ATP, even in cell-free patches, and thus a channel ATP-binding site has been suggested. In this study, we examined whether other nucleotides, such as GTP, UTP, CTP, ADP and AMP, could be substituted for ATP in guinea-pig ventricular myocytes. We found that all the nucleotides tested could re-prime the Ca(2+) channels in the presence of 1 µM calmodulin in the inside-out mode. The order of efficacy was ATP > GTP > UTP > ADP > CTP ≈ AMP. Thus, the presumed nucleotide-binding site in the channel seemed to favor a purine rather than pyrimidine base and a triphosphate rather than a di- or mono-phosphate group. Furthermore, a high concentration (10 mM) of GTP, UTP, CTP, ADP and AMP had inhibitory effects on the channel activity. These results provide information on the putative nucleotide-binding site(s) in Cav1.2 Ca(2+) channels.

Is heme iron intake associated with risk of coronary heart disease? A meta-analysis of prospective studies.

PURPOSE: Heme iron may contribute to the development of atherosclerosis by catalyzing production of hydroxyl-free radicals and promoting low-density lipoprotein oxidation. However, epidemiologic findings regarding the association between heme iron intake and risk of coronary heart disease (CHD) are inconsistent. We aimed to investigate the association by carrying out a meta-analysis of prospective studies. METHODS: Relevant studies were identified by using PubMed and EMBASE databases between January 1966 and April 2013 and also by manually reviewing the reference lists of retrieved publications. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were computed using a random-effects model. RESULTS: Six prospective studies, which contained a total of 131,553 participants and 2,459 CHD cases, met the inclusion criteria. Combined results indicated that participants with higher heme iron intake had a 31% increased risk of CHD, compared with those with lower intake (RR = 1.31, 95% CI 1.04-1.67), with significant heterogeneity (P(heterogeneity) = 0.05, I(2) = 55.0%). Excluding the only study from Japan (limiting to Western studies) yielded a RR of 1.46 (95% CI 1.21-1.76), with no study heterogeneity (P(heterogeneity) = 0.44, I(2) = 0.0%). The dose-response RR of CHD for an increase in heme iron intake of 1 mg/day was 1.27 (95% CI 1.10-1.47), with low heterogeneity (P (heterogeneity) = 0.25, I (2) = 25.8%). We observed no significant publication bias. CONCLUSIONS: This meta-analysis suggests that heme iron intake was associated with an increased risk of CHD.

[Determination of organic acids and anions in exhaled breath by condensation collection-ion chromatography].

A non-invasive condensation collection-ion chromatography method was established for the determination of organic acids and anions including lactic acid, formic acid, acetic acid, pyruvic acid, chloride, nitrate, nitrite, and sulfate in the exhaled breath of humans. The breath exhaled was condensed and collected using a home-made exhaled breath condensation equipment. This equipment included a disposable mouthpiece as a blow-off port, one-way valve and flow meter, cold trap, disposable condensate collection tube placed in the cold trap, and gas outlet. A standard sampling procedure was used. Before collection, the collection temperature and sampling volume were set on the instrument control panel, and sampling was started when the cold-trap temperature dropped to the set value, while maintaining the balance. Subjects were required to gargle with pure water before sampling. During the sampling process, the subjects were required to inhale deeply until the lungs were full of gas and then exhale evenly through the air outlet. When the set volume was collected, the instrument made a prompt sound; then, the collection was immediately ended, the expiration time was recorded, and the average collection flow was calculated according to the expiration time and sampling volume. After collection, the disposable condensation collection tube was immediately taken out, sealed, and stored in the refrigerator at -20 ℃ away from light, and immediately used for further testing. The organic acids and anions in exhaled breath condensation (EBC) were filtered through a 0.22 µm membrane filter before injection and detected by ion chromatography with conductivity detection. Factors such as collection temperature and collection flow rate during condensation collection were optimized. The optimal cooling temperature was set at -15 ℃, and the optimal exhaled breath flow rate was set at 15 L/min. The mobile phase consisted of a mixture of sodium carbonate (1.5 mmol/L) and sodium bicarbonate (3 mmol/L). The flow rate was 0.8 mL/min, and the injection volume was 100 µL. An IC-SA3 column (250 mm×4.0 mm) was used, and the temperature was set at 45 ℃. An ICDS-40A electrodialysis suppressor was used, and the current was set at 150 mA. The linear ranges of the eight organic acids and anions were 0.1-10.0 mg/L; their correlation coefficients (r) were ≥0.9993. The limits of detection (LODs) for the eight organic acids and anions were 0.0017-0.0150 mg/L based on a signal-to-noise ratio of 3, and the limits of quantification (LOQs) were 0.0057-0.0500 mg/L based on a signal-to-noise ratio of 10. The intra-day precisions were 5.06%-6.33% (n=5), and the inter-day precisions were 5.37%-7.50% (n=5). This method was used to detect organic acids and anions in the exhaled breath of five healthy subjects. The contents of organic acids and anions in the exhaled breath were calculated. The content of lactic acid was relatively high, at 1.13-42.3 ng/L, and the contents of other seven organic acids and anions were 0.18-11.0 ng/L. During a 10 km-long run, the majority of organic acids and anions in the exhaled breath of five subjects first increased and then decreased. However, due to abnormal metabolism, the content changes of lactic acid, acetic acid, pyruvic acid and chloride in one subject were obviously different from others during exercise, showing a continuous rise. This method has the advantages of involving a simple sampling process and exhibiting good precision, few side effects, and no obvious discomfort or risk to the subjects. This study provides experimental ideas and a theoretical basis for future research on human metabolites.

D2 dopamine receptor antagonist raclopride induces non-canonical autophagy in cardiac myocytes.

Cell death by autophagy is an important means of maintaining cellular homeostasis in adult cardiac myocytes. Autophagy was previously shown to exert a cardioprotective effect, suggesting that modulation of autophagy pathways is a potential therapeutic strategy in the treatment of heart disease. Although dopamine is known to induce autophagy in neuroblastoma cells, the underlying mechanism and the types of dopamine receptors involved in this process remain unclear. In this study, we used various dopamine receptor antagonists and agonists to identify the specific dopamine receptor that mediates induction of autophagy. We evaluated autophagy induction by the expression of autophagy markers in neonatal rat ventricular cardiac myocytes. We evaluated intracellular calcium levels using Fluo-3/AM and demonstrated autophagy-induced morphological changes in cardiac myocytes using electron microscopy. We also examined the pathway for dopamine-induced autophagy using RNAi-mediated gene knockdown. Raclopride, the well-documented D2 receptor antagonist, significantly upregulated autophagy in cardiac myocytes via an mTOR-independent pathway. There was no difference in intracellular calcium levels between raclopride-treated cells and untreated cells. siRNA-mediated knockdown of Rab9 resulted in decreased expression of autophagy markers in raclopride-treated cells. Interestingly, siRNA-mediated knockdown of Atg7 resulted in a significant increase in Rab9 levels in raclopride-treated cells, suggesting that blocking the classical autophagy pathway results in activation of an alternative pathway. Our study suggests that (1) the D2 dopamine receptor plays a role in autophagy and (2) raclopride mediated a non-canonical autophagy pathway in cardiac myocytes via Rab9.

A high level of TM4SF5 is associated with human esophageal cancer progression and poor patient survival.

PURPOSE: We investigated expression of TM4SF5 and its involvement in human esophageal cancer (HEC). METHODS: We analyzed TM4SF5 expression in normal esophageal epithelial cells (HEEC), in four HEC cell lines, and in 20 HEC clinical tissue samples and matched nontumor samples. The effect of TM4SF5 on HEC cell proliferation and metastasis and invasion was assessed, and the relationship between TM4SF5 and integrin ß1 was determined. Finally, TM4SF5 and integrin ß1 expression were further examined by use of immunohistochemistry (IHC) and tissue microarray analysis, and the prognostic use of TM4SF5 and integrin ß1 in HEC was evaluated. RESULTS: TM4SF5 was more highly expressed in HEC cells and in HEC tissues than in HEEC and matched nontumor tissues. Down-regulation of TM4SF5 in KYSE150 cells reduced cell proliferation and metastasis and invasion whereas metastasis and invasion by KYSE510 increased after TM4SF5 cDNA transfection. In HEC cells, TM4SF5 formed a complex with integrin ß1, and interference with integrin ß1 in KYSE510-TM4SF5 cells markedly inhibited cell invasion on laminin 5. Our findings also showed that TM4SF5 and integrin ß1 overexpression correlated with low differentiation and high stage (p<0.05, respectively). Postoperative 5-year overall survival of patients with TM4SF5low and/or integrin ß1low was higher than for patients with TM4SF5high and/or integrin ß1high. Multivariate analysis demonstrated that TM4SF5 and integrin ß1 co-overexpression was an independent prognostic marker for HEC. CONCLUSION: TM4SF5 is positively associated with HEC invasiveness. The combination of TM4SF5 with integrin ß1 could potentially serve as a novel marker for predicting HEC prognosis.

Thulium laser vaporesection versus standard transurethral resection of the prostate: a randomized trial with transpulmonary thermodilution hemodynamic monitoring.

OBJECTIVES: To characterize the hemodynamics comparing thulium laser vaporesection of the prostate with traditional transurethral resection of the prostate. METHODS: A total of 80 consecutive patients with benign prostatic hyperplasia were randomly assigned into the thulium laser vaporesection of the prostate group or transurethral resection of the prostate group. Transpulmonary thermodilution hemodynamic monitoring was used before and 1 h after surgery to assess patient hemodynamics. Acute complications and treatment efficiency were evaluated after surgery. RESULTS: There were no statistical differences in age, prostate volume, anticoagulants and International Prostate Symptom Score between the two groups. The postoperative Stroke Volume Index was significantly higher in the thulium laser vaporesection of the prostate group (P = 0.007). The extravascular lung water and intrathoracic blood volume indices differed significantly pre- and postoperatively, and were similar in both groups. Decreases in serum sodium and hemoglobin concentrations after surgery were lower in the thulium laser vaporesection of the prostate group (P < 0.01). Acute complications, and improvements in International Prostate Symptom Score and maximum urinary flow rates, were similar in both groups. CONCLUSIONS: Transpulmonary thermodilution hemodynamic monitoring provides additional safety measures during surgical procedures. Thulium laser vaporesection of the prostate is associated with fewer hemodynamic changes and provides similar efficacy to transurethral resection of the prostate. Thus, it can be considered a safe and effective procedure.

Circular RNA hsa_circ_0004689 (circSWT1) promotes NSCLC progression via the miR-370-3p/SNAIL axis by inducing cell epithelial-mesenchymal transition (EMT).

BACKGROUND: Previous studies have reported the role of circular RNAs (circRNAs) in the progression of non-small-cell lung cancer (NSCLC). SWT1-derived circRNAs were confirmed to affect the apoptosis of cardiomyocytes; however, the biological functions of SWT1-derived circRNAs in cancers are still unknown. Here, we investigated the potential role of SWT1-derived circRNAs in NSCLC. METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression of circSWT1 in NSCLC tissues and paired normal tissues. The potential functions of circSWT1 in tumor progression were assessed by CCK-8, colony formation, wound healing, and matrigel transwell assays in vitro and by xenograft tumor models in vivo. Next, epithelial-mesenchymal transition (EMT) was evaluated by western blotting, immunofluorescence, and immunohistochemistry (IHC). Moreover, circRIP, RNA pulldown assays, luciferase reporter gene assays, and FISH were conducted to illuminate the molecular mechanisms of circSWT1 via the miR-370-3p/SNAIL signal pathway. Then, we knocked out SNAIL in A549 and H1299 cells to identify the roles of circSWT1 in the progression and EMT of NSCLC through SNAIL. Finally, circSWT1 functions were confirmed in vivo using xenograft tumor models. RESULTS: CircSWT1 expression was significantly upregulated in NSCLC tissues, and high expression of circSWT1 predicted poor prognosis in NSCLC via survival analysis. In addition, overexpression of circSWT1 promoted the invasion and migration of NSCLC cells. Subsequently, we found that overexpression of circSWT1 induced EMT and that knockdown of circSWT1 inhibited EMT in NSCLC cells. Mechanistically, circSWT1 relieved the inhibition of downstream SNAIL by sponging miR-370-3p. Moreover, we found that these effects could be reversed by knocking out SNAIL. Finally, we verified that circSWT1 promoted NSCLC progression and EMT in xenograft tumor models. CONCLUSION: CircSWT1 promoted the invasion, migration, and EMT of NSCLC. CircSWT1 could serve as a potential biomarker and a potential therapeutic target for NSCLC.

[Retrospective cohort study on application of acupuncture-aided anesthesia technique to patients undergoing thoracoscopic lobectomy].

OBJECTIVE: To compare the clinical effect of "initial scheme" and "improved scheme" of acupuncture-aided anesthesia for patients undergoing thoracoscopic lobectomy. METHODS: A retrospective analysis about 2 groups ("initial scheme" and "improved scheme") of patients (40 cases in each group) who underwent thoracoscopic lobectomy was conducted in the present paper. Patients of the "initial scheme" group received thoracoscopic operation with three incisions under acupuncture-aided anesthesia i.e., electroacupuncture (EA) stimulation of bilateral Hegu (LI4), Neiguan (PC6), Houxi (SI3) and Zhigou (SJ6), combined with Lidocaine and ropivacaine epidural anesthesia and propofol intravenous anesthesia from January of 2013 to December of 2017. Patients of the "improved scheme" group received thoracoscopic operation with single incision under acupuncture-aided anesthesia by EA, combined with ropivacaine paravertevinal block and lidocaine and remifentanil intravenous anesthesia from August 2018 to August 2021. The incidence of intraoperative deep breathing, resuscitation time, ambulatory rate on day after surgery and postoperative incision pain of the two schemes were compared. RESULTS: The incidence of intraoperative deep breathing and the degree of postoperative incision pain were significantly lower (P<0.05), the postoperative resuscitation time was obviously shorter (P<0.05), and the ambulatory rate on day after surgery was higher (P<0.05) in the "improved scheme" group than in the "initial scheme" group. CONCLUSION: The "improved scheme" is better than the "initial scheme" in stabilizing the patient's breathing during thoracoscopic lobectomy operation, shortening the resuscitation time, and ameliorating the postoperative recovery state and pain reaction, thus being a better technical solution in clinical practice.

Targeted delivery of pexidartinib to tumor-associated macrophages via legumain-sensitive dual-coating nanoparticles for cancer immunotherapy.

Tumor-associated macrophage (TAM) is regarded as an appealing cell target for cancer immunotherapy. However, it remains challenging to selectively eliminate M2-like TAM in tumor microenvironment. In this work, we employed a legumain-sensitive dual-coating nanosystem (s-Tpep-NPs) to deliver CSF-1R inhibitor pexidartinib (PLX3397) for targeting TAM therapy. The PLX3397-loaded NPs exhibited uniform size of ∼240 nm in diameter, good drug loading capacity and efficiency, as well as sustained drug release profile. Compared to non-sensitive counterpart ns-Tpep-NPs, s-Tpep-NPs showed distinguished selectivity upon M1 and M2 macrophage uptake with relation to incubation time and dose. Besides, the selectivity of anti-proliferation effect was also identified for s-Tpep-NPs against M1 and M2 macrophage. In vivo imaging demonstrated that s-Tpep-NPs exhibited much higher tumoral accumulation and TAM recognition specificity as compared to non-sensitive ns-Tpep-NPs. In vivo efficacy verified that s-Tpep-NPs formulation was much more effective than ns-Tpep-NPs and other PLX3397 formulations to treat B16F10 melanoma via targeting TAM depletion and modulating tumor immune microenvironment. Overall, this study provides a robust and promising nanomedicine strategy for TAM-targeted cancer immunotherapy.

Retroperitoneoscopic enucleation adrenalectomy: a viable surgical option for small nonsecreting adrenal tumors with low potential of malignancy.

Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.

Temperature fluctuation promotes the thermal adaptation of soil microbial respiration.

The magnitude of the feedback between soil microbial respiration and increased mean temperature may decrease (a process called thermal adaptation) or increase over time, and accurately representing this feedback in models improves predictions of soil carbon loss rates. However, climate change entails changes not only in mean temperature but also in temperature fluctuation, and how this fluctuation regulates the thermal response of microbial respiration has never been systematically evaluated. By analysing subtropical forest soils from a 2,000 km transect across China, we showed that although a positive relationship between soil microbial biomass-specific respiration and temperature was observed under increased constant incubation temperature, an increasing temperature fluctuation had a stronger negative effect. Our results further indicated that changes in bacterial community composition and reduced activities of carbon degradation enzymes promoted the effect of temperature fluctuation. This adaptive response of soil microbial respiration suggests that climate warming may have a lesser exacerbating effect on atmospheric CO2 concentrations than predicted.