Perimidocarbene-Based Tetradentate Platinum(II) Complexes with an Unexpectedly Negligible 3MLCT Character.

Two novel six-membered perimidocarbene (PIC)-based tetradentate Pt(II) complexes were designed and successfully synthesized. Systematical experimental and theoretical studies suggest that the PIC moiety greatly affects the frontier orbitals, as well as the photophysical and excited-state properties of the Pt(II) complexes. PtYK2 has a broad emission spectrum peaking at 576 nm with a shoulder band at 620 nm, along with a full width at half-maximum (FWHM) value of 100.0 nm at 77 K in 2-MeTHF; however, the emission spectrum is slightly red-shifted with a dominant peak at 610 nm and a FWHM value of 125.0 nm at room temperature in a poly(methyl methacrylate) (PMMA) film. Time-dependent-density functional theory and natural transition orbital analyses reveal that PtYK2 has a 3LC (3πPIC* → πPIC)-dominated character with an unexpectedly negligible contribution of 3MLCT transition (0.68%) in the T1 state, which results in a broad emission spectrum and a relatively low quantum efficiency of 7.4% in the PMMA film.

UBE2C mediated radiotherapy resistance of head and neck squamous cell carcinoma by regulating oxidative-stress-relative apoptosis.

PURPOSE: Radiotherapy resistance is the main obstacle in the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). Increasing scientific opinions present that ubiquitin-conjugating enzyme E2C (UBE2C) might be a target gene acting as an oncogene. METHOD: TCGA database was used to analyze the expression of UBE2C in HNSCC patients, and the relationship between UBE2C expression and prognosis. Western blot and RT-PCR were used to assess UBE2C expression before and after radiation. Then, cell viability experiment and colony formation were used to evaluate proliferation after 2 Gy radiation. Cell viability experiment, migration, and invasion were evaluated in the condition of UBE2C knock-down. Western blot and RT-PCR were used to assess the expression of apoptosis and ROS relative gene expression. Then, the xenograft model was used to evaluate the efficacy of radiation combined with UBE2C suppression. RESULT: The expression of UBE2C was high in tumors of patients with HNSCC and relatives with poor prognoses. Si-UBE2C cells showed proliferation inhibited and apoptosis enhanced after radiation. Furthermore, the mechanism of UBE2C in HNSCC radioresistance was explored. We performed RT-PCR to find the 4-HNE, which increases oxidative-stress-relative apoptosis in Si-UBE2C cells after radiation. CONCLUSIONS: Through the RT-PCR, WB, cell viability experiment, migration, invasion, and in vivo experiment, UBE2C was confirmed to downregulate oxidative-stress-relative apoptosis induced by radiation and promote the development of malignant tumor cells.

Novel loop neurorrhaphy technique to preserve lower lip sensate in mandibular reconstruction using an innervated vascularized iliac bone flap.

BACKGROUND: This study aimed to introduce a novel loop neurorrhaphy technique using an innervated vascularized iliac bone flap (VIBF) with vascularized ilioinguinal nerve (IIN) to reconstruct the inferior alveolar nerve (IAN) and preserve lower lip sensation simultaneously with mandibular reconstruction. METHODS: This study prospectively included patients who underwent mandibular reconstruction using VIBF from May 2018 to April 2020. Subjects were allocated into two groups: (1) Group I; innervated VIBF with loop neurorrhaphy (IIN doubly anastomosed with IAN and mental nerve), (2) Group II (control); conventional VIBF. Evaluation was done with operative time, intraoperative indocyanine green (ICG), lower lip sensory assessment (two-point discrimination [TPD] test and current perception threshold [CPT]), and drooling. RESULTS: Twelve patients were included; 6 in each group, (7 males and 5 females), age ranging from 18 to 57 years (average: 36.75 years). In all cases, intraoperative perfusion of IIN was confirmed by ICG. Group I showed a statistically significant more flap harvesting time compared with group II (mean difference, 5.67 min; P = 0.0091). There was a significant difference in sensory recovery favoring group I (P < 0.05). The TPD results in group I showed an average of 9.8 ± 6.9 mm and 6.2 ± 5.7 mm on operated and non-operated sides, while Group II showed a poor sensory recovery, and the TPD showed an average of 24.6 ± 6.7 mm and 8.4 ± 2.3 mm on operated and non-operated sides. The CPT results showed a significant difference between both groups. In Group I, the extent of drooling was 3.16 ± 0.75, while in Group II, the score was 1.6 ± 0.81, revealing a significant difference favoring Group I. CONCLUSIONS: Concurrent mandibular reconstruction using VIBF and loop neurorrhaphy with vascularized IIN to reconstruct IAN successfully restore lower jaw form and preserve lip sensation.

Stimulator of interferon response cGAMP interactor overcomes ERBB2-mediated apatinib resistance in head and neck squamous cell carcinoma.

PURPOSE: Apatinib resistance is the main obstacle to the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate the function of Erb-B2 receptor tyrosine kinase 2 (ERBB2) and stimulator of interferon response cGAMP interactor (STING) in apatinib resistance in HNSCC. METHOD: The Cancer Genome Atlas database of HNSCC was used to analyze the relationship between vascular endothelial growth factor receptor 2 (VEGFR2) expression and prognosis. An apatinib resistant (AR) HNSCC cell line was constructed based on the CAL27 cell line. RNA sequencing was performed to explore the differentially expressed mRNAs. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were used to evaluate the expression and phosphorylation level VEGFR2, ERBB2, STING, and related proteins. Apatinib resistance was evaluated by colony formation and cell viability assays. A mouse subcutaneous tumor formation model was established to evaluate the efficiency of combination treatment and vascularization was evaluated by assessing CD31 immunofluorescence. RESULT: The expression of VEGFR2 was high in tumor of patients with HNSCC. Western blotting and qRT-PCR revealed that in AR cells, ERBB2 expression was high, whereas the expression of STING was low. Targeted treatment of ERBB2 using lapatinib could attenuate apatinib resistance. Further research confirmed that overexpressing STING could decrease ERBB2 expression. CONCLUSION: STING could sensitize AR cells to apatinib by decreasing ERBB2 expression. The combination of lapatinib or a STING agonist with apatinib ameliorated acquired apatinib resistance in a synergistic manner.

The application of chimeric deep circumflex iliac artery perforator flap for oromandibular reconstruction: A case report.

RATIONALE: The free fibular flap is considered the gold standard, particularly for a mandibular defect combined with a significant soft tissue defect. However, the fibular flap has the disadvantages of a lack of height for postoperative dental restoration and donor site skin graft if the skin paddle is wider than 5 cm. The larger bone and soft tissue defects tend to be reconstructed using either a scapula or a combination of iliac artery and radial free flap. Few cases involving reconstruction using chimeric deep circumflex iliac artery perforator flap (DCIAPF) for mandibular defect combined with more significant soft tissue defects have been reported due to perforator variations. We successfully performed oromandibular reconstruction using chimeric DCIAPF. PATIENT CONCERNS: A 56-year-old male patient was admitted due to "constant pain in the gradually enlarged right lower gingival mass since the previous four months." The patient had no other obvious symptoms, and no history of diabetes or hypertension was reported. The patient reported long-term smoking and drinking habits. DIAGNOSES: Computed tomography (CT) revealed a neoplasm in the right buccal space, which is primarily considered a malignancy. The pathological results of a gingival mass biopsy presented squamous cell carcinoma. INTERVENTIONS: No operative contraindications were confirmed after regular tests and examinations were undertaken. The patient underwent a primary extent resection of a 6-cm-long mandible, including mass and suprascapulohyoid neck dissection. The oromandibular defects were then reconstructed with chimeric DCIAPF, simultaneously using the iliac crest bone flap to repair the mandibular lateral segment defect and the skin paddle to repair the intraoral soft tissue defect of 5 × 10 cm. OUTCOMES: The total operating time was five and half hours and blood loss was approximately 500 ml. The operation was successful, with no infections or flap loss. Six months postoperatively, CT showed that the iliac crest bone had connected to the alveolar bone of the mandible. The height of the iliac crest bone was sufficient for postoperative dental restoration. The patient healed without obvious complications and no tumor recurrence. LESSONS: Chimeric DCIAPF is an excellent option for mandibular angle or body segment defects combined with significant soft tissue defects.

Research progress on posttreatment trismus in malignant head and neck tumors / 口腔疾病防治

@#Malignant tumors in the head and neck seriously threaten the physical and mental health of patients. After treatment, they may cause many complications, such as facial deformity, difficulties with chewing, dysphagia and asaphia. Among them, trismus (restricted mouth opening) is one of the most common complications after treatment of malignant oral-maxillofacial tumors. In severe cases, patients may even suffer from trismus and eating difficulties, finally leading to malnutrition and even cachexia. Therefore, it not only affects the quality of life of patients and even endangers their lives but also brings heavy social and economic burdens. How to effectively prevent and treat posttreatment trismus is a clinical problem that is easily ignored by head and neck surgeons and urgently needs to be solved. The results of a literature review showed that trismus may be related to the tumor clinical stage, tumor site, treatment used, radiotherapy site, radiotherapy dose, radiotherapy type, and other factors. The incidence of trismus tends to be significant 6 months after treatment. Without early intervention, the resulting dysfunction may become more severe. Current studies have shown that the prevention and treatment of restricted mouth opening is based on controlling the progress of restricted mouth opening and restoring function. Exercise intervention for trismus can significantly improve the restricted mouth opening of patients with malignant head and neck tumors after treatment.

CuGeO3 Nanoparticles: An Efficient Photothermal Theragnosis Agent for CT Imaging-Guided Photothermal Therapy of Cancers.

The photothermal agents have been widely developed due to the minimally invasive treatment for targeted tumor photothermal therapy, which is considered to have great potential for antitumor bioapplications. The development of multifunctional photothermal agents is extremely challenging. This work presents a novel photothermal theragnosis agent, i.e., CuGeO3 nanoparticles (CGO NPs), showing intense absorption in the near-infrared (NIR) window and excellent ability of CT imaging. Due to the strong NIR absorption, CGO NPs exhibit excellent photothermal effect with a photothermal conversion efficiency of 59.4%. Moreover, because of the high X-ray attenuation coefficient of germanium, the CGO NPs have a great potential of CT imaging diagnosis in clinical application. Additionally, the CGO NPs show negligible cytotoxicity in vitro and in vivo, indicating that it can be served as an outstanding contrast and anticancer agent in a biosafe way. Our work opens the way for the development of bimetallic copper-based oxides used in photothermal diagnostic agents for cancer treatment.

A prognostic long non-coding RNA-associated competing endogenous RNA network in head and neck squamous cell carcinoma.

BACKGROUND: This study aimed to develop multi-RNA-based models using a competing endogenous RNA (ceRNA) regulatory network to provide survival risk prediction in head and neck squamous cell carcinoma (HNSCC). METHODS: All long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA expression data and clinicopathological features related to HNSCC were derived from The Cancer Genome Atlas. Differentially expressed RNAs were calculated using R. Prognostic factors were identified using univariate Cox regression analysis. Functional analysis was performed using GO, KEGG pathways, and PPI network. Based on the results, we derived a risk signature and compared high- and low-risk subgroups using LASSO regression analysis. Survival analysis and the relationship between risk signature and clinicopathological features were performed using log-rank tests and Cox regression analysis. A ceRNA regulatory network was constructed, and prognostic lncRNAs and miRNA expression levels were validated in vitro and in vivo. RESULTS: A list of 207 lncRNAs, 18 miRNAs and 362 mRNAs related to overall survival was established. Five lncRNAs (HOTTIP, LINC00460, RMST, SFTA1P, and TM4SF19-AS1), one miRNA (hsa-miR-206), and one mRNA (STC2) were used to construct the ceRNA network. Three prognostic models contained 13 lncRNAs, eight miRNAs, and 17 mRNAs, which correlated with the patient status, disease-free survival (DFS), stage, grade, T stage, N stage, TP53 mutation status, angiolymphatic invasion, HPV status, and extracapsular spread. KEGG pathway analysis revealed significant enrichment of "Transcriptional misregulation in cancer" and "Neuroactive ligand-receptor interaction." In addition, HOTTIP, LINC00460, miR-206 and STC2 were validated in GTEx data, GEO microarrays and six HNSCC cell lines. CONCLUSIONS: Our findings clarify the interaction of ceRNA regulatory networks and crucial clinicopathological features. These results show that prognostic biomarkers can be identified by constructing multi-RNA-based prognostic models, which can be used for survival risk prediction in patients with HNSCC.

Effect of m6A RNA Methylation Regulators on Malignant Progression and Prognosis in Renal Clear Cell Carcinoma.

Objectives: This study aims to explore the roles of 13 m6A RNA methylation regulators in clear cell renal cell carcinoma (ccRCC), and identify a risk signature and prognostic values of m6A RNA methylation regulators in ccRCC. Materials and Methods: RNA sequence data of ccRCC was obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed of 13 m6A RNA methylation regulators in ccRCC stratified by different clinicopathological characteristics were unveiled using "limma" package in R version 3.6.0. Cox regression and LASSO analyses were conducted to identify the powerful independent prognostic factors in ccRCC associated with overall survival (OS). Protein-protein interaction (PPI) network and correlation analyses of the 13 m6A RNA methylation regulators were performed using "STRING" and R package, respectively. Principal component analysis (PCA) was also done using R. In addition, gene ontology (GO), GSEA and Kyoto Encyclopedia of Genes and Genomes pathways were used to functionally annotate the differentially expressed genes in different subgroups. Results: Most of the 13 m6A RNA methylation regulators are differentially expressed in ccRCC tissue samples stratified by different clinicopathological characteristics in 537 patients. Next, a risk signature for predicting prognosis of ccRCC patients, was established based on two powerful independent prognostic m6A RNA methylation regulators (METTL14 and METTL3). Then, two subgroups (cluster1 and 2) were identified by consensus clustering to the two powerful independent factors and the cluster1 had a poorer prognosis than cluster2. Furthermore, the genes in cluster1 were significantly enriched in cancer-related pathways, biological process, and hallmarks, including "cell adhesion molecules (CAMs)," "leukocyte migration," "Wnt/ß-catenin signaling," and so on. Conclusion: M6A RNA methylation regulators play important roles in the initiation and progression of ccRCC and provide a novel sight to understand m6A RNA modification in ccRCC.

[Simultaneous innervation revitalizes bone marrow mesenchymal stem cells from postoperative iliac grafts].

PURPOSE：To compare the osteogenic potential of bone marrow mesenchymal stem cells (BMMSCs) from innervated iliac graft bone flap and traditional one for reconstructing mandibular defects. METHODS：Graft bone marrow samples were harvested 1 year after free vascularized iliac reconstruction of mandibular defects, with or without innervation through simultaneous nerve anastomosis. BMMSCs were isolated and cultured in vitro. Colony forming units-fibrosis observation, Brdu incorporation assay, population doubling, Alizarin red staining for in vitro calcified nodule formation and in vivo assay of subcutaneous osteogenesis in nude mice were used to detect BMMSCs proliferation, self-renewal and osteogenic differentiation capabilities, respectively. SPSS 24.0 software package was used for statistical analysis. RESULTS：Colony formation, proliferation, population doubling and osteogenic differentiation abilities of BMMSCs from innervated group were significantly higher than those from non-innervated group（P<0.05）. CONCLUSIONS：Simultaneous innervation of free vascularized iliac during reconstruction of mandibular defects may maintain self-renewal and osteogenic differentiation potentials of BMMSCs in graft bones, thereby maintaining bone homeostasis and reducing postoperative graft bone resorption.

Identification and analysis of long non-coding RNA related miRNA sponge regulatory network in bladder urothelial carcinoma.

BACKGROUND: The aim of this study was to investigate the regulatory network of lncRNAs as competing endogenous RNAs (ceRNA) in bladder urothelial carcinoma (BUC) based on gene expression data derived from The Cancer Genome Atlas (TCGA). MATERIALS AND METHODS: RNA sequence profiles and clinical information from 414 BUC tissues and 19 non-tumor adjacent tissues were downloaded from TCGA. Differentially expressed RNAs derived from BUC and non-tumor adjacent samples were identified using the R package "edgeR". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the "clusterProfiler" package. Gene ontology and protein-protein interaction (PPI) networks were analyzed for the differentially expressed mRNAs using the "STRING" database. The network for the dysregulated lncRNA associated ceRNAs was then constructed for BUC using miRcode, miRTarBase, miRDB, and TargetScan. Cox regression analysis was performed to identify independent prognostic RNAs associated with BUC overall survival (OS). Survival analysis for the independent prognostic RNAs within the ceRNA network was calculated using Kaplan-Meier curves. RESULTS: Based on our analysis, a total of 666, 1819 and 157 differentially expressed lncRNAs, mRNAs and miRNAs were identified respectively. The ceRNA network was then constructed and contained 59 lncRNAs, 23 DEmiRNAs, and 52 DEmRNAs. In total, 5 lncRNAs (HCG22, ADAMTS9-AS1, ADAMTS9-AS2, AC078778.1, and AC112721.1), 2 miRNAs (hsa-mir-145 and hsa-mir-141) and 6 mRNAs (ZEB1, TMEM100, MAP1B, DUSP2, JUN, and AIFM3) were found to be related to OS. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) and 4 mRNA (DUSP2, JUN, MAP1B, and TMEM100) were validated using GEPIA. Thirty key hub genes were identified using the ranking method of degree. KEGG analysis demonstrated that the majority of the DEmRNAs were involved in pathways associated with cancer. CONCLUSION: Our findings provide an understanding of the important role of lncRNA-related ceRNAs in BUC. Additional experimental and clinical validations are required to support our findings.

Treatment of adenoid cystic carcinoma of the mobile tongue with anterolateral thigh flap reconstruction: A case report.

RATIONALE: Adenoid cystic carcinoma (ACC) is an infrequent malignant neoplasm of the salivary glands. The clinical and pathological characteristics include slow growth, perineural invasion, and local recurrence. ACC of the mobile tongue is rarely reported in the literature. PATIENT CONCERNS: We describe a case of a 43-year-old man patient with numbness and growth in the tongue for 1 month duration. The patient reported a long-term smoking and drinking habit. DIAGNOSES: A biopsy was carried out and histopathological analysis confirmed as diagnosis of adenoid cystic carcinoma. Computed tomography (CT) of the head and neck enhanced scanning revealed an ill-defined high density mass with altered enhanced signal entities involving the anterior 2/3rd of the tongue. INTERVENTIONS: The patient was treated with surgery and adjuvant radiotherapy. Incision was placed over the anteriorly till 2/3rd of tongue and then the femoral anterolateral free flap was used to repair and reconstruct the defect of tongue. OUTCOME: The patient is currently under a postsurgical 29-month regular follow-up, showing good swallowing and speaking function without any recurrence and metastasis. LESSONS: This case report suggests that surgery and adjuvant radiotherapy are suitable procedures for patients with resectable ACC of the mobile tongue.

Construction and comprehensive analysis of dysregulated long non-coding RNA-associated competing endogenous RNA network in clear cell renal cell carcinoma.

OBJECTIVE: This study aimed to assess the long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in clear cell renal cell carcinoma (ccRCC) by gene expression analyses. MATERIALS AND METHODS: LncRNA, miRNA, and mRNA expression profiles in ccRCC were obtained from The Cancer Genome Atlas. Differentially expressed lncRNAs, mRNAs (cut-off: |log 2 [fold change, FC])| > 2.0 and adjusted P < 0.01) and miRNAs (|log 2FC| > 1.5 and adjusted P < 0.01) were unveiled using R. Cox regression analysis was performed to identify prognostic factors of ccRCC related to overall survival (OS). A protein-protein interaction (PPI) network was constructed for differentially expressed mRNAs (DEmRNAs) by Search Tool for the Retrieval of Interacting Genes (STRING). Key hub genes were screened from top 300 DEmRNAs. LncRNA-miRNA and miRNA-mRNA regulatory network were constructed and combined into the competing endogenous RNA regulatory network. Gene ontology biological terms were screened by STRING; Kyoto Encyclopedia of Genes and Genomes pathways were identified using the "clusterProfiler" package in R. RESULTS: A total of 2331, 1517, and 83 DEmRNAs, lncRNAs, and miRNAs were identified, respectively. Eleven lncRNAs (AC016773.1, HOTTIP, LINC00460, NALCN-AS1, PVT1, TRIM36-IT1, WT1-AS, COL18A1-AS1, LINC00443, LINC00472, and TCL6), three miRNAs (hsa-mir-21, hsa-mir-144, and hsa-mir-155), and three mRNAs (COL4A4, NOD2, and GOLGA8B) were associated with OS. Specifically, four lncRNAs (PVT1, LINC00472, TCL6, and WT1-AS1) and one mRNA (Collagen Type IV Alpha 4 Chain) were verified as independent prognostic factors by Gene Expression Profiling Interactive Analysis. Eleven key hub genes were obtained by PPI analysis. "Cell adhesion molecules (CAMs)," "chemical carcinogenesis," and "cytokine-cytokine receptor interaction" were significantly enriched in the network. CONCLUSION: The findings clarify the pathogenesis of ccRCC and might provide potential therapeutic targets.

Collagen/ß-TCP nerve guidance conduits promote facial nerve regeneration in mini-swine and the underlying biological mechanism: A pilot in vivo study.

This study aimed to evaluate the efficiency of new nerve guidance conduits (NGCs) in bridging facial nerve gaps, and investigate the underlying biological mechanisms implicated in the regeneration process. A collagen/ß-TCP conduit was prepared and applied to a facial nerve gap in a mini-swine model. Functional recovery and axonal regeneration were further evaluated by electrophysiological and histological examinations at 3 months after surgery. Furthermore, the global transcriptomic profiles of regenerated and normal tissues were analyzed by gene microarray to identify the differentially expressed genes at day three and seven, postoperatively. Subsequently, associated biological processes were analyzed by gene ontology (GO) enrichment analysis. The electrophysiological examination and morphological analysis revealed that significant nerve regeneration effects were achieved in the Col/ß-TCP group (p < 0.05). Transcriptional analysis revealed that at day three post-surgery, the majority of overexpressed genes were associated with inflammatory, immune and stimuli response, accompanied by angiogenesis, while at day seven, the majority of overexpressed genes were associated with cell, tissue and organ regeneration and development, synaptic transmission, neurogenesis, and neuronal differentiation, as well as the WNT, MAPK/ERK, and JAK/STAT signaling pathways. In conclusion, the present results suggest that collagen/ß-TCP NGCs provide a promising tubular micro-environment for nerve regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1122-1131, 2019.

Biomimetic intrafibrillar mineralized collagen promotes bone regeneration via activation of the Wnt signaling pathway.

PURPOSE: The purpose of this study was to assess the effects of biomimetic intrafibrillar mineralized collagen (IMC) bone scaffold materials on bone regeneration and the underlying biological mechanisms. MATERIALS AND METHODS: A critical-sized bone defect in the rat femur was created; then IMC, extrafibrillar mineralized collagen, and nano-hydroxyapatite bone scaffold materials were grafted into the defect. Ten weeks after implantation, micro-computed tomography and histology were applied to evaluate the bone regeneration. Furthermore, microarray technology was applied for transcriptional profile analysis at two postoperative time points (7 and 14 days). Subsequently, the critical genes involved in bone regeneration identified by transcriptional analysis were verified both in vivo through immunohistochemical analysis and in vitro by quantitative real-time transcription polymerase chain reaction evaluation. RESULTS: Significantly increased new bone formation was found in the IMC group based on micro-computed tomography and histological evaluation (P<0.05). Transcriptional analysis revealed that the early process of IMC-guided bone regeneration involves the overexpression of genes mainly associated with inflammation, immune response, skeletal development, angiogenesis, neurogenesis, and the Wnt signaling pathway. The roles of the Wnt signaling pathway-related factors Wnt5a, ß-catenin, and Axin2 were further confirmed both in vivo and in vitro. CONCLUSION: The IMC bone scaffold materials significantly enhanced bone regeneration via activation of the Wnt signaling pathway.

The Effect of Local Anesthetic Infiltration Around Nephrostomy Tract on Postoperative Pain Control after Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the safety and efficacy of local anesthetic infiltration around nephrostomy tract on postoperative pain control after percutaneous nephrolithotomy. METHODS: This systematic review was performed based on randomized clinic trials about local anesthetic infiltration around nephrostomy tract on postoperative pain control. The weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. RESULTS: Our results showed that the consumption of analgesic was less in the experimental group than in the control group (WMD -25.32, 95% CI -48.09 to -2.55, p = 0.003). There was no significant difference between the mean Visual Analog Scale (VAS) in the experimental group than the control group after 6 h while significantly lower after 24 h. The time of first analgesic demand was significantly longer in the experimental group (WMD 2.19, 95% CI 0.98-3.41). There was no significant difference between 2 groups in terms of operation time, hemoglobin (Hb) alteration, and hospital stay. CONCLUSION: Local anesthetic infiltration around nephrostomy tract had similar efficacy in the control group in terms of operation time, Hb alteration, and hospital stay, but offers some potential advantages in terms of analgesia requirement, the time of first analgesic demand, and VAS-24 h. However, good quality and large studies with long-term follow-up are warranted for further research.

Pleiotropic effects of survivin in vascular endothelial cells.

OBJECTIVE: To assess the effects of survivin (SVV)in vascular endothelial cells. METHODS: In this study, we applied a gain-of-function approach and ectopically expressed SVV in rat aortic endothelial cells (RAECs) using a SVV-expressing adenovirus. The resulting SVV expression on the steady-state mRNA and protein level in RAECs was determined by reverse transcription quantitative PCR and Western blot, respectively. Cell viability, apoptosis, and migration were assessed in vitro by CCK-8 assay, flow cytometry, and transwell assay, respectively. The effect of SVV on in vivo angiogenesis was evaluated by immunohistochemistry in nude mice. Non-infected RAECs and those infected with GFP-expressing control adenovirus were used as controls. RESULTS: Compared to non-infected or control adenovirus-infected RAECs in vitro, SVV-expressing cells had increased viability and migratory capability, but reduced apoptosis. In vivo, SVV-expressing RAECs were associated with a higher level of angiogenesis. CONCLUSION: SVV is a positive regulator of endothelial cell survival and migration, and thus, stabilizes endothelial cells and stimulates angiogenesis.

GdCl3 suppresses the malignant potential of hepatocellular carcinoma by inhibiting the expression of CD206 in tumor­associated macrophages.

In the present study, we aimed to ascertain whether there is a correlation between CD206 expression in tumor associated-macrophages (TAMs) and the prognosis of primary hepatocellular carcinomas (HCC) and we investigated the effect of GdCl3 on HCC. The expression of CD206 in HCC tumor tissues and peri-carcinoma tissues was measured using an array for liver tissues. The effects of GdCl3 on CD206 expression were examined in stimulated RAW264.7 cells. Target gene expression was evaluated by RT-PCR, western blotting and immunohistochemistry. The transwell system was used to assess the invasiveness of HCC cells. Finally, we established a mouse model for HCC using N-nitrosodiethylamine (DEN) to determine the effect of GdCl3 on HCC. Liver tissue array analysis revealed that CD206 was highly expressed in the HCC tissues compared to the level in peri-carcinoma tissue. We found that GdCl3 suppressed the expression of CD206 in the M2 macrophage phenotype of stimulated RAW264.7 cells with an IC10 value of 0.07 µg/µl. In addition, GdCl3 also induced cell apoptosis in the RAW264.7 cells. Addition of GdCl3 into the culture medium of RAW264.7 cells markedly reduced the invasive ability of Hepa1-6 cells compared to the control cells. Accordingly, GdCl3 treatment increased the expression of the epithelial-mesenchymal transition (EMT)-related protein E-cadherin while expression of N-cadherin, TWIST and Snail was reduced in IL-4-stimulated cells. Moreover, GdCl3 treatment inhibited HCC progression in DEN-induced HCC mice, possibly by downregulating CD206. Our findings indicate that CD206 is a potential biomarker for predicting HCC prognosis and that GdCl3 suppresses HCC progression by downregulating the expression of CD206 in TAMs.

The use of adjunctive hemostatic agents in tubeless percutaneous nephrolithotomy: a meta-analysis.

The purpose of the study was to systematically review and assess the safety and efficacy of hemostatic agents in tubeless percutaneous nephrolithotomy. Original studies on the use of hemostatic agents in tubeless percutaneous nephrolithotomy (PCNL) from January 2001 to March 2014 were searched in Ovid, Science Direct, Pubmed, and Embase by two independent reviewers. A drop in hemoglobin (Hb), analgesic requirements, length of hospital stay, and necessity for blood transfusions were compared using Review Manager 5.2. The methods were done according to the Cochrane Handbook for interventional systematic reviews and written based on the PRISMA Statement. Seven studies involving 351 patients met the inclusion criteria for the meta-analysis. The baseline characteristics were comparable in all of the studies. The results showed that the length of hospital stay was less in the experimental group than in the control group (P < 0.05). There were no significant statistical differences in terms of a drop in Hb, analgesic requirements, and the necessity for a blood transfusion between the two groups (P > 0.05). The meta-analysis indicated that the hemostatic agents in tubeless PCNL were not expected to be unsafe or mandatory, but that they were expected to be expensive. We concluded that hemostatic agents might not be necessary in tubeless PCNL.