Endoscopic dacryocystorhinostomy with mucosal anastomosing in chronic dacryocystitis with three categories of ethmoid sinuses.

AIM: To evaluate the outcome of endoscopic dacryocystorhinostomy (En-DCR) with mucosal anastomosis in chronic dacryocystitis patients, with various categories of ethmoid sinuses. METHODS: Between July 2015 and September 2019, 1439 adult patients, representing 1623 affected eyes, presented with chronic dacryocystitis and were scheduled for En-DCR. The categories of ethmoid sinuses were preoperatively determined, using computed tomography-dacryocystography (CT-DCG), and were classified as category 1 (C1), category 2 (C2), and category 3 (C3). No sinuses anterior to the posterior lacrimal crest defined as C1. Sinuses found between the anterior edge of the lacrimal bone and the posterior lacrimal crest defined as C2. Sinuses found anterior to the lacrimal bone suture defined as C3. At the end of surgery, the dacryocyst and nasal mucosa were anastomosed in C1, and the dacryocyst mucosa and anterior ethmoid sinus were anastomosed in C2 and C3 ethmoid sinus patients. The surgical success rate and related complications, in patients with 3 categories of ethmoid cells, were monitored and documented. RESULTS: Postoperative data was obtained for 179 C1 affected eyes, 878 C2 affected eyes, and 432 C3 affected eyes. The overall success rate of En-DCR was 93.0% (1385/1489). Additionally, the success rates were comparable among the different ethmoid categories at 12mo post operation. We demonstrated that the major reason for surgical failure was intranasal ostial closure, due to granulation or scar tissue. CONCLUSION: En-DCR is a feasible and highly effective primary treatment for chronic dacryocystitis. To ensure surgical success, the surgery protocol must be designed in accordance with the category of ethmoid sinuses present in individual patient.

Management of chronic dacryocystitis cases after failed external dacryocystorhinostomy using endoscopic technique with a novel lacrimal ostium stent.

AIM: To demonstrate the outcomes of endoscopic endonasal dacryocystorhinostomy (En-DCR) with an novel lacrimal ostium stent (LOS) which was performed in patients with recurrent epiphora after failed external dacryocystorhinostomy (Ex-DCR) and analyze the causes of failed Ex-DCR. METHODS: From September 2015 and December 2017, the clinic data of 29 cases suffered from recurrent epiphora after failed Ex-DCR was reviewed. The LOS were implanted into the ostium at the end of the revisional surgery. The causes of failed Ex-DCR were analyzed before revisional surgeries. Outcome of revisional surgeries with the new device were evaluated as well. RESULTS: The major causes of failure of the external approach were synechiae formation in the nasal ostium (29/29), followed by inadequate removal of the bony wall (21/29), nasal synechiae formation between lateral wall of nose and middle turbinate (11/29), and the bone opening was not in good location (7/29). The rate of success after revisional surgery was 82.76%. Re-obstruction of the ostiums were found in 5 failed cases. CONCLUSION: Endoscopic approach with a novel LOS may be an effective procedure to manage recurrent epiphora after previous failed Ex-DCR surgery. Synechiae formation in the nasal ostium and inadequate removal of the bony wall were the major causes of failure of Ex-DCR.

Surgical outcomes in acute dacryocystitis patients undergoing endonasal endoscopic dacryocystorhinostomy with or without silicone tube intubation.

AIM: To establish the necessity of silicone tube intubation in acute dacryocystitis (AD) patients undergoing endonasal endoscopic dacryocystorhinostomy (En-DCR). METHODS: Patients presenting with unilateral AD were randomly assigned to two treatment groups. En-DCR procedures were performed following lacrimal abscess formation, with the operation being performed with silicone intubation for patients in group B but not group A. Functional success was defined by an absence of additional AD episodes, no epiphora, and ostium patency as established via endoscopic evaluation or fluorescein irrigation. Operative success rates and demographic variables were compared between treatment groups. RESULTS: In total, 66 patients were analyzed in the present study (33 per group), with complete postoperative data having been successfully collected from 27 and 22 patients in group A and group B, respectively. All patients exhibited complete resolution of acute inflammation. Upon follow-up, granulation tissue was detected around the ostium at higher rates in group B (9/22, 40.9%) relative to group A (4/27, 14.8%). At the 12-month follow-up time point, patients in group A exhibited higher success rates (25/27, 92.6%) relative to patients in group B (20/22, 90.9%), but this difference was not significant. Cases of lacrimal passage reconstruction failure in both groups were attributed to excessive fibrous and/or granulation tissue formation proximal to the intranasal ostium. CONCLUSION: Given that these two operative approaches are associated with similar rates of operative success and in light of differences in granulation tissue formation, cost, and operative duration, these data do not support the routine silicone intubation of AD patients following En-DCR surgery.

1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway.

The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1α,25(OH)2D3 is a potential anti-oncogenic molecule in various cancers. In the present study, we investigated the radiosensitive effects and underlying mechanisms of 1α,25(OH)2D3 in vitro and in vivo. We found that 1α,25(OH)2D3 enhanced the radiosensitivity of lung cancer and ovarian cancer cells by promoting the NADPH oxidase-ROS-apoptosis axis. Compared to the group that only received radiation, the survival fraction and self-renewal capacity of cancer cells treated with a combination of 1α,25(OH)2D3 and radiation were decreased. Both apoptosis and ROS were significantly increased in the combination group compared with the radiation only group. Moreover, N-acetyl-L-cysteine, a scavenger of intracellular ROS, reversed the apoptosis and ROS induced by 1α,25(OH)2D3, indicating that 1α,25(OH)2D3 enhanced the radiosensitivity of cancer cells in vitro by promoting ROS-induced apoptosis. Moreover, our results demonstrated that 1α,25(OH)2D3 promoted the ROS level via activating NADPH oxidase complexes, NOX4, p22phox, and p47phox. In addition, knockdown of the vitamin D receptor (VDR) abolished the radiosensitization of 1α,25(OH)2D3, which confirmed that 1α,25(OH)2D3 radiosensitized tumor cells that depend on VDR. Similarly, our study also evidenced that vitamin D3 enhanced the radiosensitivity of cancer cells in vivo and extended the overall survival of mice with tumors. In summary, these results demonstrate that 1α,25(OH)2D3 enhances the radiosensitivity depending on VDR and activates the NADPH oxidase-ROS-apoptosis axis. Our findings suggest that 1α,25(OH)2D3 in combination with radiation enhances lung and ovarian cell radiosensitivity, potentially providing a novel combination therapeutic strategy.

Aberrant high expression level of MORC2 is a common character in multiple cancers.

Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types using immunohistochemical staining and analysis of messenger RNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, esophagus, and bladder). We also found that the MORC2 expression level in high-grade cancer tissues was much more elevated and associated with unfavorable pathological characteristics, poor overall survival, and disease-free survival in several kinds of cancers such as non-small cell lung cancer and breast cancer. Gene set enrichment analysis was used to predict the genes modulated by MORC2, and the results showed that dysregulation of MORC2 in tumor may take part in the cell cycle regulation and genomic instability. We observed that MORC2 knockdown would arrest the cell cycle progress, and the genome of tumors with high MORC2 expression contained more point mutations and gene copy number variation, which validates our gene set enrichment analysis results. The results also showed that MORC2 knockdown would significantly inhibit the proliferation, colony forming, migration, and invasion in multiple cancer cell lines. Taken together, these results highlight the importance of MORC2 in tumorigenesis and cancer progression, and it may act as a potential diagnostic marker and therapeutic target for these diseases.

Plant toxin ß-ODAP activates integrin ß1 and focal adhesion: A critical pathway to cause neurolathyrism.

Neurolathyrism is a unique neurodegeneration disease caused by ß-N-oxalyl-L-α, ß- diaminopropionic (ß-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, ß-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca2+ from mitochondria to cellular matrix. Increased Ca2+ in cellular matrix activated the pathway of ECM, and brought about the overexpression of ß1 integrin on cytomembrane surface and the phosphorylation of focal adhesion kinase (FAK). The formation of high concentration of FA units on the cell microfilaments further induced overexpression of paxillin, and then inhibited cytoskeleton polymerization. This phenomenon turned to cause serious cell microfilaments distortion and ultimately cytoskeleton collapse. We also conducted qRT-PCR verification on RNA-sequence data using 8 randomly chosen genes of pathway enrichment, and confirmed that the data was statistically reliable. For the first time, we proposed a relatively complete signal pathway to neurolathyrism. This work would help open a new window to cure neurolathyrism, and fully utilize grass pea germplasm resource under climate change.

1α,25(OH)2D3 Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial-Mesenchymal Transition.

Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)2D3] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)2D3 could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-ß1(TGF-ß1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)2D3 not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-ß1. We discovered that 1α,25(OH)2D3 increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)2D3 reduced the expression level of transcription factors of EMT, such as slug, snail, and ß-catenin. These results indicate that 1α,25(OH)2D3 suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)2D3 might be a potential therapeutic agent for the treatment of ovarian cancer.

[FTIR, FT-Raman and surface enhanced Raman study of S-thyminyl-L-cysteine].

The present paper reports the FT-infrared spectra and FT-Raman spectra of the S-thyminyl-L-cysteine. The optimal concentration of the S-thyminyl-L-cysteine on silver sol is 10(-4) mol L(-1). The interaction of S-thyminyl-L-cysteine with Ag nanoparticles was adsorbed by COO-, NH3+, S, and ring in the tilted way. Amino peak was enhanced in the acidic condition, carboxyl peak was enhanced in alkaline condition. Adsorption of S-thyminyl-L-cysteine on silver nanoparticles was mainly with carboxyl under the acidic condition and with amino under the alkaline condition. Other groups had no change at different pH. Establishment of this adsorption model provided important information and useful reference for further Raman spectra study of PNA, peptides and other biological molecules.

[FT-Raman spectroscopic investigation on hypothyroid cancer].

The normal and malignant tissues from hypothyroid were investigated by FT-Raman spectroscopy. The results show that two characteristic Raman spectral peaks of normal tissues appeared at 503 and 758 cm(-1) (corresponding to theextension vibration of C--I band and the vibration of benzene rings respectively) in the range of 400-3500 cm(-1). The two peaks disappeared at malignant tissues. The intensity of the characteristic vibration peaks of normal tissues appearing at 3 062 and 1 003 cm(-1) corresponding to tyrosine weakened in malignant tissues. Thus, FT-Raman spectroscopy is a potential method in the diagnosis of hypothyroid cancer.

Comparative study on radiosensitivity of various tumor cells and human normal liver cells.

AIM: To investigate the radiation response of various human tumor cells and normal liver cells. METHODS: Cell lines of human hepatoma cells (SMMC-7721), liver cells (L02), melanoma cells (A375) and cervical tumor (HeLa) were irradiated with (60)Co gamma-rays. Cell survive was documented by a colony assay. Chromatid breaks were measured by counting the number of chromatid breaks and isochromatid breaks immediately after prematurely chromosome condensed by Calyculin-A. RESULTS: Linear quadratic survival curve was observed in all of four cell lines, and dose-dependent increase in radiation-induced chromatid and isochromatid breaks were observed in GB2B phase. Among these four cell lines, A375 was most sensitive to radiation, while, L02 had the lowest radiosensitivity. For normal liver cells, chromatid breaks were easy to be repaired, isochromatid breaks were difficult to be repaired. CONCLUSION: The results suggest that the gamma-rays induced chromatid breaks can be possibly used as a good predictor of radiosensitivity, also, unrejoined isochromatid breaks probably tightly related with cell cancerization.

Effect of exogenous wild-type p53 on melanoma cell death pathways induced by irradiation at different linear energy transfer.

We investigated the effect of exogenous wild-type p53 on the radiation-induced cells apoptosis and necrosis at different levels of linear energy transfer (LET) to evaluate its mechanisms. The human melanoma cell line A375, which bears wild-type p53 gene status, was used, as well as the transfectant A375 cells (A375/p53) with adenoviral vector containing the wild-type p53 gene. We exposed these cells to X-rays and to accelerated carbon-ion (C-) beams. Cellular sensitivities were determined by using clonogenic assay. Apoptotic and necrotic cell deaths were determined morphologically by dual staining (acridine orange and ethidium bromide) using fluorescence microscopy. We discovered that (1) there was no significant difference in survival fraction between A375 cells and A375/p53 cells irradiated by C-beams with greater than 32 KeV/microm LET, (2) although apoptosis in the two kinds of cells increased in an LET-dependent manner, exogenous wild-type P53 induced cell apoptosis efficiently in A375/p53 relative to A375 cells with X-rays or high-LET irradiation, and (3) by high-LET irradiation, the number of necrosis in A375 cells increased significantly (P < 0.05) in comparison with A375/p53 cells. These results indicate that in high-LET irradiation apoptosis induction is p53 dependent partly and exogenous wild-type P53 plays an important role in modulating cell death type, although there was no significant difference in cellular radiosensitivities. Our observation in the study offers the potential application of high-LET radiation combined with p53 in the management of human patients with melanoma.