UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

BackgroundPancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established.MethodsUBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose.ResultsUBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP.ConclusionsIn conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.     

Intraoperative malignant glaucoma during femtosecond laser-assisted cataract surgery: A case report

Rationale:Femtosecond laser-assisted cataract surgery (FLACS) has grown in popularity among ophthalmologists as a novel surgical technique. However, malignant glaucoma (MG) is a complication of FLACS. Herein, we report a case of MG following FLACS.Patient concerns:A 66-year-old woman presented with complaints of blurred vision in the right eye and a foreign body sensation in both eyes. Ophthalmological examinations showed that the corrected distance visual acuity was 20/50 and 20/25 in the right and left eyes, respectively. Without any topical anti-glaucoma medication, the intraocular pressure (IOP) was 20 mmHg in the right eye and 17 mmHg in the left eye. Slit-lamp examination of the right eye revealed a transparent cornea with a defect in the punctate overlying epithelium; the central anterior chamber depth was shallow the peripheral iris laser shot was visible, the pupil was normal, and the lens was mainly cortical opacified.Diagnoses:Based on the patient''s symptoms, examination results, and preliminary diagnoses, age-related cataract in the right eye, binocular post-antiglaucoma surgery, pseudophakicin in the left eye, and Sjogren syndrome were included.Interventions:FLACS was performed to facilitate anterior capsulotomy and segmentation of the nucleus in the right eye. MG occurred after the femtosecond procedure, and with the treatment of medicines combined with phacoemulsification, IOP was eventually normal without further antiglaucoma therapy.Outcomes:IOP was 16 mmHg on postoperative day 1. Ocular ultrasonography revealed no choroid detachment or hemorrhage in the right eye. Two weeks postoperatively, uncorrected visual acuity was 20/25, and IOP remained normal with no further antiglaucoma treatment on 1 month postoperatively.Conclusions:We describe the occurrence of MG after FLACS and illustrate that miosis and bubble formation after FLACS may be risk factors for MG during FLACS.     

Serum transfer RNA‐derived fragment tRF‐31‐79MP9P9NH57SD acts as a novel diagnostic biomarker for non‐small cell lung cancer

BackgroundtRNA‐derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the function of tRFs in non‐small cell lung cancer (NSCLC) is yet unknown. The goal of this study was to assess the tRF‐31‐79MP9P9NH57SD serum expression from NSCLC patients and to determine its diagnostic usefulness.MethodsBy using stem‐loop quantitative real‐time PCR, we were able to detect various tRF‐31‐79MP9P9NH57SD expressions in 96 NSCLC serum samples, 96 healthy controls, and 20 pairs of NSCLC serum samples pre‐ and post‐surgery (qRT‐PCR). After that, we analyzed its diagnostic effectiveness using the receiver operating characteristic (ROC) curve.ResultsSerum tRF‐31‐79MP9P9NH57SD expression was higher in NSCLC patients, and levels of tRF‐31‐79MP9P9NH57SD were linked to the clinical stage (p = 0.002) and the malignancy of lymph node (p = 0.012). In addition, after the procedure, the serum tRF‐31‐79MP9P9NH57SD expression in NSCLC patients dropped. With 48.96 percent sensitivity and 90.62 percent specificity, the area under ROC curve (AUC) was 0.733.Conclusionserum tRF‐31‐79MP9P9NH57SD possibly is a new and groundbreaking biomarker for the NSCLC.     

Clinical application of metagenomic next‐generation sequencing technology in the diagnosis and treatment of pulmonary infection pathogens: A prospective single‐center study of 138 patients

IntroductionRapid and accurate pathogen identification is essential for the treatment of pneumonia. Metagenomic next‐generation sequencing (mNGS) is a newly developed technology to obtain microbial nucleic acid sequence information quickly, efficiently, and without bias.MethodsWe performed shotgun metagenomic next‐generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for pathogen identification in pneumonia in a prospective study with 138 patients from a single center. We compared the results of mNGS with standard methods including culture, staining, and targeted PCR and evaluated the clinical applicability of mNGS.ResultsMost of the patients (128/138, 92.75%) were cured or improved. One patient (1/138, 0.72%) died because of acute gastrointestinal bleeding, and 9 patients (9/138, 6.52%) showed no improvement. mNGS identified more bacteria (53 versus 27), fewer fungi (8 versus 31), and more viruses (16 versus 1) than standard methods. In total, treatment in 34 out of 138 cases (24.64%) was adjusted and optimized because of mNGS results. Positive mNGS results contributed to a definitive diagnosis in 23 cases (16.67%), which helped guide treatment decision by either adjusting the antibiotics without de‐escalation or continuing the empirical treatment. mNGS also confirmed no active infection in 11 cases (7.97%) allowed for antibiotic de‐escalation.ConclusionThis prospective clinical study evaluated the clinical utility of mNGS for the diagnosis of pneumonia and showed that mNGS of BALF provides valuable information for effective treatment.     

Hand-assisted laparoscopic versus laparoscopic-assisted radical gastrectomy in the treatment of advanced distal gastric cancer: final results of a single-center randomized study

ObjectiveTo compare the results and 5- and 8-year overall survival (OS) and disease-free survival (DFS) of hand-assisted laparoscopic surgery (HALS) and laparoscopic-assisted surgery (LAS) in radical gastrectomy for advanced distal gastric cancer.MethodsA total of 124 patients admitted to our institution from May 2009 to April 2013 were randomly divided into a HALS group (n = 62) and a LAS group (n = 62). Postoperatively, 110 patients were followed for 5 and 8 years, and 14 patients were lost to follow-up. The 5- and 8-year OS and DFS rates of the groups were compared and analyzed.ResultsThe 5- and 8-year OS rates, respectively, were 38.8% and 19.4% in the HALS group and 38.3% and 15.3% in the LAS group (log-rank test, χ² = 0.250). The 5- and 8-year DFS rates, respectively, were 23.1% and 10.6% in the HALS group and 19.3% and 11.6% in the LAS group (log-rank test, χ² = 0.109). No significant differences were found.ConclusionCompared with LAS, HALS radical gastrectomy for advanced distal gastric cancer had a lower conversion rate to open surgery, shorter surgical duration, and more thorough dissection of lymph nodes; 5- and 8-year OS and DFS rates were similar to those with LAS.     

大鼠肠道菌群对长梗冬青苷体外代谢的影响

摘 要 目的：探究体外孵育的大鼠肠道菌群对长梗冬青苷的代谢转化规律。方法: 将长梗冬青苷与大鼠肠道菌群在厌氧条件下共孵育,分别于0,4,8,12,24,48 h时取样,经乙酸乙酯萃取后采用HPLC法进行定性和定量分析。结果: 在与大鼠肠道菌群共孵育48 h后,90.8%的长梗冬青苷被代谢转化为M₂,M₂与铁冬青酸对照品通过HPLC分析时色谱行为一致,故确定M₂为铁冬青酸。结论:长梗冬青苷可以被体外孵育的大鼠肠道菌群代谢转化为铁冬青酸。     

Numerical Analysis of Microcrack Propagation Characteristics and Influencing Factors of Serrated Structural Plane

The serrated structural plane is the basic unit of structural plane morphology. However, the understanding of its internal stress distribution, failure mode and crack evolution law was not clear enough in previous studies. In this paper, the shear mechanical properties of the serrated structural planes were studied by numerical simulation, and the crack evolution law of the serrated structural planes and the effects of four microscopic parameters on the shear properties were analyzed. The results show that: (1) the number of microcracks increases with the increase in normal stress; the crack expansion rate is slow before the shear stress reaches the peak. After the shear stress reaches the peak, the crack expansion rate continues to increase, and the microcracks keep sprouting and expanding, and the number of microcracks tends to stabilize when the shear stress reaches the residual shear strength. (2) The particle contact stiffness ratio kn∗/ks∗ and parallel bond stiffness ratio kn/ks were negatively correlated with the shear strength; and the particle contact modulus E and parallel bond modulus E∗ were positively correlated with the shear strength. As the particle contact modulus E and parallel bond modulus E∗ increase, the peak shear displacement gradually decreases. The parallel bond stiffness ratio kn/ks has a negative correlation with the peak shear displacement. This study is expected to provide theoretical guidance for the microscopic parameter calibration and shear mechanical analysis of serrated structural planes. (3) Several XGBoost, WOA-XGBoost, and PSO-XGBoost algorithms are introduced to construct the quantitative prediction model, and the comparative analysis found that WOA-XGBoost has the best fitting effect and can be used for the prediction of shear strength. When using this model to calculate the weight shares of micro-parameters, it was found that kn∗/ks∗ has the greatest influence on shear strength, followed by E∗; E and kn/ks had the least influence.     

0.05%环孢素A纳米粒滴眼液治疗干眼症的实验研究

目的观察0.05%环孢素A纳米粒滴眼液对干眼症的治疗效果。方法将新西兰兔24只随机分为4组,空白组、阴性对照组、0.05%环孢素A滴眼液组、0.05%环孢素A纳米粒滴眼液组,每组6只。利用东莨菪碱诱导干眼模型,造模成功后开始实验干预:阴性对照组不予处理;0.05%环孢素A滴眼液组及0.05%环孢素A纳米粒滴眼液组分别给与相应滴眼液,3次/天,共持续28天。在干预第1、2、3、4周分别进行Schirmer I(SIT)试验、泪膜破裂时间(BUT)、角膜荧光素染色(CFS)检测。并于干预结束后光镜下观察结膜组织的病理学改变。结果与空白组相比,造模后各干预组泪液分泌量明显减少、泪膜破裂时间显著缩短(P<0.05)。与阴性对照组相比,干预后同时段0.05%环孢素A滴眼液组及0.05%环孢素A纳米粒滴眼液组泪液分泌量增加、泪膜破裂时间延长,干预第1周改善效果最为明显,且0.05%环孢素A纳米粒滴眼液组效果更为显著(P<0.05)。造模后结膜上皮结构紊乱,杯状细胞反应性增多、胞浆丰富,固有层炎性细胞浸润增多。0.05%环孢素A滴眼液组及0.05%环孢素A纳米粒滴眼液组干预4周后,结膜上皮形态排列结构趋于规则,杯状细胞数量减少、胞浆丰富,固有层炎性细胞浸润减少,且0.05%环孢素A纳米粒滴眼液干预效果更为显著。结论0.05%环孢素A纳米粒滴眼液能够有效改善干眼症状,且效果优于传统的0.05%环孢素A滴眼液。     

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.