Objective To investigate the changes of adhesion molecules and their effects on skeletal muscle ischemia/reperfusion injury. Methods 42 Wistar rats were divided into 3 groups: normal control group (Group Ⅰ, n=6), ischemia group (Group Ⅱ, n=6),ischemia/reperfusion injury group (Group Ⅲ, n=30). The level of malondialdehyde (MDA) in the plasma, myeloperoxidase (MPO) in the skeletal muscle, CD11b/CD18 on the leukocytes, intercelluar adhesion molecule-1 (ICAM-1) in the skeletal muscle and the histological changes were studied 1 h, 2 h, 4 h, 8 h, 12 h reperfusion after ischemia for 4 h. Results In group Ⅲ, the expression of CD11b/CD18, ICAM-1 and the injury of skeletal muscle increased with the lapse of reperfusion time. They reached the peak at 8～12 hours' reperfusion. The injury of skeletal muscle developed with the expression of adhesion molecules. Conclusion The expression of CD11b/CD18 and ICAM-1 are significantly associated with the skeletal muscle ischemia-reperfusion injury.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

BACKGROUNDAs a common form of gastric cancer migration, lymph node metastasis largely affects the surgical treatment and prognosis of gastric cancer. Surgery is the fundamental curative option for gastric cancer that varies depending on different stages. The study aimed to compare the clinicopathological characteristics and lymph node metastatic patterns in patients of proximal gastric cancer with different T stages and investigate a reasonable radical gastrectomy approach in terms of the range of lymphadenectomy for proximal gastric cancer.

METHODSIn our retrospective study, the data of 328 patients of proximal gastric cancer with different T stages were analyzed. By comparing the differences of lymph node metastatic rate and ratio, we investigated the clinicopathological characteristics and metastatic patterns of lymph nodes. Also, we were especially interested in the differences in survival rates between patients with and without No. 5 and 6 group metastasis with the same TNM stage.

RESULTSThe overall lymph node metastatic rate and ratio of advanced proximal gastric cancer were 73.4% and 23.3%, respectively. The tumors of different T stages were statistically significant in size and differentiation degree (P < 0.05), multivariate analysis showed that the depth of tumor invasion was an independent risk factor for lymph node metastasis in proximal gastric cancer (RR, 12.025; 95% CI, 2.326 to 62.157; P = 0.003). The overall survival rate of patients with No. 5, 6 group lymph node metastasis and those without was significantly different, but the differences in survival rates between patients with and without No. 5 and 6 group metastasis with the same TNM stage were not statistically significant.

CONCLUSIONSDifferent T stages in proximal gastric cancer showed different patterns and characteristics of lymph node metastasis. D2 lymphadenectomy in patients with early gastric cancer had little survival benefit because metastasis to level 2 nodes was rare. Therefore the range of the lymph node dissection in radical gastrectomy for early gastric cancer was considered reasonable. Moreover, to meet the requirements of the lymph node dissection, total gastrectomy plus D2 lymphadenectomy or more are supposed to be applied for the advanced proximal gastric cancer patients. Precise T staging largely determines the range of gastrectomy and lymphadenectomy.

Aged ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading I-labeled hollow copper sulfide nanoparticles and paclitaxel (I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. F-fluordeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (<0.05) following intra-tumoral (i.t.) injection with I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.