Safety and efficacy of percutaneous electrocoagulation haemostasis in the treatment of grade IV haemorrhagic cystitis after allogeneic haematopoietic stem cell transplantation in children: a retrospective analysis.

BACKGROUND: To investigate the efficacy and safety of endoscopic electrocoagulation haemostasis via a percutaneous transhepatic approach for the treatment of grade IV haemorrhagic cystitis (HC) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 14 children with severe HC, who were admitted to Hebei Yanda Hospital between July 2017 and January 2020, were analysed retrospectively. There were nine males and five females, with an average age of 8.6 years (range: 3 to 13 years). After an average of 39.6 (7 to 96) days of conservative treatment in the hospital's haematology department, the bladders of all patients were filled with blood clots. A small 2-cm incision was made in the suprapubic area to enter the bladder and quickly clear the blood clots, and a percutaneous transhepatic approach to electrocoagulation and haemostasis was performed. RESULTS: In the 14 children, a total of 16 operations were performed, with an average operation time of 97.1 (31 to 150) min, an average blood clot of 128.1 (80 to 460) mL and an average intraoperative blood loss of 31.9 (20 to 50) mL. There were three cases of postoperative bladder spasm remission after conservative treatment. During the follow-up period of 1 to 31 months, one patient improved after one operation, 11 patients were cured after one operation, and two patients were cured after recurrent haemostasis by secondary electrocoagulation, four of whom died of postoperative non-surgical blood-related diseases and severe lung infections. CONCLUSION: Percutaneous electrocoagulation haemostasis can quickly remove blood clots in the bladders of children after allo-HSCT with grade IV HC. It is a safe and effective minimally invasive treatment.

Nickel-Catalyzed Three-Component Tandem Radical Cyclization 1,5-Difunctionalization of 1,3-Enynes and Alkyl Bromide.

A nickel-catalyzed three-component tandem radical cyclization reaction of aryl bromides with 1,3-enynes and aryl boric acids to construct γ-lactam-substituted allene derivatives has been described. This protocol provides lactam alkyl radicals through the free radical cyclization process, which can be effectively used to participate in the subsequent multicomponent coupling reaction so that 1,3-enynes could directly convert into corresponding poly-substituted allene compounds. In addition, this efficient method enjoys a broad substrate scope and provides a series of 1,5-difunctionalized allenes in a one-pot reaction.

MicroRNA-146a inhibits autophagy to maintain the intracellular survival of Burkholderia pseudomallei by targeting LIPA.

Burkholderia pseudomallei is the etiological agent of melioidosis, which is an emerging infectious disease endemic to many tropical regions. Autophagy is an intrinsic cellular process that degrades cytoplasmic components and plays an important role in protecting the host against pathogens. Like many intracellular pathogens, B. pseudomallei can evade the autophagy-dependent cellular clearance. However, the underlying mechanism remains unclear. In this study, we applied a combination of multiple assays to monitor autophagy processes and found that B. pseudomallei induced an incomplete autophagic flux and eliminate autophagy clearance in macrophages by blocking autophagosome-lysosome fusion. Based on a high-throughput microarray screening, we found that LIPA (lysosomal acid LIPAse A) was downregulated during B. pseudomallei infection. MiR-146a was then identified to be specifically upregulated upon infection with B. pseudomallei and further regulated LIPA expression by interacting with 3'UTR of LIPA. Furthermore, overexpression of miR-146a contributed to the defect of autophagic flux caused by B. pseudomallei and was beneficial for the survival of B. pseudomallei in macrophages. Therefore, our findings suggest that miR-146a inhibits autophagy via posttranscriptional suppression of LIPA expression to maintain B. pseudomallei survival in macrophages.

Overexpression of ß-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Abnormal expression of ß-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of ß-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of ß-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with ß-catenin knockin and knockdown. In this study, we found that higher expression level of ß-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of ß-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of ß-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism of ß-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of ß-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3ß, C-myc, Bcl-2, P-gp, and MRP-1 were involved in ß-catenin-mediated drug resistance. Our findings indicate that the Wnt/ß-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.

Mandibular reconstruction assisted by preoperative simulation and accurate transferring templates: preliminary report of clinical application.

PURPOSE: This study investigated the application of a computer-aided design and manufacturing technique of defining tumor resection, fibula cutting, and positioning by surgical templates in mandibular reconstructive surgery. MATERIALS AND METHODS: Four patients who required mandibulectomy and simultaneous reconstruction were enrolled in this study. Preoperative surgical simulation was performed. The surgical templates that defined tumor resection, fibula cutting, and positioning were designed and fabricated. RESULTS: The surgeries were performed to the preoperative plan. All flaps survived. Superimposition of the postoperative image and the preoperative plan showed a satisfactory surgical accuracy. CONCLUSIONS: This method of defining tumor resection, fibula cutting, and positioning by surgical templates was accurate enough for mandibular reconstructive surgery.

Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands.

BACKGROUND: The relationship between autophagy and chemotherapy in cancer has been studied a lot recent years. However, there is currently no study on the role of autophagy in chemotherapy of adenoid cystic carcinoma (ACC) of human salivary glands. We hypothesized that autophagy plays a protective role for human salivary gland ACC cells during chemotherapy, diminishes the effect of treatment, and ultimately results in poor sensitivity to chemotherapy. MATERIALS AND METHODS: After inhibition of autophagy by 5 mM 3-methyladenine (3MA), 20 µM Chloroquine (CQ), or Beclin-1 shRNA, we examined the sensitivity of human salivary gland ACC cells to different concentrations of cis-diamminedichloroplatinum (CDDP) using MTT assay. Also, levels of autophagy in ACC cells treated by CDDP were assessed by western blot, GFP-LC3 fluorescence and transmission electron microscopy (TEM). RESULTS: Inhibition of autophagy induced by 3MA, CQ, or Beclin-1 shRNA could all enhance human salivary gland ACC cell death treated by CDDP. And, levels of autophagy in these cells showed a significant increase after treated by CDDP. CONCLUSION: Autophagy played a protective role for human salivary gland ACC cells during CDDP chemotherapy. Inhibition of autophagy in these cells could enhance cisplatin cytotoxicity-effects. These findings indicate a novel and promising way to reduce chemotherapy resistance and improve treatment outcome in human salivary gland ACC.

Suppression of tongue squamous cell carcinoma growth by inhibition of Jagged1 in vitro and in vivo.

BACKGROUND: The changes in Notch signaling are closely related to the occurrence and development of many cancers. We have investigated Notch signaling receptor and its ligand expressions in TSCC cell lines, tissues and its significance. We clarified Notch signaling pathway in TSCC and its mechanism. We regulated Notch signaling pathway of tumor cells, thereby inhibiting tumor cell proliferation and differentiation. METHODS: We detected Jagged1 protein and mRNA expression levels in specimens (tongue cancer and adjacent tissues) from 74 patients with tongue cancer and in TSCC cell line. The Jagged1-targeted lentiviral vector RNAi system was constructed, and its suppressive effects on the proliferation and invasion of tongue carcinoma cells in in vivo and ex vivo were determined. RESULTS: Jagged1 was expressed in tongue squamous cell cancer tissues and cell line, but there were differences in its expression. Jagged1 was knocked down and the tumor growth was inhibited accompanying cell cycle changes. Animal studies also showed that the tumor growth was inhibited. CONCLUSIONS: Jagged1 may be involved in the differentiation and proliferation of tongue cancer. Targeting Jagged1 RNA interference lentiviral vector can effectively lower Jagged1 mRNA and protein expression levels of Tca8113 cells, thereby preventing the proliferation of TSCC cells. Jagged1 is expected to be a promising new target for curing tongue cancer. In-depth study of the interaction between Jagged1 and other molecules of Notch signaling pathway in the process of carcinogenesis has important theoretical guidance and clinical significance in revealing the mechanism of Jagged1 and its application in the therapy for tongue cancer.

Mandible reconstruction assisted by preoperative virtual surgical simulation.

OBJECTIVE: In this study, we evaluated the clinical efficacy of mandible reconstruction with preoperative virtual planning, which focused on esthetics and occlusion. STUDY DESIGN: A series of 9 patients were enrolled prospectively to undergo mandibulectomy and simultaneous reconstruction. Preoperative spiral CT scans of the maxillofacial region and the fibula region were performed. Virtual surgery of tumor resection and fibula reconstruction was performed in the Mimics platform. The reconstructed mandible models were fabricated with CAD/CAM technique. The reconstruction plate and the positioning template were accommodated to the stereolithographic model as the surgical template. RESULTS: Surgery was performed accurately according to the templates. All the fibula flaps survived. The appearance and occlusion of the patients were satisfactory. CONCLUSIONS: With preoperative virtual planning, the spatial relationship of the mandible and the fibula graft can be planned individually, which helps achieve optimum appearance and occlusion relationship.

High expression of the autophagy gene Beclin-1 is associated with favorable prognosis for salivary gland adenoid cystic carcinoma.

BACKGROUND: Although autophagy is universally involved in tumorigenesis and tumor progression, the roles of autophagy and autophagy-regulating genes in salivary gland adenoid cystic carcinoma (ACC) remain unknown. In this study, we investigated the expression of the autophagy-regulating genes Beclin-1, death-associated protein kinase-1, ultraviolet radiation resistance-associated gene, and phosphatase and tensin homolog in salivary gland ACC samples. METHODS: Immunohistochemistry and real-time polymerase chain reaction were used to analyze the expression of these genes in 89 ACC samples and normal salivary gland tissue samples. The relationship of their expression with clinicopathological features was analyzed. RESULTS: The data showed significantly lower expression of these genes in the tumor samples than in normal salivary gland tissue samples. Furthermore, Beclin-1 expression was significantly correlated with histological pattern of ACC (P<0.05), and high expression of ultraviolet radiation resistance-associated gene was associated with distant metastasis (P<0.05). Most importantly, univariate and multivariate survival analyses suggested that Beclin-1 protein and mRNA expression in cancer cells were independent prognostic indicators for ACC. CONCLUSION: Our results suggest that autophagy-regulating genes may participate in the pathogenesis of salivary gland ACC. Further research will be required to gain a better understanding of autophagy in ACC.

Mandible reconstruction assisted by preoperative simulation and transferring templates: cadaveric study of accuracy.

PURPOSE: In this study we tried to define tumor resection, fibula cutting, and positioning by surgical templates to perform the mandible reconstruction surgery according to the preoperative simulation. The accuracy was evaluated through cadaveric surgery. MATERIALS AND METHODS: Five cadaveric mandibles and fibulas were obtained. Preoperative surgical simulation was performed. Surgical templates that defined tumor resection, fibula cutting, and positioning were designed and fabricated. Translation, angular deviation, and rotation of bone grafts, as well as translation of condyles, were measured. RESULTS: The reconstructed mandibles showed high similarity to the surgical planning. The mean translation, angular deviation, and rotation of fibula segments of the reconstructed mandibles were 1.35 ± 0.86 mm, 3.36° ± 1.86°, and 8.13° ± 5.35°, respectively. In the mandible remnants, the translation of condyles was measured, with a mean of 1.39 ± 0.66 mm. CONCLUSIONS: Our method of defining the tumor resection, fibula cutting, and positioning by surgical templates was accurate enough for mandible reconstruction surgery.

Foxp3 expressed by tongue squamous cell carcinoma cells correlates with clinicopathologic features and overall survival in tongue squamous cell carcinoma patients.

The forkhead transcription factor, Foxp3, has been identified as a key player in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) function and a definitive marker of Tregs. Recently, it was reported that Foxp3 could be expressed by tumor cells themselves. The present study was to investigate the expression of Foxp3 in tongue squamous cells carcinoma (TSCC) cells and its clinical significance. In this study, the expression of Foxp3 by TSCC cells was demonstrated in TSCC tissue samples and three TSCC cell lines using immunohistochemical staining, realtime-PCR and Western blotting, and its clinical significance were statistically analyzed. The immunohistochemical assay in TSCC paraffin-embedded samples showed positive staining in 48 of 81 (59.3%) cases. The expression was significantly associated with pathologic differentiation (P=0.040) and T stage (P=0.000), and furthermore, inversely associate with patient survival (P=0.021). Multivariate analysis (Cox regression) suggested that Foxp3 expression in TSCC cells was an independent prognostic indicator for TSCC (P=0.032).

Activation of Notch signaling in human tongue carcinoma.

BACKGROUND: Involvement of Notch signaling in several tumors is well known, but its role in tongue squamous cell carcinoma remains poorly characterized. The purpose of this study was to evaluate the roles of Notch signaling in the oncogenesis of tongue carcinoma. MATERIALS AND METHODS: Tumor specimens and adjacent non-neoplastic tongue tissues from 74 patients with tongue carcinoma and human tongue carcinoma cell line Tca8113 were examined using immunohistochemistry and RT-PCR to determine the expressions of Notch1, Notch3, Jagged1, and Jagged2. RESULTS: The mRNA expressions of Notch1, Notch3, Jagged1, and Jagged2 were detected in Tca8113, tongue carcinoma, and adjacent non-neoplastic tongue tissues. The expression levels of mRNAs in tongue carcinoma were higher than those in adjacent non-neoplastic tongue tissues (P < 0.05). Immunohistochemical examination showed that the Notch signal molecules were expressed in Tca8113, tongue carcinoma, and adjacent non-neoplastic tongue tissues. The expression rates of Notch1 and Notch3 protein in tongue carcinoma were higher than those in adjacent non-neoplastic tongue tissues (χ² = 6.10, P = 0.013; χ² = 3.94, P = 0.047). Notch1 and jagged1 were significantly more highly expressed in lymph node metastasis-positive tongue carcinoma (χ² = 6.108, P = 0.013; χ² = 7.354, P = 0.025). In addition, expressions of Notch3 and Jagged2 were highly correlated in tongue carcinoma tissues (χ² = 42.130, P < 0.001). CONCLUSIONS: Expressions of Notch receptors and ligands in tongue carcinoma and adjacent non-neoplastic tongue tissues suggest that Notch signaling may control cell differentiation and proliferation of carcinoma cells. The disorder of Notch signaling may be a mechanism of the tongue carcinoma development.

Sialoendoscopic secondary intervention after failure of open sialolithectomy.

PURPOSE: Traditionally, sialoadenectomy was always indicated when open sialolithectomy failed. The aim of the present study was to investigate the role of sialoendoscopy as the secondary intervention after failure of open sialolithectomy. PATIENTS AND METHODS: A consecutive series of 15 patients with obstructive salivary gland disease with failure of open sialolithectomy were prospectively recruited for our study. All these patients underwent sialoendoscopy under local anesthesia. The reasons for the failure of open sialolithectomy were analyzed, and secondary interventions were performed using sialoendoscopy. RESULTS: Failure of open sialolithectomy resulted from 4 main causes. Small stones could not be found after the duct was incised (n = 3); the stones were pushed posteriorly during open surgery (n = 4); the stones located in the anterior part of the duct were removed, but the hilar stones were left untouched (n = 5); and radiolucent stones were missed (n = 3). All the patients were treated successfully by sialoendoscopy. No symptoms or signs of recurrence developed during a median follow-up period of 16 months. CONCLUSIONS: Sialoendoscopy can be recommended as an effective secondary intervention after failure of open sialolithectomy.

Sialoendoscopically assisted open sialolithectomy for removal of large submandibular hilar calculi.

PURPOSE: The management of large hilar calculi is a technically challenging issue during sialoendoscopic surgery. The aim of the present study was to evaluate the clinical efficacy of sialoendoscopically assisted open sialolithectomy for the removal of large submandibular hilar calculi to avoid sialoadenectomy. PATIENTS AND METHODS: The present study was undertaken among patients with sialolithiasis scheduled for sialoendoscopic surgery from August 2005 to October 2008. When we failed to remove large submandibular hilar stones intraductally, we performed sialoendoscopically assisted open sialolithectomy. The clinical characteristics, pre- and intraoperative data, and outcomes were documented in a prospective fashion. RESULTS: Of 78 consecutive patients with submandibular sialolithiasis, 18 were treated with sialoendoscopically assisted open sialolithectomy immediately after failure of intraductal removal of calculi by sialoendoscopy. For 17 patients, large hilar sialoliths were successfully removed using this surgical technique. The surgery failed in 1 patient with multiple sialoliths, and the procedure was converted to open sialoadenectomy. Temporary numbness of the tongue for 1 week postoperatively was documented in 3 patients. The patients were followed up for a median period of 18 months without any symptoms or signs of recurrence. CONCLUSION: Our results suggest that sialoendoscopically assisted open sialolithectomy is an effective and safe surgical technique to remove large submandibular hilar calculi.

Detection of Notch signaling molecules in cemento-ossifying fibroma of the jaws.

BACKGROUND: The aim of this study was to evaluate the roles of Notch signaling in the oncogenesis and cytodifferentiation of cemento-ossifying fibroma, the expressions of Notch receptors and ligands were detected in COF and normal jaw bones. MATERIALS AND METHODS: The expressions of Notch1, Notch3, Jagged1, and Jagged2 were detected by reverse transcriptase polymerase chain reaction and immunohistochemistry respectively in 16 cases of normal bone tissues and 12 cases of COF of the jaws. RESULTS: The mRNAs expressions of Notch1, Notch3, Jagged1, and Jagged2 were detected in all specimens. The expression levels of mRNAs in COF were higher than those in normal bones. In COF, Notch proteins staining were showed extensively distribution in fibroblasts and osteoblasts. In normal bone tissue, Notch proteins were expressed in osteoblasts, whereas proteins staining were weaker than those in COF, but no detection in fibroblast-like bone marrow stroma cells. The expressions of Notch receptors and ligands were not detected in cementum-like products or bone matrices. CONCLUSION: Our data suggest that Notch signaling may participate in controlling cell differentiation and proliferation in normal bone and COF of the jaws. Notch signaling disorder may be a molecular incident in COF occurrence and development.

[A comparison of three methods in establishing transplanted model of VX2 tongue carcinoma in rabbits].

OBJECTIVE: To establish transplanted models of VX2 tongue carcinoma in rabbits by three methods and compare these models. METHODS: After establishment of VX2 tumor-bearing rabbits, 72 New-Zealand white rabbits were randomly divided into 3 groups. Intact tumour tissue, modified tumour cell suspension, tumour cell suspension were respectively injected into the middle-third lateral border of the tongues of rabbits in 3 groups to induce transplanted VX2 tongue carcinoma. The histological features, the tumour-take rates and the metastasis rates of the 3 models were observed. RESULTS: The tumour-take rate of 3 models were 83.3%, 91.7% and 33.3% respectively; the lymph node metastasis rates were 71.4%, 100.0% and 37.5% respectively; the lung metastasis rates were 35.7%, 81.3% and 0 respectively. The histological features of the transplanted VX2 tongue carcinoma of 3 models were all consistent with those of moderately differentiated carcinoma. CONCLUSION: The biological properties of the transplanted VX2 tongue carcinoma of 3 models is much alike to tongue carcinoma in humans. The model established with modified tumor cell suspension is considered to be more suitable for tongue cancer study.

[Functional hemitongue reconstruction with free forearm flap].

OBJECTIVE: To investigate the clinical application of free forearm flap in the functional hemitongue reconstruction. METHODS: From July 2002 to November 2006, 40 patients with tongue cancer underwent hemiglossectomy and primary hemitongue reconstruction with free forearm flaps. In some cases, the lateral antebrachial cutaneous nerves of the flaps were anastomosed with the lingual nerve to restore the flap sensation. RESULTS: All patients recovered uneventfully after surgery with no morbidity in the donor site. All free flaps survived. The average follow-up period was 2 years and 6 months. The aesthetic and functional results were both satisfactory. The swallowing and speech function were almost normal. The flap sensation was partially restored. CONCLUSIONS: Good functional hemitongue reconstruction can be achieved with free forearm flaps.

[Reconstruction of the tongue with lateral arm free flap after hemiglossectomy].

OBJECTIVE: To investigate the value of microsurgical reconstruction of the tongue after hemiglossectomy with lateral arm free flaps in the treatment of tongue cancer. METHODS: From October 2006 to April 2007, ten patients underwent simultaneous reconstruction of the tongue and oral floor defects with lateral arm free flaps after resection of squamous cell carcinoma of tongue in our hospital. The flaps ranged from 8 cm x 5 cm to 9 cm x 6 cm in size, and were adjusted to the defect of the tongue. The vascular pedicle included the posterior radial collateral artery and the accompanying veins. The outcome of reconstruction was evaluated by follow-up examinations, including the contour and mobility of the reconstructed tongue, the swallowing function and the speech function. RESULTS: All patients recovered uneventfully from surgery, without any major postoperative complications. The transplanted flaps survived. During follow-up period the contour of the reconstructed tongues was satisfactory. The patients demonstrated good functional mobility of the reconstructed and remaining tongue. Postoperatively, the swallowing and speech function was nearly at normal levels and the patients could ingest a solid or semisolid diet. CONCLUSIONS: Microvascular reconstruction of the tongue with lateral arm free flaps after hemiglossectomy is an ideal and safe method, but long term results need to be further studied.

[Effect of percutaneous intervention on adrenomedullin and tumor necrosis factor in the coronary circulation].

OBJECTIVE: To evaluate the effect of percutaneous intervention (PCI) on coronary circulation levels of adrenomedullin (ADM) and tumor necrosis factor alpha (TNF-alpha) in patients with coronary heart disease (CHD). METHODS: Thirty-three CHD patients underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting (altogether 48 stents were implanted). Blood samples were collected from the coronary sinus and femoral artery at the time points of immediately before and after angioplasty, immediately after PTCA or stenting, 10 min after procedures, respectively. RESULTS: The ADM and TNF-alpha levels in the coronary sinus varied little after coronary angiography, but were elevated markedly following PTCA from the basal levels of 36.3+/-1.3 pg/ml to 28.9+/-1.9 pg/ml (P<0.01) and from 11.10+/-0.46 ng/ml to 8.84+/-0.37 ng/ml (P<0.01), respectively. Further increases of ADM and TNF-alpha levels were detected immediately after stent deployment. ADM recovered to basal levels 10 min after completion of the procedures, while TNF-alpha underwent further increase. Before the procedure, ADM and TNF-alpha levels were higher in the coronary sinus than in the femoral artery (28.9+/-1.9 pg/ml vs 22.6+/-0.8 pg/ml, P<0.01; 8.84+/-0.37 ng/ml vs 7. 56+/-0.23 ng/ml, P<0.01, respectively), and their levels in the femoral artery did not undergo significant changes in response to the operations. CONCLUSION: The coronary circulation levels of ADM and TNF-alpha increase after PTCA and stenting but not after coronary angiography in CHD patients, which might be attributed to injuries by the procedures as well as the mechanical stimulation by the stent.