Impact of leukoaraiosis in patients with acute ischemic stroke treated with thrombectomy: a post hoc analysis of the DIRECT-MT trial.

BACKGROUND: The influence of leukoaraiosis in patients with acute ischemic stroke (AIS) given intra-arterial treatment (IAT) with or without preceding intravenous thrombolysis (IVT) remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of IAT in patients with or without leukoaraiosis. METHODS: Patients of the direct mechanical thrombectomy trial (DIRECT-MT) whose leukoaraiosis grade could be assessed were included. DIRECT-MT was a randomized clinical trial performed in China to assess the effect of direct IAT compared with intravenous thrombolysis plus IAT. We employed the Age-Related White Matter Changes Scale for grading leukoaraiosis (ARWMC, 0 indicates no leukoaraiosis, 1-2 indicates mild-to-moderate leukoaraiosis, and 3 indicates severe leukoaraiosis) based on brain CT. The primary outcome was the score on the modified Rankin Scale (mRS) assessed at 90 days. RESULTS: There were 656 patients in the trial, 649 patients who were included, with 432 patients without leukoaraiosis, and 217 (33.4%) patients with leukoaraiosis divided into mild-to-moderate (n=139) and severe groups (n=78). Leukoaraiosis was a predictor of a worse mRS score (adjusted OR (aOR)=0.7 (95% CI 0.5 to 0.8)) and higher mortality (aOR=1.4 (1.1 to 1.9)), but it was not associated with symptomatic intracranial hemorrhage (sICH) (aOR=0.9 (0.5 to 1.5)). IVT preceding IAT did not increase sICH risk for patients with no (aOR=1.4 (0.6 to 3.4)), mild-to-moderate (aOR=1.5 (0.3 to 7.8)), or severe (aOR=1.5 (0.1 to 21.3)) leukoaraiosis. CONCLUSION: Patients with leukoaraiosis with AIS due to large vessel occlusion are at increased risk of a poor functional outcome after IAT but demonstrate similar sICH rates, and IVT preceding IAT does not increase the risk of sICH in Chinese patients with leukoaraiosis.

Novel combined Cre-Cas system for improved chromosome editing in Bacillus subtilis.

To improve the stability and expand applications of genome editing in Bacillus subtilis, we propose a new concept of the Cre-Cas system, which combines Cre-lox72 and CRISPR-Cas9 into an effective and convenient method. Single homologous recombination is used to introduce the integration vector into the chromosome via appropriate guide DNA to inactivate and/or insert genes of interest. The Cre recombinase then removes the region of a selection marker that is no longer needed, and the Escherichia coli replicon between the lox66 and lox71 sites are recombined to a single lox72 site. The CRISPR-Cas9 system can then be applied to remove the inserted foreign gene by targeted cutting. After Cas9 cutting, B. subtilis self-repairs the broken region to its original state without the aid of additional DNA templates. To validate this system, we used T7 and keratinase expression cassettes; self-repair efficiency was evaluated based on the loss or maintenance of the antibiotic resistance gene, as analyzed on selective media. Our results demonstrated that the insertion position in the chromosome is a more critical factor than the insertion length of the gene for efficient self-repair in the B. subtilis genome. This concept can provide the applicability of chromosomal editing in B. subtilis.

MYC Regulates PHF8, Which Promotes the Progression of Gastric Cancer by Suppressing miR-22-3p.

Plant homeodomain finger protein 8 (PHF8) has been reported to participate in cancer development and metastasis of various types of tumors. However, little is known about the functional mechanism of PHF8 in gastric cancer (GC). This study aimed to explore the PHF8 expression pattern and function, and the role of the MYC/miRNA/PHF8 axis in GC. PHF8 expression was upregulated in GC tissues and cells as measured using quantitative reverse transcription polymerase chain reaction and western blotting. PHF8 knockdown suppressed the proliferation, migration, and invasion of GC cells, as determined using the CCK-8 assay and Transwell assay. MicroRNA-22-3p targeted PHF8, as verified by a dual-luciferase reporter assay. MYC upregulated the protein expression of PHF8 but had no effect on PHF8 mRNA expression. MYC regulates PHF8 by affecting the stability of miR-22-3p. We identified a novel MYC/miR-22-3p/PHF8 regulatory axis in GC. Therefore, PHF8 may provide a new therapeutic target for patients with GC.

A Preliminary Study on the Establishment of the PDTX Model.

OBJECTIVE: The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model. MATERIALS AND METHODS: Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients' primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry. RESULTS: The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells. CONCLUSION: A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.

Priority of lymph node dissection for advanced esophagogastric junction adenocarcinoma with the tumor center located below the esophagogastric junction.

To clarify the priority of lymph node dissection (LND) in advanced Siewert type II and III AEG, in which the center of the tumor is located below the esophagogastric junction (EGJ).Data in 395 patients with advanced Siewert type II or III AEG was analyzed retrospectively. The index of estimated benefit from LND (IEBLD) was used to evaluate the efficacy of LND for each nodal station.The mean number of dissected LNs did not differ significantly between patients with type II and III AEG, nor did the mean number of retrieved LNs at each station significantly differ between the 2 groups. According to the IEBLD, the dissection of parahiatal LNs (No.19 and 20) and LNs along the distal portion of the stomach (No.5, 6, and 12a) seemed unlikely to be beneficial, whereas the dissection of Nos.1-3, 7, 9 and 11p yielded high therapeutic benefit (IEBLD>3.0) in both groups. The IEBLDs of No.4d, 8a, and 10 were much higher in type III than in type II AEG cases. No.10 LND may improve survival for type III AEG cases (IEBLD = 2.9), especially for subgroups with primary tumors invading the serosa layer, undifferentiated cancers, macroscopic type 3-4 tumors and tumors ≥50 mm in size (all IEBLDs > 4.0).For advanced AEG located below the EGJ, the dissection of paracardial LNs, lesser curvature LNs, and LNs around the celiac axis would promote higher survival benefits regardless of the Siewert subtype. Patients with type III AEG, especially those with serosa-invasive tumors, undifferentiated tumors, macroscopic type 3-4 tumors and tumors ≥50 mm in size may obtain relatively higher survival benefits from No. 10 lymphadenectomy.

[Clinical analysis of combined organ resection for T4b gastric cancer].

OBJECTIVE: To evaluate the outcomes of combined organ resection for T4b gastric cancer, and determine the operative indication and prognostic factors. METHODS: Clinical data of 96 cases with T4bN0-3bM0 gastric cancer treated with combined organ resection in Tianjin Cancer Hospital from 2001 to 2005 were analyzed retrospectively. RESULTS: Twelve patients developed postoperative complications, including pancreatic fistula (n=4), abdominal infection(n=5), pulmonary infection(n=3), all of which were managed with conservative treatment. There were no perioperative deaths. All the patients had postoperative follow up with a median of 73 months. The 1-, 3-, 5-year overall survival rates were 70.5%, 42.1%, and 23.5%, respectively. Univariate analysis showed that Borrmann type, histologic type, lymph node staging, and pancreatic invasion were associated with the survival in patients with T4b gastric cancer(both P<0.05). Multivariable analysis showed that lymph node staging and histologic type were independent prognostic factors(all P<0.05). CONCLUSION: For well differentiated gastric cancer with lymph node staging of pN0 or pN1, combined organ resection may offer survival benefit.

Pancreatoduodenectomy with vascular reconstruction in treating carcinoma of the pancreatic head.

BACKGROUND: The incidence of carcinoma of the pancreas is increasing in the world. Pancreatic carcinoma is characterized by early local extension to contiguous structures and metastases to regional lymph nodes and the liver. This study was conducted to increase the rate of pancreatoduodenectomy combined with vascular reconstruction. METHODS: Pancreatoduodenectomy with vascular reconstruction was performed for 79 patients at a number of hospitals in Fujian Province, Zhejiang Province, Shanghai and Xinjiang Uyghur Autonomous Region from April 1994 to December 2003. One of these patients also underwent right hemicolectomy; but all received through superior mesenteric vein (SMV)-portal vein (PV) reconstruction. The reconstructions of the superior mesenteric artery (SMA) and hepatic artery (HA) were performed in 4 patients, and reconstructions of the SMA or HA were carried out in 7 and 4 patients respectively. Partial reconstruction of the inferior vena cava (ICV) was done in 2 patients when the tumor was adhering to the wall of the inferior caval vein. RESULTS: Four patients died during the peri-operative period, with a mortality rate of 5%. No complications such as biliary or pancreatic fistulae or artificial blood vessel infection were noted. Histological examination showed one patient with neuroendocrine cancer and the other 78 patients with adenocarcinoma of the pancreatic head. Resected endothelia and vascular margins proved to be microscopically tumor-free. Follow-up for 3 months to 10 years for all except two patients showed 7 of the 9 patients who had undergone resection and reconstruction of the SMA and HA died 7 months or 4 years after operation and 37 survived for over 3 years and 12 for more than 5 years. The rest are still under follow-up. CONCLUSION: Pancreatoduodenectomy with vascular reconstruction for carefully selected patients with carcinoma of the pancreatic head has proved to be a safe and reliable treatment, capable of raising the rates of tumor resection and survival.