LINC02257 regulates colorectal cancer liver metastases through JNK pathway.

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Repair of a "long and narrow" skin defect of the upper extremity with a modified design of a compound SCIP flap: a series of 12 cases.

BACKGROUND: Large skin lesions of the upper extremity tend to be ''long and narrow'' in shape, and the currently used repair and reconstruction protocols still have some drawbacks, including difficulty in closure of the donor area, poor cosmetic appearance of the donor and recipient areas, and low flap survival rates. The ilioinguinal flap has been more widely used for repair and reconstruction of various complex conditions. In order to improve the versatility of the flap design and to achieve better aesthetic results, we report a study on the improved design of Compound SCIP flap for repairing "long and narrow" large skin defects of the upper extremity by using a modified design of the ilioinguinal flap for the procurement of perforating blood vessels and flap excision. METHODS: From April 2005 to August 2015, a total of 12 patients underwent this modified design procedure, in which the anterior branch of the fourth lumbar artery or the posterior intercostal artery was selected to provide blood supply for the perforator flap together with the superficial branch of the superficial iliac artery to meet the blood supply needs of the flap for the one-time repair of a large "long and narrow" skin defect in the upper limb. Patient demographics, flap characteristics, and associated complications were retrospectively analyzed. RESULTS: 3 females and 9 males were included in this study, the mean age of the patients was 31.7 years (range, 22-44 years), the mean follow-up period was 15.3 ± 5.6 months (range, 7-24 months), and all patients had complete closure of the defect site and donor area, and all flaps survived. CONCLUSIONS: The Compound SCIP flap presents some advantages in repairing 'long and narrow' skin defects in the upper limb. While ensuring the survival rate of the elongated ilioinguinal flap, it amplifies the benefits of the ilioinguinal flap and enhances skin utilization. This can serve as a beneficial choice for repairing 'long and narrow' skin defects in the upper limb.

Spatio-temporal evolution law of gas-temperature coupling field in "110 method" goaf and prevention of spontaneous combustion.

To investigate the distribution characteristics of spontaneous combustion disaster (SCD) zones in the goaf of "110" mining method with U + L ventilation system and formulate corresponding fire prevention measures, enclosed coal oxidation experiments were carried out to measure the oxidation characteristics of Dongrong Coal Mine bituminous coal sample. A coupled 3DEC-CFD (3 dimensional Distinct Element Code) model was established. The 3D transient distribution characteristics of SCD zones in the "110" mining goaf under U+L ventilation condition were analyzed. Nitrogen injection in the tailgate was proposed for coal spontaneous combustion prevention. The results show that air leakage changed the distribution of oxygen and temperature fields in the "110" goaf, causing the region 20~60 m parallel to the retained roadway to remain in the oxidation zone for spontaneous combustion. As the working face advanced, the area change curve of SCD zones in the "110" goaf exhibited a "double inflection point" pattern. Eliminating the "retained roadway oxidation zone" can effectively reduce the spontaneous combustion risks in the "110" goaf and ensure mining safety. This study enriches the mechanisms of coal spontaneous combustion.

New tranylcypromine derivatives containing sulfonamide motif as potent LSD1 inhibitors to target acute myeloid leukemia: Design, synthesis and biological evaluation.

Lysine-specific demethylase 1 (LSD1) is frequently elevated in acute myeloid leukemia (AML) and often leads to tumorigenesis. In recent years, numerous LSD1 inhibitors based on tranylcypromine (TCP) scaffolding have reached clinical trials. Most TCP derivatives were modified at the amino site of cyclopropane motif. Herein, we for the first time introduced a sulfonamide group in TCP benzene ring of series a compounds and performed a systematical study on structure and activity relationships by varying sulfonamide groups. The introduction of sulfonamide significantly increased the targeting capacity of TCP against LSD1. Moreover, we discovered that the Boc attached LSD1 inhibitors (labelled as series b compounds) substantially improved their anti-proliferation capacity towards AML cells. The intracellular thermal shift and LC-MS/MS results implied that Boc enhanced the drug lipophilicity and might be removed under the cancerous acidic environment to release the real pharmacophore, evidenced by the fact that a structurally similar but acidic inert pivaloyl to replace Boc dramatically dropped the cellular anti-proliferation effect. Finally, a benzyl group installed at the amino site to appropriately increase lipophilicity led to trans-4-(2-(benzylamino)-cyclopropyl)-N,N-diethylbenzenesulfonamide a10 that showed better anti-proliferation activity in AML cells and enzymatic inhibition against LSD1. Taken together, our work offers a novel TCP-based structure and provides a prodrug strategy for the discovery of potent LSD1 inhibitors by having appropriate lipophilicity.

miR-940 inhibits cell proliferation and promotes apoptosis in esophageal squamous cell carcinoma cells and is associated with post-operative prognosis.

The present study aimed to examine microRNA (miR)-940 expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, analyze its association with the clinicopathological features and prognosis of patients, and explore the potential underlying mechanisms. miR-940 expression in ESCC cell lines and a normal esophageal cell line was detected using reverse transcription-quantitative (RT-q)PCR. Furthermore, 210 resected ESCC tissue and para-carcinoma tissue specimens were collected, and miR-940 expression in those tissues was detected by RT-qPCR. In addition, the association of miR-940 with the clinicopathological features and prognosis of patients was analyzed. In an in vitro experiment, miR-940 mimics were transduced into ESCC cells by the liposome method. An MTT assay was used to detect the effect of miR-940 on the viability of ESCC cells. The influence of miR-940 on the cell cycle and apoptotic rate of ESCC cells was detected by flow cytometry. The present results indicated that the expression levels of miR-940 in human ESCC tissues and cell lines were markedly downregulated, and that low expression of miR-940 in ESCC tissues was significantly associated with a poor degree of differentiation, positive lymph node metastasis and advanced clinical stage. Kaplan-Meier survival analysis suggested that low miR-940 expression was associated with poor prognosis. Cox regression analysis revealed that lymph node metastasis, clinical stage and miR-940 expression were independent risk factors affecting the prognosis of patients. Overexpression of miR-940 in ESCC cells markedly reduced the cell viability, blocked the cell cycle at G0/G1 phase and promoted cell apoptosis. These results suggest that miR-940 is downregulated in ESCC, which is linked to the occurrence and progression of ESCC. Conversely, overexpression of miR-940 reduced the cell viability and promoted apoptosis of ESCC cells. Therefore, miR-940 may be a promising novel prognostic marker and anti-cancer target in ESCC.

Prognostic significance of TPX2 and NIBP in esophageal cancer.

The expression of targeting protein for Xenopus kinesin-like protein 2 (TPX2) and NIK-IKK-ß binding protein (NIBP) in patients with esophageal cancer were investigated. A total of 250 samples of cancer tissue and 250 samples of adjacent normal tissue were collected from 250 patients who underwent radical resection of esophageal cancer in Weihai Central Hospital from March 2011 to February 2014. RT-qPCR was used to detect the relative expression of TPX2 and NIBP. The relative expression of TPX2 and NIBP in esophageal cancer tissues was statistically higher than those in adjacent normal tissues (P<0.05). TPX2 and NIBP levels in tumor tissues with lymph node metastasis were significantly higher than those in tissues without lymph node metastasis (P<0.05). There was a significant difference in the relative expression of TPX2 and NIBP in different degrees of infiltration (P<0.05). Tissues with a TPX2 level equal to or higher than the average TPX2 level (1.465) were divided into TPX2 high expression group, while tissues with a TPX2 level below the average were divided into TPX2 low expression group. The 5-year overall survival rate of TPX2 high expression group was significantly lower than that of TPX2 low expression group (P<0.05). Tissues with a NIBP level equal to or higher than the average NIBP level (0.498) were included in the NIBP high expression group, while tissues with a NIBP level below the average were included in the NIBP low expression group. The 5-year overall survival rate of NIBP high expression group was significantly lower than that of NIBP low expression group (P<0.05). TPX2, NIBP, TNM staging, lymph node metastasis, and degree of infiltration were independent prognostic factors affecting overall survival (P<0.05). In conclusion, owing to their high expression in esophageal cancer tissues, TPX2 and NIBP are potentially important biomarkers for the evaluation of TNM stage, metastasis, and prognosis of esophageal cancer.

MiR­495 suppresses cell proliferation by directly targeting HMGA2 in lung cancer.

The present study aimed to investigate the expression of microRNA­495 (miR­495) in non­small cell lung cancer (NSCLC) tissues and cells, as well as its function on the proliferation of lung cancer cells. The expression of miR­495 in 122 pairs of NSCLC tissues and matched paracarcinoma tissues, as well as in human lung cancer cell lines (A549, H460, H1650, H520 and SK­MES­1) and the normal human pulmonary bronchial epithelial cell line 16HBE was determined using reverse transcription quantitative polymerase chain reaction (RT­qPCR). As predicted by bioinformatics analysis, high mobility group A2 (HMGA2) may be a potential target gene of miR­495. In addition, the regulatory function of miR­495 on its target gene HMGA2 was evaluated using a dual­luciferase reporter assay, RT­qPCR and western blotting. Furthermore, the effect of miR­495 on the proliferation of A549 lung cancer cells was investigated using a Cell Counting Kit­8 (CCK­8) assay. The results demonstrated that the expression of miR­495 in NSCLC tissues and cells was significantly downregulated compared with the control. In addition, downregulated expression of miR­495 was associated with tumor differentiation, lymph node metastasis and tumor, node and metastasis staging. Additionally, a dual­luciferase reporter assay revealed that miR­495 could directly associated with the 3'­untranslated region of HMGA2. Upregulated expression of miR­495 significantly downregulated the mRNA and protein expression levels of HMGA2 in A549 cells. Furthermore, the results of CCK­8 assay revealed that upregulated expression of miR­495 significantly suppressed the proliferation of A549 cells; HMGA2 overexpression reversed this inhibition. In summary, the findings of the present study demonstrated that miR­495 was downregulated in NSCLC tissues and cells. In addition, miR­495 suppressed the proliferation of lung cancer cells by directly targeting HMGA2.

Relayed Regioselective Alkynylation/Olefination of Unsymmetrical Cyclic Diaryliodonium Species Catalyzed by Cu and Pd: Affording Fluorescent Cytotoxic Benzoxazoles.

Although cyclic diaryliodonium species have the potential to act as valuable synthons for cascade transformations, they still remain largely unexplored. The regioselectivity associated with unsymmetrical cyclic diaryliodonium species has previously been known to pose a challenge. A regioselective relayed alkynylation and olefination of unsymmetrical cyclic diaryliodonium species has been achieved by installation of a directing amido group. These relayed transformations were delayed until an oxazole ring had formed, delivering a series of unique fluorescent benzoxazoles. Moreover, some of these synthetic benzoxazoles showed apparent inhibitory activity against malignant cancer cells. Further confocal visualization revealed that benzoxazoles targeted cell nuclei. These findings might provide a novel structural scaffold to develop desirable anticancer agents.

[Optimizing the method for 31P-NMR analysis of organic phosphorus from wetland sediments].

Solution 31P-Nuclear Magnetic Resonance (NMR) is an analysis technology which has been an effective means for the analysis of environmental organic phosphorus. However, the method is rarely applied in the study of wetlands so that the corresponding researches about wetland sediment sample preparation method also very deficient. The present study was aimed to find the most suitable sample preparation method for 31P-NMR analysis of the artificial wetland sediments, using different extractant (NaOH or 0.25 mol x L(-1) NaOH + 0.05 mol x L(-1) EDTA as main extractant, and 1M HCl as pre-extractant or not), sample to extractant ratio (1 : 8 or 1 : 10), centrifugation conditions and scans time and so on. The results showed that the best 31P-NMR spectrum could be obtained with freeze-ried, ground and sieved sediments, 1M HCl as pre-extractant for 16 h, NaOH + 0.05 mol x L(-1) EDTA as main extractant for 16 h, extraction ratio of 1 : 8, and low temperature and high-speed centrifugation (4 degrees C, 10 000 r x min(-1) for 30 min) for avoiding hydrolysis of certain components. Besides, choosing much longer NMR scan time, as 14-16 h (scans about 25 000 times), could get more complete spectral signals spectrum. And finally, four kinds of P-compounds (orthophosphate, orthophosphate monoesters, orthophosphate diesters and pyrophosphate) were detected in the NMR spectrum. But neither polyphosphate nor phosphonates was not found in all these experiments, which need further study. Compared with the traditional chemical analysis method, 31P-NMR method of sample preparation is relatively simple. Then it is less destructive with components distinguished completely. Using 31P-NMR technology, the cognition of wetland phosphorus cycle, especially organophosphate, will be expected to get new breakthrough.

[Classification and treatment of whole hand degloving injury].

OBJECTIVE: To summarize the injury characteristics of the whole hand degloving injury and to explore its classification and treatment. METHODS: Between December 1999 and May 2010, 41 cases of the whole hand degloving injury were admitted for treatment. There were 28 males and 13 females with an average age of 35 years (range, 18-58 years). The causes of injury included mangled injury in 28 cases and crush injury in 13 cases. The interval between injury and surgery was 1-10 hours (mean, 3 hours). According to self-made classification standard for whole hand degloving injury, 11 cases were rated as type I, 5 cases as type II, 4 cases as type III, 8 cases as type IV, and 13 cases as type V. Type I injury was treated by replantation surgery with vascular anastomosis, type II by reconstruction with thumb flap and the second toe containing dorsal skin flap, type III by reconstruction with the second toe containing dorsal skin flap of both feet, type IV by replantation surgery with vascular anastomosis, and type V by reconstruction with thumb flap containing dorsal skin flap (8 cases) or repairing with abdominal flap (5 cases). The size of the dorsal flap was between 9 cm x 6 cm and 17 cm x 11 cm and the dorsal donor site was covered with free skin grafting. RESULTS: After surgery, partial necrosis occurred at fingers in 6 patients with type I injury, and at fingers and palm skin in 6 patients with type IV injury; the flaps, the reconstructed fingers, and replanted skin all survived in the others. The grafted skin at donor sites successfully healed. Forty cases were followed up from 6 months to 7 years (mean, 14 months). The skin color and texture were close to normal hand in the cases undergoing replantation, who had the best function restoration with S2-S4 sensory recovery; the hand function was basically restored with S2-S3 sensory recovery in the cases undergoing finger reconstruction with thumb and toe flaps; and the restoration of the hand function was not satisfactory with S1-S2 sensory recovery in the cases undergoing abdominal flaps. CONCLUSION: Whole hand degloving injury can be classified into different types according to injury degree and this will help choose the clinical treatment plan. The appropriate treatment based on these

An anatomic and clinical study of the adductor magnus tendon-descending genicular artery bone flap.

The composite tissue flap of the descending genicular vessels with the adductor magnus tendon is a newly developed, reliable method to repair the Achilles tendon and relevant skin defects. The aim of this study was to evaluate the anatomy of the adductor magnus tendon-descending genicular artery bone flap, and the feasibility and value for the repair of the Achilles tendon and relevant skin defects. There were 34 adult specimens used for the anatomy of this flap. The descending genicular artery originates 10.5 ± 1.6 cm above the adductor tubercle, with a diameter of 1.8 ± 0.6 mm and a length of 1.2 ± 0.5 cm. Its articular branch is distributed in the adductor magnus tendon and the medial condyle of the femur. The saphenous branch has a diameter of 1.1 ± 0.3 mm and is distributed in the skin of the upper medial calf. A total of 16 cases of trauma-induced Achilles tendon damage and calcaneus and skin defects were repaired with the vascularized adductor magnus tendon bone flap, including the reconstruction of Achilles tendon insertion and repair of relevant skin defects. All of the composite tissue flaps were viable, the skin sensation of the flaps was recovered, and all patients walked with a normal gait. Our results suggested that the adductor magnus tendon-descending genicular artery bone flap is an alternative method to repair composite tissue defects of the Achilles tendon.

[Repair of whole-hand destructive injury and hand degloving injury with transplant of pedis compound free flap].

OBJECTIVE: To investigate the surgical method and clinical efficacy of repairing whole-hand destructive injury or hand degloving injury with the transplant of pedis compound free flap. METHODS: From February 2003 to June 2008, 21 patients with whole-hand destructive injury or hand degloving injury were treated, including 15 males and 6 females aged 18-45 years old (average 25 years old). The injury was caused by punching machine crush in 10 cases, roller crush in 7 cases, and imprinter crush in 4 cases. The time between injury and operation was 1-9 hours. Eleven cases had the skin-degloving injury of the whole hand, while the other 10 cases had the proximal palm injury combined with dorsal or palmar skin and soft tissue defect. After debridement, the size of wound was 9 cm x 7 cm-15 cm x 10 cm in the dorsal aspect and 10 cm x 7 cm-6 cm x 10 cm in the palmar aspect. The defect was repaired by the thumbnail flap of dorsalis pedis flap and the second toenail flap of dorsalis pedis flap in 5 cases, the thumbnail flap of dorsalis pedis flap and the second toe with dorsalis pedis flap in 4 cases, and bilateral second toe with dorsalis pedis flap in 12 cases. The flap area harvested during operation ranged from 6 cm x 5 cm to 16 cm x 11 cm. Three fingers were constructed in 2 cases and two fingers in 19 cases. Distal interphalangeal joint toe amputation was conducted in the thumbnail flap donor site, metatarsophalangeal joint toe amputation was performed in the second toenail flap donor site, and full-thickness skin grafting was conducted in the abdomen. RESULTS: At 7 days after operation, the index finger in 1 case repaired by the second toenail flap suffered from necrosis and received amputation, 1 case suffered from partial necrosis of distal dorsalis pedis flap and recovered after dressing change, and the rest 42 tissue flaps survived. Forty-three out of 44 reconstructed fingers survived. All the wounds healed by first intention. At 2 weeks after operation, 2 cases had partial necrosis of the donor site flap and underwent secondary skin grafting after dressing change, the rest skin grafts survived, and all the wounds healed by first intention. Nineteen cases were followed up for 6-36 months (average 11 months). The flaps of palm and dorsum of hand showed no swelling, the reconstructed fingers had a satisfactory appearance and performed such functions as grabbing, grasping, and nipping. The sensory of the flaps and the reconstructed fingers recovered to S2-S4 grade. The donor site on the dorsum of the foot had no obvious scar contracture, without obvious influence on walking. CONCLUSION: For the whole-hand destructive injury or hand degloving injury, the method of transplanting pedis compound free flap can repair the defect in the hand and reconstruct the function of the injured hand partially. It is an effective treatment method.

Reconstruction of soft tissue defect of the extremity with the perforator flap from inguinal region.

BACKGROUND: The perforator flap has become a very useful reconstructive means of soft tissue defect of extremities. The perforator flap from the inguinal region has advantages that include the ability to cover a large area with little donor site morbidity and provision of suitable thickness for reconstruction. METHODS: From July 1, 2005 to June 30, 2007, 10 patients with various types of soft tissue defect underwent reconstruction with 10 perforator flaps from the inguinal region. Six flaps were applied to the upper extremities and four flaps to the lower extremities. The dimensions of the transferred flaps ranged from 7-30 cm in length and 4-10 cm in width. RESULTS: The postoperative course of all 10 flaps was uneventful and all flaps survived. Distal small partial necrosis was observed in one case due to arterial insufficiency of the distal part of the flap. All patients were satisfied with the functional and esthetic resurfacing outcome. CONCLUSION: Use of perforator flap from the inguinal region could overcome the disadvantages of the traditional free groin flap, and represents a safe and useful tool for coverage of soft tissue defects.