Assessment of the capability of cadmium accumulation and translocation among 31 willows: four patterns of willow biomass variation response to cadmium.

Cadmium (Cd) pollution threatens food security and the environment. Willow species (Salix, Salicaceae) exhibit a remarkable potential to restore Cd-polluted sites due to their high biomass production and high Cd accumulation capacities. This study examined the Cd accumulation and tolerance in 31 genotypes of shrub willow in hydroponic conditions at varying Cd levels (0 µM Cd, 5 µM Cd, and 20 µM Cd). The root, stem, and leaf biomass of 31 shrub willow genotypes showed significant differences to Cd exposure. Among 31 willow genotypes, four patterns of biomass variation response to Cd were identified: insensitive to Cd; growth inhibition due to excessive Cd supply (high Cd inhibition); low Cd causing inhibited growth, whereas high Cd leading to increased biomass (U-shape); and growth increment with excessive Cd exposure (high Cd induction). The genotypes belonging to the "insensitive to Cd" and/or "high Cd induction" were candidates for the utilization of phytoremediation. Based on the analysis of Cd accumulation of 31 shrub willow genotypes at high and low Cd levels, genotypes 2372, 51-3, and 1052 obtained from a cross between S. albertii and S. argyracea grew well and accumulated relatively more Cd levels than other genotypes. In addition, for Cd-treated seedlings, root Cd accumulation was positively correlated with shoot Cd accumulation and total Cd uptake, demonstrating that Cd accumulation in roots could serve as a biomarker for evaluating the Cd extraction capacity of willows, especially in hydroponics screening. The results of this study screened out willow genotypes with high Cd uptake and translocation capacities, which will provide valuable approaches for restoring Cd-contaminated soils with willows.

Clinicopathologic factors linked to oncologic outcomes for renal cell carcinoma with sarcomatoid dedifferentiation: A PRISMA-compliant systematic review and meta-analysis.

Background: There are still differences in the prognostic factors of renal cell carcinoma with sarcomatoid dedifferentiation (sRCC). The aim of this study was to evaluate important predictors of survival in patients with sRCC. Patients and methods: A comprehensive search of PubMed, Embase, and Cochrane Library was conducted to identify eligible studies. The endpoints embraced overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Hazard ratios (HRs) and related 95% confidence intervals (CIs) were extracted. Results: A total of 13 studies were included for analyses. The pooled results showed that high European Cooperative Oncology Group performance score (HR 2.39, 95% CI 1.32-4.30; P = 0.004), high T stage (HR 2.18, 95% CI 1.66-2.86; P < 0.001), positive lymph node (HR 1.54, 95% CI 1.40-1.69; P < 0.001), distant metastasis (HR 2.52, 95% CI 1.99-3.21; P < 0.001), lung metastases (HR 1.45, 95% CI 1.16-1.80; P < 0.001), liver metastases (HR 1.71, 95% CI 1.30-2.25; P < 0.001), tumor necrosis (HR 1.78, 95% CI 1.14-2.80; P = 0.010), and percentage sarcomatoid ≥50% (HR 2.35, 95% CI 1.57-3.52; P < 0.001) were associated with unfavorable OS. Positive lymph node (HR 1.57, 95% CI 1.33-1.85; P < 0.001) and high neutrophil to lymphocyte ratio (HR 1.16, 95% CI 1.04-1.29; P = 0.008) were associated with unfavorable CSS. High T stage (HR 1.93 95% CI 1.44-2.58; P < 0.001) was associated with unfavorable progression-free survival. Conclusions: A meta-analysis of available data identified important prognostic factors for CSS, OS, and PFS of sRCC, which should be systematically evaluated for patient counseling, risk stratification, and treatment selection. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=249449.

Comparison of two willow genotypes reveals potential roles of iron-regulated transporter 9 and heavy-metal ATPase 1 in cadmium accumulation and resistance in Salix suchowensis.

Willows (Salix spp.) are promising extractors of cadmium (Cd), with fast growth, high biomass production, and high Cd accumulation capacity. However, the molecular mechanisms underlying Cd uptake and detoxification are currently poorly understood. Analysis of the Cd uptake among 30 willow genotypes in hydroponic systems showed that the S. suchowensis and S. integra hybrids, Jw8-26 and Jw9-6, exhibited distinct Cd accumulation and resistance characteristics. Jw8-26 was a high Cd-accumulating and tolerant willow, while Jw9-6 was a low Cd-accumulating and relatively Cd-intolerant willow. Therefore, these two genotypes were ideal specimens for determining the molecular mechanisms of Cd uptake and detoxification. To identify relevant genes in Cd handling, the parent S. suchowensis was treated with Cd and RNA-seq analysis was performed. SsIRT, SsHMA, and SsGST, in addition to the transcription factors SsERF, SsMYB, and SsZAT were identified as being associated with Cd uptake and resistance. Because membrane-localised heavy metal transporters mediate Cd transfer to plant tissues, a total of 17 SsIRT and 12 SsHMA family members in S. suchowensis were identified. Subsequently, a thorough bioinformatics analysis of the SsIRT and SsHMA families was conducted, and their transcript levels were analysed in the roots of the two hybrids. The transcript levels of SsIRT9 in roots were positively correlated with the observed differences in Cd accumulation in Jw8-26 versus Jw9-6. Jw8-26 displayed higher SsIRT9 expression levels and higher Cd accumulation than Jw9-6; therefore, SsIRT9 may be involved in Cd uptake. Gene expression analysis also revealed that SsHMA1 was a candidate gene associated with Cd resistance. These results lay the foundation for understanding the molecular mechanism of Cd transfer and detoxification in willows, and provide guidance for the screening and breeding of high Cd-accumulating and tolerant willow genotypes via genetic engineering.

Prognostic Role of Pretreatment C-Reactive Protein to Albumin Ratio in Urological Cancers: A Systematic Review and Meta-Analysis.

Background: To investigate the potential prognostic role of C-reactive protein to albumin ratio (CAR) in patients with urinary cancers, including renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC). Methods: We searched and screened literatures with PubMed, Embase, Cochrane Library, and Web of Science in January 2022. We applied combined hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the associations. Results: Thirteen studies including 2,941 cases were analyzed in our study. Merged results indicated that highly pretreated CAR was associated with inferior overall survival (HR 2.21, 95% CI 1.86-2.62, p < 0.001) and progression-free survival (HR 1.85, 95% CI 1.36-2.52, p < 0.001) for urinary cancers. In a subgroup analysis of OS by tumor type, CAR can be a predictor in RCC (HR 2.10, 95% CI 1.72-2.56), BC (HR 3.35, 95% CI 1.94-5.80), and PC (HR 2.20, 95% CI 1.43-3.37). In a subgroup analysis of PFS by tumor type, CAR can be a predictor in BC (HR 1.76, 95% CI 1.03-3.02), and RCC (HR 1.90, 95% CI 1.25-2.89). The reliability and robustness of results were confirmed. Conclusions: High pretreated CAR was effective predictor of poor survival in patients with urinary cancers and can act as prognostic factor for these cases. Systematic Review Registration: PROSPERO (CRD42022306414).

Comparison of outcomes between laparoscopic and robot-assisted partial nephrectomy for complex renal tumors: RENAL score ≥7 or maximum tumor size >4 cm.

INTRODUCTION: We reviewed current studies and performed a meta-analysis to compare outcomes between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) treating complex renal tumors (RENAL score ≥7 or maximum clinical tumor size >4 cm). EVIDENCE ACQUISITION: Using the databases of PubMed, Embase, and the Cochrane Library, a comprehensive literature search was performed in April, 2020. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model. Publication bias was evaluated by funnel plots. EVIDENCE SYNTHESIS: Ten observational studies including 5193 patients (LPN: 1574; RAPN: 3619) were included. There was no significant difference between the two groups regarding conversion to open (P=0.07) surgery, all complications (P=0.12), grade 1-2 complications (P=0.10), grade 3-5 complications (P=0.93), operative time (P=0.94), estimated blood loss (P=0.17). Patients undergoing LPN had a significant higher rate of conversion to radical (OR=4.33; 95% CI: 2.01-9.33; P<0.001), a longer ischemia time (IT, P<0.001; WMD=3.02 min; 95% CI: 1.67 to 4.36), a longer length of stay (LOS, P<0.001; WMD=0.67 days; 95% CI: 0.35 to 0.99), a lower rate of positive surgical margin (P=0.03; OR=0.71; 95% CI: 0.53 to 0.96), a greater eGFR decline (P<0.001; WMD=2.41 mL/min/1.73 m2; 95% CI: 1.22 to 3.60), a higher rate of CKD upstaging (P<0.001; OR=2.44; 95% CI: 1.54 to 3.87). No obvious publication bias was observed. CONCLUSIONS: For complex renal tumors, RAPN is more favorable than LPN in terms of lower rate of conversion to radical surgery, shorter IT, shorter LOS, less eGFR decline, and lower rate of CKD upstaging. Methodological limitations of observational studies should be taken into account in interpreting these results.

PSANet: Pyramid Splitting and Aggregation Network for 3D Object Detection in Point Cloud.

3D object detection in LiDAR point clouds has been extensively used in autonomous driving, intelligent robotics, and augmented reality. Although the one-stage 3D detector has satisfactory training and inference speed, there are still some performance problems due to insufficient utilization of bird's eye view (BEV) information. In this paper, a new backbone network is proposed to complete the cross-layer fusion of multi-scale BEV feature maps, which makes full use of various information for detection. Specifically, our proposed backbone network can be divided into a coarse branch and a fine branch. In the coarse branch, we use the pyramidal feature hierarchy (PFH) to generate multi-scale BEV feature maps, which retain the advantages of different levels and serves as the input of the fine branch. In the fine branch, our proposed pyramid splitting and aggregation (PSA) module deeply integrates different levels of multi-scale feature maps, thereby improving the expressive ability of the final features. Extensive experiments on the challenging KITTI-3D benchmark show that our method has better performance in both 3D and BEV object detection compared with some previous state-of-the-art methods. Experimental results with average precision (AP) prove the effectiveness of our network.

Prognostic Role of Serum Lactate Dehydrogenase in Patients With Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Background: To investigate the potential prognostic role of serum lactate dehydrogenase (LDH) in patients with urothelial carcinoma (UC) using the method of systematic review and meta-analysis. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies up to February 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the relationship. Results: A total of 14 studies including 4,009 patients with UC were incorporated. The results showed that a high pretreatment serum LDH was associated with an inferior overall survival (OS, HR 1.61, 95% CI 1.39-1.87, p < 0.001), cancer-specific survival (CSS, HR 1.41, 95% CI 1.05-1.90, p = 0.022), and disease-free survival (DFS, HR 1.64, 95% CI 1.04-2.59, p = 0.034) in UC. Subgroup analyses identified that a high pretreatment serum LDH was associated with a poor OS (HR 1.97, 95% CI 1.02-3.81, p = 0.042) and DFS (HR 1.64, 95% CI 1.04-2.59, p = 0.034) in upper tract urothelial carcinoma, a short OS (HR 1.71, 95% CI 1.37-2.15, p < 0.001) in urothelial carcinoma of bladder. Conclusion: Our findings indicated that a high level of pretreatment serum LDH was associated with inferior OS, CSS, and DFS in patients with UC. This biomarker can be an important factor incorporated into the prognostic models for UC.

Androgen Receptor Is Inactivated and Degraded in Bladder Cancer Cells by Phenyl Glucosamine via miR-449a Restoration.

BACKGROUND Bladder cancer caused by exposure to aniline dyes, chronic cystitis, and smoking is detected in approximately 70 000 new cases annually. In the USA alone, it leads to 15 000 deaths every year. In the present study, we investigated the role of 3-((4'-amino-[1,1'-biphenyl]-4-yl)amino)-4-bromo-5-oxo-2,5-dihydrofuran-2-yl acetate (ABDHFA) in the inhibition of bladder cancer cell viability. MATERIAL AND METHODS Viability of cells was examined using MTT assay and distribution of cell cycle was assessed by flow cytometry. Expression of cyclin D1, androgen, prostate-specific antigen (PSA), and miR-449a was analyzed using Western blot and quantitative real-time polymerase chain reaction assays. RESULTS The results demonstrated that ABDHFA treatment inhibited viability of UMUC3 and TCCSUP AR-positive bladder cancer cells. ABDHFA treatment led to break-down of AR in UMUC3 and TCCSUP cells after 48 h in a dose-dependent manner. Up-regulation of miR-449a by lentivirus transfection down-regulated the AR signalling pathway. In UMUC3 and TCCSUP cells, ABDHFA treatment led to inhibition of mRNA and protein expression corresponding to AR. CONCLUSIONS In summary, the present study demonstrates that proliferation of AR-positive bladder carcinoma cells is markedly reduced by ABDHFA treatment through arrest of cell cycle and degradation of AR protein. Thus, ABDHFA, a novel compound, can be used for the treatment of bladder cancer.

Direct targeting of MAPK8IP1 by miR-10a-5p is a major mechanism for gastric cancer metastasis.

MicroRNA (miRNA) are endogenous non-coding RNAs that suppress gene expression at the transcriptional, post-transcriptional or translational level by targeting the 3'-UTRs of specific mRNAs. miR-10a has been frequently reported to be aberrantly overexpressed in human tumors. In gastric cancer (GC), miR-10a has an important role in the metastasis from primary GC to lymph nodes. However, the role and relevant pathways of miR-10a in GC metastasis remain largely unknown. The present study was performed using 41 GC and 20 normal gastric mucosa tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that MAPK8IP1 was significant downregulated in GC tissue. A statistically significant inverse correlation was detected between miR-10a and MAPK8IP1 mRNA expression levels in GC specimens. Luciferase reporter assay and qPCR results suggested that MAPK8IP1 was a direct target of miR-10a in GC cells. Matrigel invasion assay and wound-healing assay results showed that MAPK8IP1 overexpression rescued the increased migration ability of miR-10a effectors in MKN45 cells. Furthermore, the underlying mechanism of miR-10a functions in GC was explored. The findings indicated that miR-10a-5p directly targets MAPK8IP1, as a major mechanism for gastric cancer metastasis. The results of the present study suggested that miR-10a may be a potential target for the treatment of GC in the future.

miR-5195-3p Inhibits Proliferation and Invasion of Human Bladder Cancer Cells by Directly Targeting Oncogene KLF5.

miRNAs play a key role in the carcinogenesis of many cancers, including bladder cancer. In the current study, the role of miR-5195-3p, a quite recently discovered and poorly studied miRNA, in the proliferation and invasion of human bladder cancer cells was investigated. Our data displayed that, compared with healthy volunteers (control) and SU-HUC-1 normal human bladder epithelial cells, miR-5195-3p was sharply downregulated in bladder cancer patients and five human bladder cancer cell lines. The oligo miR-5195-3p mimic or miR-5195-3p antagomir was subsequently transfected into both T24 and BIU-87 bladder cancer cell lines. The miR-5195-3p mimic robustly increased the miR-5195-3p expression level and distinctly reduced the proliferation and invasion of T24 and BIU-87 cells. In contrast, the miR-5195-3p antagomir had an opposite effect on miR-5195-3p expression, cell proliferation, and invasion. Our data from bioinformatic and luciferase reporter gene assays identified that miR-5195-3p targeted the mRNA 3'-UTR of Krüppel-like factor 5 (KLF5), which is a proven proto-oncogene in bladder cancer. miR-5195-3p sharply reduced KLF5 expression and suppressed the expression or activation of its several downstream genes that are kinases improving cell survival or promoting cell cycle regulators, including ERK1/2, VEGFA, and cyclin D1. In conclusion, miR-5195-3p suppressed proliferation and invasion of human bladder cancer cells via suppression of KLF5.

Prognostic nutritional index predicts prognosis in patients with metastatic nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to investigate the prognostic value of Onodera's prognostic nutritional index (PNI) in patients with metastatic nasopharyngeal carcinoma (NPC). METHODS: A total of 187 patients with metastatic NPC treated with cisplatin-based chemotherapy were retrospectively reviewed. The PNI was calculated using the following formula: serum albumin level (gram per liter) +0.005× peripheral lymphocyte count (per cubic millimeter). A receiver operating characteristics curve for overall survival (OS) with the highest Youden index was determined to calculate the best cutoff value of PNI. The relationship between PNI and clinicopathological parameters was compared with the χ2 test. Survival analysis was applied to evaluate the predictive value of PNI. RESULTS: The median PNI in this study was 49.0 (ranging from 32.2 to 78.4). The best cutoff value of PNI for OS was 51.0 according to the receiver operating characteristics analysis. The median OS time was 13.0 months. The multivariate analysis indicated that the complete response (hazard ratio 0.681, 95% confidence interval 0.574-0.902; P=0.013) and PNI (hazard ratio 1.732, 95% confidence interval 1.216-2.892; P=0.005) were independent prognostic factors for OS in patients with metastatic NPC. CONCLUSION: This study revealed that PNI is a simple and effective predictor for overall survival in patients with metastatic NPC.

Endogenous IL-11 signaling is essential in Th2- and IL-13-induced inflammation and mucus production.

IL-11 and IL-11 receptor (R)alpha are induced by Th2 cytokines. However, the role(s) of endogenous IL-11 in antigen-induced Th2 inflammation has not been fully defined. We hypothesized that IL-11, signaling via IL-11Ralpha, plays an important role in aeroallergen-induced Th2 inflammation and mucus metaplasia. To test this hypothesis, we compared the responses induced by the aeroallergen ovalbumin (OVA) in wild-type (WT) and IL-11Ralpha-null mutant mice. We also generated and defined the effects of an antagonistic IL-11 mutein on pulmonary Th2 responses. Increased levels of IgE, eosinophilic tissue and bronchoalveolar lavage (BAL) inflammation, IL-13 production, and increased mucus production and secretion were noted in OVA-sensitized and -challenged WT mice. These responses were at least partially IL-11 dependent because each was decreased in mice with null mutations of IL-11Ralpha. Importantly, the administration of the IL-11 mutein to OVA-sensitized mice before aerosol antigen challenge also caused a significant decrease in OVA-induced inflammation, mucus responses, and IL-13 production. Intraperitoneal administration of the mutein to lung-specific IL-13-overexpressing transgenic mice also reduced BAL inflammation and airway mucus elaboration. These studies demonstrate that endogenous IL-11R signaling plays an important role in antigen-induced sensitization, eosinophilic inflammation, and airway mucus production. They also demonstrate that Th2 and IL-13 responses can be regulated by interventions that manipulate IL-11 signaling in the murine lung.

Lung-specific nuclear reprogramming is accompanied by heterokaryon formation and Y chromosome loss following bone marrow transplantation and secondary inflammation.

Cell fusion is one mechanism by which bone marrow-derived cells (BMDCs) take on the gene expression pattern of nonhematopoietic cells. This process occurs in a number of organs with postengraftment injury but has never been found in the lung. We performed bone marrow (BM) transplant in a murine model of lung inflammation to test whether transplanted BMDCs develop lung-specific gene expression by fusing with diseased pneumocytes. Mice lacking the lung-specific protein surfactant protein C (Sp-C) were lethally irradiated, transplanted with sex mismatched wild-type marrow, and sacrificed 6 months later. Nineteen/38 recipients exhibited Sp-C mRNA (RT-PCR) and/or protein (mean 0.95+/-1.18 Sp-C+ cells per 1000 type II pneumocytes by confocal microscopy). In male recipients of female BM, 65% of Sp-C + cells contained the Y chromosome, indicating their origin from fusion. Only 28% of Sp-C+ cells in female recipients of male BMDCs contained the Y chromosome, suggesting that 72% of Sp-C-expressing cells lost the Y chromosome. In the setting of post-transplant inflammation, pneumocyte-specific reprogramming of transplanted BMDCs predominantly derives from heterokaryon formation. This process does not reverse inflammation caused by Sp-C deficiency; nevertheless, further investigation may identify phenotypes benefiting from such an approach.

Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema.

Th1 inflammation and remodeling characterized by tissue destruction frequently coexist in human diseases. To further understand the mechanisms of these responses, we defined the role(s) of CCR5 in the pathogenesis of IFN-gamma-induced inflammation and remodeling in a murine emphysema model. IFN-gamma was a potent stimulator of the CCR5 ligands macrophage inflammatory protein-1alpha/CCL-3 (MIP-1alpha/CCL-3), MIP-1beta/CCL-4, and RANTES/CCL-5, among others. Antibody neutralization or null mutation of CCR5 decreased IFN-gamma-induced inflammation, DNA injury, apoptosis, and alveolar remodeling. These interventions decreased the expression of select chemokines, including CCR5 ligands and MMP-9, and increased levels of secretory leukocyte protease inhibitor. They also decreased the expression and/or activation of Fas, FasL, TNF, caspase-3, -8, and -9, Bid, and Bax. In accordance with these findings, cigarette smoke induced pulmonary inflammation, DNA injury, apoptosis, and emphysema via an IFN-gamma-dependent pathway(s), and a null mutation of CCR5 decreased these responses. These studies demonstrate that IFN-gamma is a potent stimulator of CC and CXC chemokines and highlight the importance of CCR5 in the pathogenesis of IFN-gamma-induced and cigarette smoke-induced inflammation, tissue remodeling, and emphysema. They also demonstrate that CCR5 is required for optimal IFN-gamma stimulation of its own ligands, other chemokines, MMPs, caspases, and cell death regulators and the inhibition of antiproteases.

Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury.

Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we characterized the expression of A1 and the oxygen susceptibility of WT and IL-11 Tg(+) mice with normal and null A1 loci. In WT mice, 100% O(2) caused TUNEL(+) cell death, induction and activation of intrinsic and mitochondrial-death pathways, and alveolar protein leak. Bcl-2 and Bcl-xl were also induced as an apparent protective response. A1 was induced in hyperoxia, and in A1-null mice, the toxic effects of hyperoxia were exaggerated, Bcl-2 and Bcl-xl were not induced, and premature death was seen. In contrast, IL-11 stimulated A1, diminished the toxic effects of hyperoxia, stimulated Bcl-2 and Bcl-xl, and enhanced murine survival in 100% O(2). In A1-null mice, IL-11-induced protection, survival advantage, and Bcl-2 and Bcl-xl induction were significantly decreased. VEGF also conferred protection via an A1-dependent mechanism. In vitro hyperoxia also stimulated A1, and A1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. A1 is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and Bcl-2 and Bcl-xl gene expression and a critical mediator of IL-11- and VEGF-induced cytoprotection.

IL-11 receptor alpha in the pathogenesis of IL-13-induced inflammation and remodeling.

IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation. In Th2-dominant inflammatory disorders such as asthma, IL-11 is simultaneously induced. However, the relationship(s) between IL-11 and IL-13 in these responses has not been defined, and the role(s) of IL-11 in the genesis of the tissue effects of IL-13 has not been evaluated. We hypothesized that IL-11, signaling via the IL-11Ralpha-gp130 receptor complex, plays a key role in IL-13-induced tissue responses. To test this hypothesis we compared the expression of IL-11, IL-11Ralpha, and gp130 in lungs from wild-type mice and transgenic mice in which IL-13 was overexpressed in a lung-specific fashion. We simultaneously characterized the effects of a null mutation of IL-11Ralpha on the tissue effects of transgenic IL-13. These studies demonstrate that IL-13 is a potent stimulator of IL-11 and IL-11Ralpha. They also demonstrate that IL-13 is a potent stimulator of inflammation, fibrosis, hyaluronic acid accumulation, myofibroblast accumulation, alveolar remodeling, mucus metaplasia, and respiratory failure and death in mice with wild-type IL-11Ralpha loci and that these alterations are ameliorated in the absence of IL-11Ralpha. Lastly, they provide insight into the mechanisms of these processes by demonstrating that IL-13 stimulates CC chemokines, matrix metalloproteinases, mucin genes, and gob-5 and stimulates and activates TGF-beta1 via IL-11Ralpha-dependent pathways. When viewed in combination, these studies demonstrate that IL-11Ralpha plays a key role in the pathogenesis of IL-13-induced inflammation and remodeling.

Pneumatic lithotripsy for ureterolithiasis: clinical analysis of 512 cases.

OBJECTIVE: To investigate the therapeutic effects of pneumatic lithotripsy (PL) through ureteroscope in the treatment of ureterolithiasis. METHOD: The clinical application of rigid ureteroscopy in 512 cases were retrospectively analyzed. RESULTS: Among the 512 cases, 486 had satisfactory therapeutic effects with the success rate of 94.9%. Failure of ureteroscope insertion occurred in 12 cases, leaving a success rate for the insertion of 97.7% (500/512). During the operations, ureteral stones in 14 cases failed to be eliminated, and the total success rate of PL reached 97.2% (486/500). CONCLUSION: The therapeutic effects of PL through ureteroscope were reliable and safe in the treatment of ureteral stones, with rapid postoperative recovery.

Pulmonary expression of leukemia inhibitory factor induces B cell hyperplasia and confers protection in hyperoxia.

Leukemia inhibitory factor (LIF) is produced by a large number of pulmonary cells in response to diverse stimuli. Exaggerated levels of LIF have also been detected in the adult respiratory distress syndrome and other disorders. The biologic effects of LIF in the lung, however, have not been elucidated. To define the respiratory effects of LIF, we generated transgenic mice in which human LIF was selectively targeted to the mature lung. In these mice, transgene activation caused an impressive increase in bronchoalveolar lavage (BAL) cellularity with a significant increase in BAL and tissue B lymphocytes. LIF also conferred protection in 100% O2 where it decreased alveolar-capillary protein leak and enhanced survival. This protective effect was associated with the induction of interleukin (IL)-6 mRNA and protein. LIF transgenic mice with a null mutation in IL-6 were more sensitive to the toxic effects of 100% O2 than LIF-transgenic animals with a wild-type IL-6 locus. These studies demonstrate that LIF induces B cell hyperplasia and confers protection in hyperoxic acute lung injury. They also demonstrate that LIF induces IL-6 and that the protective effects of LIF are mediated, in part, via this inductive event. LIF may be an important regulator of B cell-mediated responses and oxidant injury in the lung.

Transgenic modeling of interleukin-13 in the lung.

Interleukin (IL)-13 is a key cytokine in asthma pathogenesis. We used constitutive and inducible overexpression transgenic mice to characterize the mechanisms by which IL-13 causes phenotypic alterations in the lung. These studies demonstrated that chemokine receptor-2, transforming growth factor-beta(1), and IL-11 play an important role in the regulation of inflammation and remodeling in the IL-13-treated lung. The study results also demonstrated that IL-13 induces vascular endothelial growth factor, which causes bronchial circulation neovascularization in the murine airway. Last, it was demonstrated that IL-13 induces adenosine accumulation and that adenosine in turn stimulates IL-13 elaboration. These approaches validated in vivo genetic targets against which therapies can be directed to selectively regulate aspects of the IL-13 phenotype.