Percutaneous nephrolithotomy for adult renal transplant de novo graft lithiasis: a single center analysis and systematic review of the literature.

INTRODUCTION/OBJECTIVE: Graft stones in renal transplant recipients pose a unique challenge, finding effective interventions to ensure optimal graft function and patient well-being. Various methods of stone clearance have been described for graft stones, including percutaneous nephrolithotomy (PCNL). While PCNL is a promising approach for managing graft stones, specific outcomes and associated characteristics for this approach have not been comprehensively evaluated before. This study aims to evaluate the safety and efficacy of the use of PCNL as the primary intervention of graft stones by assessing stone-free rates (SFR), treatment impact on graft function, and perioperative complications. METHODS: A retrospective clinical audit was performed for all transplants performed in a single center from 2007 to 2022, which included all graft lithiasis patients who were treated with PCNL. Both perioperative parameters and post-operative outcomes were collected. In addition, a systematic review including articles from MEDLINE, Embase, Web of Science yielded 18 full-text articles published between 1/1/2000 and 15/11/2023. The results pertaining to patients who underwent PCNLs for graft stones were cross-referenced and thoroughly evaluated. The review encompassed a comprehensive analysis of clinical data, postoperative outcomes, and procedural details. The protocol for the systematic review was prospectively registered on PROSPERO (CRD42023486825). RESULTS: In our center, 6 graft lithiasis patients were treated with PCNL. The initial SFR was 83.3%. SFR at 3 months and 1 year were both 100.0%. SFR at 3 years was 66.7%. Other centers reported initial SFR of 82.6-100.0% (interquartile range). SFR at 3 months, 1 year, 3 years was not well reported across the included studies. Incidence of graft lithiasis ranged from 0.44%-2.41%. Most common presentations at diagnosis were oliguria/anuria/acute kidney injury and asymptomatic. Reported complications included blood loss, transient hematuria, high urine output, sepsis, and damage to surrounding structures. The most commonly reported metabolic abnormalities in transplant lithiasis patients included hyperuricemia and hyperparathyroidism. CONCLUSION: PCNL is a practical and efficient choice for addressing graft lithiasis, demonstrating excellent stone clearance and minimal perioperative complications. These findings show the importance of PCNL as a primary intervention in this complex patient population.

Imaging of a novel ratio γ-glutamyl transpeptidase fluorescent probe in living cells and biopsies.

Herein, a novel fluorescent probe, GTP, was developed for monitoring the GGT (γ-glutamyl transpeptidase) level in living cells and biopsies. It consisted of the typical recognition group γ-Glu (γ-Glutamylcysteine) and the fluorophore (E)-4-(4-aminostyryl)-1-methylpyridin-1-ium iodide. With a ratio response between the signal intensity at 560 nm and 500 nm (RI560/I500), it could be important complement for the turn-on ones. With the linear range of 0-50 U/L, the limit of detection was calculated as 0.23 µM. The detection system showed the strongest response near pH 7.4, and exhibited steady fluorescence signals for at least 48 h. With high selectivity, good anti-interference and low cytotoxicity, GTP was suitable for physiological applications. By monitoring the GGT level with the ratio values in the green and blue channels, the probe GTP could distinguish cancer cells from normal cells. Furthermore, in the mouse tissues and humanization tissue samples, the probe GTP could also recognize the tumor tissues from the normal ones.

The effects of drinking bicarbonate-rich mineral water in calcium oxalate stone formers: an open label prospective randomized controlled study in an Asian cohort.

PURPOSE: To examine the effects of drinking bicarbonate-rich mineral water in patients with calcium oxalate stones. MATERIALS AND METHODS: This was an open label prospective randomized controlled study comparing the effects of a bicarbonate-rich mineral water versus plain water on urine biochemistry in patients with calcium oxalate stones. The mineral water group were instructed to consume 1.25 L of mineral water per day at meal times, and supplemented by plain water. Their total intake was up to 3 L/day. Control group consumed only plain water up to 3 L/day. 24 h urine analyses were performed at baseline, 1, 4, 8 and 12 weeks after starting protocol. RESULTS: 58 patients were recruited for the study. 51 patients were included in the final analysis. Baseline data were comparable between the two groups. Over the course of 12 weeks, compared to patients drinking plain water, those drinking mineral water had higher overall urinary volume (difference = 644.0 ml/24 h, 95% CI = (206.7, 1081.3)), higher overall urinary magnesium (difference = 1.894 mmol/24 h, 95% CI = (1.006, 2.782)), and pH (difference = 0.477, 95% CI = (0.149, 0.804)). However, there was no difference in urinary oxalate and Tiselius index. Mineral water group had net increase of urinary citrate (at each study point compared to baseline) which was sustained until week 12, whereas plain water group showed no significant change. CONCLUSIONS: Drinking bicarbonate-rich mineral water in calcium oxalate stone formers increased stone inhibitors such as magnesium, citrate and moderate degree of urinary alkalinization compared to patients drinking plain water, but it did not alter Tiselius index or urinary oxalate after 12 weeks.

[Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide]. / ç»ä¸€æ°§åŒ–æ°®å¸å ¥æ²»ç–—çš„æ–°ç”Ÿå„¿æŒç»­è‚ºåŠ¨è„‰é«˜åŽ‹æ‚£å„¿æ­»äº¡çš„æ—©æœŸå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO). METHODS: A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk. RESULTS: A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2. CONCLUSIONS: Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

A three-channel fluorescent probe for selective detection of ONOO- and its application to cell imaging.

The fluorescent probe, GXY-ADP-2, with xanthene structure as the fluorescent core was designed and prepared for the selective detection of peroxynitrite (ONOO-). ONOO- can be produced endogenously and exogenously and is a strong oxidant with a short half-life. Oxidative modifications of biomolecules, that can be attributed to the formation of ONOO-, occur in the reactions of biomolecules with secondary ONOO--derived radical oxidants. Therefore, it is very important to develop a specific fluorescent probe for detecting ONOO- to monitor oxidative stress state. The excitation wavelength and emission wavelength of the probe are 689 nm and 739 nm respectively. In the process of co-incubation with ONOO-, generate a new substance with two internal conjugated structures through a special reaction mechanism, one giving the fluorescence with the excitation wavelength of 347 nm and the emission wavelength of 484 nm with the detection limit of 0.12 µM, and the other that with the excitation wavelength of 433 nm and the emission wavelength of 583 nm with the detection limit of 0.077 µM. The linear dynamic range of the probe is 0-5 µM. Its response is not affected by the other reactive oxygen species, thus can sensitively detect ONOO-. In bioimaging experiments with HepG2 cells, the green and blue cell fluorescence signals (583 nm and 433 nm, respectively) were increased, while the red one (739 nm) was significantly reduced, under lipopolysaccharide (LPS) induced oxidative stress, proving that the probe could sensitively detect ONOO- in living cells. This work provides a new tool for the dynamic changes of ONOO- and oxidative stress processes in biological systems.

Therapeutic Targeting of Nrf2 Signaling by Maggot Extracts Ameliorates Inflammation-Associated Intestinal Fibrosis in Chronic DSS-Induced Colitis.

Intestinal fibrosis is induced by excessive myofibroblast proliferation and collagen deposition, which has been regarded as a general pathological feature in inflammatory bowel disease (IBD). Therefore, identifying clinical markers and targets to treat and prevent intestinal fibrosis is urgently needed. The traditional Chinese medicine maggot, commonly known as "wu gu chong", has been shown to reduce oxidative stress and alleviate inflammation in chronic colitis. This study investigated the mechanisms underlying the effects of maggot extract (ME) on inflammation-associated intestinal fibrosis in TGF-ß1-stimulated human intestinal fibroblasts (CCD-18Co cells) and dextran sodium sulphate (DSS)-induced chronic colitis murine model. To assess the severity of inflammation and fibrosis, histological and macroscopic evaluation were carried out. The results showed that ME was a significant inhibitor of body weight loss and colon length shortening in mice with chronic colitis. In addition, ME suppressed the intestinal fibrosis by downregulating TGF-ß1/SMADs pathway via upregulation of Nrf2 expression at both protein and mRNA levels. ME markedly increased the expression of Nrf2, thus resulting in a higher level of HO-1. After treatment with Nrf2 inhibitor (ML385) or siRNA-Nrf2 for deactivating Nrf2 pathway, the protective effects of ME were abolished both in vitro and in vivo. Moreover, the histopathological results for the major organs of DSS mice treated with ME showed no signs of clinically important abnormalities. Treatment with ME had no effect on the viability of CCD-18Co cells, suggesting its low in vitro cytotoxicity. Furthermore, ME could mediate intestine health by keeping the balance of the gut microbes through the enhancement of beneficial microbes and suppression of pathogenic microbes. In conclusion, this is the first ever report demonstrating that ME ameliorates inflammation-associated intestinal fibrosis by suppressing TGF-ß1/SMAD pathway via upregulation of Nrf2 expression. Our findings highlight the potential of Nrf2 as an effective therapeutic target for alleviating intestinal fibrosis.

Manganese dioxide (MnO2) based nanomaterials for cancer therapies and theranostics.

Today, cancer still poses a serious threat to human, but there is no exact cure. Therefore, exploring to accomplish high therapeutic performance is a challenging and urgent task. Since the nanoparticles unique properties were discovered, they have displayed promising potential for more effective therapies and have been widely used in photodynamic therapy (PDT) and radiation therapy (RT). However, some special properties of the tumour microenvironment (TME) have seriously affected the therapeutic outcomes, so the modulation of the TME becomes critical. Manganese dioxide (MnO2), as a transition metal oxide, has been widely used in biomedical fields with special physical and chemical properties, especially in regulating the TME. Furthermore, MnO2 has widely applications in various cancer treatments, such as PDT, chemodynamic therapy (CDT), immunotherapy, and some specific collaborative treatment. Herein, we reviewed the recent applications of MnO2 modified nanomaterials in tumour therapies and theranostics, including TME regulation, controlled drug loading/delivery/release, and imaging.

Corrigendum to "Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2".

[This corrects the article DOI: 10.1155/2019/4703253.].

Survival outcomes of Asian younger men (< 55 years) undergoing radical prostatectomy: a review of prostate cancer database in a tertiary hospital in Singapore.

PURPOSE: Prostate cancer largely affects older men. This study aims to investigate prostate cancer in younger men (< 55 years) to shed light on the survival outcomes of this unique subset of patients in Asian context. METHODS: Data were obtained from the Singapore General Hospital Prostate Cancer Registry. Data on all men with clinically organ confined prostate cancer who underwent radical prostatectomy between 1998 and 2016 were obtained from the registry. Tumor characteristics, follow-up data, and cause of death were acquired. RESULTS: A total of 1120 men underwent radical prostatectomy between 1998 and 2016. Of these, 12 were aged ≤ 44 years, 106 were aged 45-54 years, 596 were aged 55-64, 397 were aged 65-74 and 9 were aged ≥ 75. There was no difference across age groups when comparing Gleason ≤ 7 vs Gleason ≥ 8 disease, T1/2 vs T3/4 disease and the median PSA values were similar. No difference was observed in overall survival or prostate cancer specific survival among 4 age groups (≤ 44, 45-54, 55-64, 65-74) (p = 0.156 and p = 0.227 respectively). Although there was a trend of increasing rate of biochemical recurrence for older patients, it's not statistically significant (p = 0.157). Time to biochemical recurrence was similar as well (p = 0.257). CONCLUSION: This large cohort of Asian patients who underwent radical prostatectomy did not show significant age-related differences in important parameters and outcomes.

Evaluation of neutrophil-to-lymphocyte ratio as a prognostic indicator in a Singapore cohort of patients with clinically localized prostate cancer treated with prostatectomy.

PURPOSE: Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as easily assessable markers of systemic inflammation and has been shown to represent a prognostic marker in prostate cancer in previous studies. METHODS: Data from 668 patients with localized prostate cancer treated with prostatectomy (open and robot assisted) in Singapore General Hospital from 1998 to 2014 were analyzed. Correlation between NLR and histopathological status was analyzed. Association between NLR and distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), and biochemical disease-free survival (BDFS) was assessed. RESULTS: NLR was not significantly correlated with histopathological status, including Gleason score (≤ 6 versus 7 versus ≥ 8, p = 0.159), lymph node metastasis (negative versus positive, p = 0.159), or surgical margin status (negative versus positive, p = 0.494). NLR was categorized into two groups (< median and ≥ median, median = 2.09) and NLR ≥ 2.09 was not a prognostic factor for decreased MFS (p = 0.609), CSS (p = 0.302), OS (p = 0.722) and BDFS (p = 0.589). No difference was observed for NLR even in high-risk subgroup patients compared to the rest (p = 0.058). The area under the ROC curve (AUC) of NLR as a prognosticator for biochemical recurrence was only 0.53. CONCLUSION: Our findings indicate that pre-treatment NLR may not predict prognosis in patients with localized prostate cancer treated with prostatectomy in an Asian cohort.

Tubulin Inhibitors Binding to Colchicine-Site: A Review from 2015 to 2019.

Due to the three domains of the colchicine-site which is conducive to the combination with small molecule compounds, colchicine-site on the tubulin has become a common target for antitumor drug development, and accordingly, a large number of tubulin inhibitors binding to the colchicine-site have been reported and evaluated over the past years. In this study, tubulin inhibitors targeting the colchicine-site and their application as antitumor agents were reviewed based on the literature from 2015 to 2019. Tubulin inhibitors were classified into ten categories according to the structural features, including colchicine derivatives, CA-4 analogs, chalcone analogs, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them displayed potent antitumor activity, including antiproliferative effects against Multi-Drug-Resistant (MDR) cell lines and antivascular properties, both in vitro and in vivo. In this review, the design, synthesis and the analysis of the structure-activity relationship of tubulin inhibitors targeting the colchicine-site were described in detail. In addition, multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo are further listed in tables to present a clear picture of potent tubulin inhibitors, which could be beneficial for medicinal chemistry researchers.

Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2.

Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as "wu gu chong." NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1ß, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.

Rapid and Sensitive Detection of Salmonella in Chickens Using Loop-Mediated Isothermal Amplification Combined with a Lateral Flow Dipstick.

Salmonellosis is a highly contagious bacterial disease that threatens both human and poultry health. Tests that can detect Salmonella in the field are urgently required to facilitate disease control and for epidemiological investigations. Here, we combined loop-mediated isothermal amplification (LAMP) with a chromatographic lateral flow dipstick (LFD) to rapidly and accurately detect Salmonella. LAMP primers were designed to target the Salmonella invA gene. LAMP conditions were optimized by adjusting the ratio of inner to outer primers, MgSO4 concentration, dNTP mix concentration, amplification temperature, and amplification time. We evaluated the specificity of our novel LAMP-LFD method using six Salmonella species and six related non-Salmonella strains. All six of the Salmonella strains, but none of the non-Salmonella strains, were amplified. LAMP-LFD was sensitive enough to detect concentrations of Salmonella enterica subsp. enterica serovar Pullorum genomic DNA as low as 89 fg/µl, which is 1,000 times more sensitive than conventional PCR. When artificially contaminated feed samples were analyzed, LAMP-LFD was also more sensitive than PCR. Finally, LAMP-LFD gave no false positives across 350 chicken anal swabs. Therefore, our novel LAMP-LFD assay was highly sensitive, specific, convenient, and fast, making it a valuable tool for the early diagnosis and monitoring of Salmonella infection in chickens.

Platelet-Derived Microparticles: A New Index of Monitoring Platelet Activation and Inflammation in Kawasaki Disease.

OBJECTIVE: To investigate the dynamic changes of platelet-derived microparticles (PDMP) in Kawasaki disease (KD) and its clinical significance and to study its relationship with intravenous immunoglobulin (IVIG) resistance, inflammatory indicators and aspirin treatment in children with KD. METHODS: Twenty children with KD were enrolled as the experimental group, while 20 age- and gender-matched children with common febrile disease were included in the control group. Blood samples were drawn before and 7-10 d after IVIG infusion and thereafter at 1, 2, and 3 mo after the onset of KD to estimate the PDMP concentrations by enzyme linked immunosorbent assay (ELISA). C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and cytokines [Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and Soluble interleukin-2 (sIL-2R)] were also measured. RESULTS: The level of PDMP in KD children before IVIG was significantly higher than that in controls (P < 0.0001). The PDMP level in KD children decreased significantly at 7 to 10 d after IVIG (P < 0.0001) and then decreased to the lowest level in the course of 1 to 2 mo. Some children's PDMP level rebounded in the course of 3 mo (P = 0.047). In addition, the mean level of PDMP in IVIG-resistant children was higher than that in IVIG-effective children; however, there was no significant difference between the two groups (P = 0.1945). Furthermore, PDMP was positively correlated with hs-CRP, IL-6, and sIL-2R levels, but no correlation was observed with ESR, PCT, and TNF-α levels. CONCLUSIONS: PDMP can be used as an index to monitor inflammation in children at the acute stage of KD. And the duration of platelet activation in KD is individualized.

Exploratory analysis of introducing next-generation sequencing-based method to treatment-naive lung cancer patients.

BACKGROUND: The utilization of cancer-linked genetic alterations for categorizing patients against optimal treatment is becoming increasingly popular, especially in non-small cell lung cancer (NSCLC). However, disadvantages of the conventional techniques, such as the low throughput and limited detectable alteration types, lead to the demand of large-scale parallel sequencing for different forms of genetic variants. METHODS: We evaluated the potential of performing next-generation sequencing (NGS)-based methods in a cohort of 61 treatment-naive NSCLC patients to profile their driver mutations, using a panel consisting of 8 well-established driver genes of lung cancer. RESULTS: Our data revealed that 80% of patients harbored driver mutations. Moreover, our data revealed a few rare mutations, such as BRAF K601E and EGFR exon 20 insertion, which cannot be detected using commercially available single gene testing kits of conventional methods. We detected one patient with dual driver mutations. Next, correlations between driver mutations and clinical characteristics were interrogated in this cohort. Our results revealed that EGFR alterations were positively correlated with early stage, adenocarcinoma, alveolar and papillary component, TTF1 expression, and negatively correlated with P40 and Ki67 expression. ERBB2 alterations were associated with younger age and micro-invasive feature of tumor. Rearrangements of ALK indicated tumor relapse. CONCLUSIONS: Our study highlights the potential of NGS-based methods in treatment-naive patients, thus paving its way for routine clinical use. Investigation of clinical correlation of driver mutations might be helpful for clinicians in cancer diagnosis and has implications for seeking patients with specific gene alteration in clinical studies.

Dihydropyrazothiazole derivatives as potential MMP-2/MMP-8 inhibitors for cancer therapy.

MMP-2/MMP-8 is established as one of the most important metalloenzymes for targeting cancer. A series of dihydropyrazothiazole derivatives (E1-E18) bearing a salicylaldehyde group linked to Pyrazole ring were designed, synthesized, and evaluated for their pharmacological activity as MMP-2/MMP-8 inhibitors. Among them, compound E17 exhibited most potent inhibitory activity (IC50 = 2.80 µM for MMP-2 and IC50 = 5.6 µM for MMP-8), compared to the positive drug CMT-1 (IC50 = 1.29 µM). Compounds (E1-E18) were scrutinized by CoMFA and CoMSIA techniques of Three-dimensional quant. structure-activity relationship (3D-QSAR), as well as a docking simulation. Moreover, treatment with compound E4 could induce MCF-7 cell apoptosis. Overall, the biological profile of E1-E18 may provide a research basis for the development of new agents against cancer.

Influence of nodal status on the surgical outcome for bronchogenic carcinoma involving the carina: a systematic review and meta-analysis.

INTRODUCTION: Bronchogenic carcinomas involving the carina or the tracheo-bronchial angle represents a challenging surgical procedure because of difficult surgical techniques and complex ventilation procedures. Even though surgical outcomes for this type of procedure has improved over time, the need for surgical management of patients with metastatic mediastinal nodes, that is those that are graded N2 or higher according to the TNM classification, is still controversial. EVIDENCE ACQUISITION: We searched PubMed, Embase, and CNKI for literature in English or Chinese reporting on this subject, with information on survival rates or survival curves for groups with different grades of nodal status. We then performed a meta-analysis by grouping N0 and N1 patients and compared the surgical outcomes to those graded as N2 or higher. Hazard Ratios for each study were derived from the Kaplan-Meier survival curve. EVIDENCE SYNTHESIS: Seven studies were included in this meta-analysis. The calculated hazard ratios ranged from 0.146 to 0.455. The weighted average hazard ratio for the N0/N1 group as compared to the N2/N3 group was 0.261 (CI: 0.154-0.441). The Galbraith plot confirmed the homogeneity of the studies included. CONCLUSIONS: Carinal resection and reconstruction remains a challenging surgical procedure and the rather poor surgical outcomes for patients graded as N2 or higher, according to nodal involvement points to the fact that better pre-operative management is required in terms of tumor grading, induction chemotherapy and radiotherapy to decrease the risks associated with metastatic mediastinal nodal status.

Palladium-catalyzed direct C(sp3)-H arylation of indole-3-ones with aryl halides: a novel and efficient method for the synthesis of nucleophilic 2-monoarylated indole-3-ones.

A novel and efficient method for the synthesis of nucleophilic 2-monoarylated indole-3-ones via palladium-catalyzed direct C(sp3)-H arylation of indole-3-ones with aryl halides has been developed. Various 2-monoarylated indole-3-ones were readily obtained with yields up to 95%. As a class of important nucleophilic intermediates, 2-monoarylated indole-3-ones can be used for the construction of C2-quaternary indolin-3-one skeletons.

The miR-875-5p inhibits SATB2 to promote the invasion of lung cancer cells.

The pathogenesis of non-small cell lung cancer (NSCLC) is regulated by various miRNAs. In this study, we identified that miR-875-5pis up-regulated in NSCLC patients, and inhibited SATB Homeobox 2(SATB2) to promote proliferation and invasion of NSCLCcells.CCK-8assay revealed thatmiR-875-5p mimics promoted proliferation of NSCLC cells. Transwell assay showed that miR-875-5pmimicspromoted the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-875-5pdirectly binds to the 3'untranslated region of SATB2, and western blotting showed that miR-875-5psuppresses the expression of SATB2 at the protein level. Moreover, the inhibitors of miR-875-5pinhibit proliferation and invasion of NSCLC cell lines. The miR-875-5pwouldbe a potential therapeutic target for NSCLC treatment in the future.

Which is best method for instillation of topical therapy to the upper urinary tract? An in vivo porcine study to evaluate three delivery methods

ABSTRACT Purpose: To compare the staining intensity of the upper urinary tract (UUT) urothelium among three UUT delivery methods in an in vivo porcine model. Materials and methods: A fluorescent dye solution (indigo carmine) was delivered to the UUT via three different methods: antegrade perfusion, vesico-ureteral reflux via in-dwelling ureteric stent and retrograde perfusion via a 5F open-ended ureteral catheter. Twelve renal units were tested with 4 in each method. After a 2-hour delivery time, the renal-ureter units were harvested en bloc. Time from harvesting to analysis was also standardised to be 2 hours in each arm. Three urothelium samples of the same weight and size were taken from each of the 6 pre-defined points (upper pole, mid pole, lower pole, renal pelvis, mid ureter and distal ureter) and the amount of fluorescence was measured with a spectrometer. Results: The mean fluorescence detected at all 6 predefined points of the UUT urothelium was the highest for the retrograde method. This was statistically significant with p-value less than <0.05 at all 6 points. Conclusions: Retrograde infusion of UUT by an open ended ureteral catheter resulted in highest mean fluorescence detected at all 6 pre-defined points of the UUT urothelium compared to antegrade infusion and vesico-ureteral reflux via indwelling ureteric stents indicating retrograde method ideal for topical therapy throughout the UUT urothelium. More clinical studies are needed to demonstrate if retrograde method could lead to better clinical outcomes compared to the other two methods.