BACKGROUND: The therapy of nonunion has been a difficult issue in orthopedics all the time. Part of nonunion can't heal even after many times of operations. The effects of non-surgical treatments are not satisfactory. Extracorporeal shock waves (ESW) is a new method that popular abroad in recent years.OBJECTIVE: To investigate the effect of ESW on nonunion, and preliminarily probe into its mechanism.DESIGN: Randomized group-division design, animal experiment.SETTING: Department of Orthopedics, Renmin Hospital of Wuhan University.MATERIALS: The experiment was conducted in the Medical Experimental Center of Animal, Wuhan University from September 1997 to March 1999. Forty healthy male rabbits were selected to establish model of nonunion. Thirty-two rabbits with hypertrophic nonunion were taken as materials and randomly divided into treatment group and control group with 16 rabbits in each group.METHODS: A multifunctional ESW apparatus of type HX902Ⅲ was adopted to treat the broken ends of nonunion in the treatment group with the energy, frequency, dose and focus range of 0.54 m J/mm2, 60 times/minute,2 000 times and 1.5 cm2 respectively. The second focus of shock wave was adjusted, aiming at corresponding parts in distal and proximal sites of nonunion, and acted 1 000 times. After that, rabbits were re-fixed with external apparatus and acted freely. Rabbits in the control group were fixed with external apparatus without any other treatments.MAIN OUTCOME MEASURES: Examination of the healing of nonunion with radiograph, transmission electron microscope (TEM) and in histology.RESULTS: A total of 32 enrolled animals were involved in the analysis of results.①X-ray photograph: During the treatment with ESW, the gaps of nonunion were more and more indistinct in X-rays, and the densities of two sclerotic ends were reduced, and the sclerotic marrow cavities became unobstructed. The X-rays of nonunion-gaps before ESW were significantly narrowed than those after the treatment. At 6 weeks after the treatment,nonunion in 6 rabbits of the treatment group (6/14) healed, and that in 12 animals (12/12) healed on the 12th week. However, only the nonunion in one rabbit (1/12) healed in the control group on the 12th week. Test of fourfold-table exact probability demonstrated that the healing status of nonunion in the treatment group was better than the control group, and the differences were remarkable (P＜0.001).②Examination under light microscope: large quantity of osteoblasts and mesenchymal cells assembled and were active in proliferation on the 2nd week of treatment in the treatment group, and plentiful bone trabeculae formed on the 6th week, and the nonunion healed on the 12th week of treatment. However, there were chronic inflammation and few trabeculae in the control group. ③TEM examination: the osteoblasts in the treatment group proliferated on the 2nd week of treatment, and there were abundant chondrosomes in the intracytoplasm,which could secrete collagen fibers with periodical transverse lines. On the 6th week, large amount of bone lacunas formed. However, little visible cells could be seen in the control group, and osteoclasts were found in act.CONCLUSION: The effect of ESW on hypertrophic nonunion is satisfactory, which may become a reliable and non-invasive treatment of nonunion.

Objective To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in intrathoracic tuberculosis(TB).Methods We retrospectively analyzed patients underwent EBUS-TBNA with a final diagnosis of intrathoracic TB at Shanghai Chest Hospital from October 2009 to March 2013 and observed that the diagnostic efficacy by pathology and microbiology and safety of EBUS-TBNA for intrathoracic TB.Results 75 patients were diagnosed with pulmonary TB or intrathoracic tuberculous lymphadenitis,and accuracy was 80％ (60/75) by EBUS TBNA.A total of 60 patients had pathology,acid-fast bacilli(AFB) staining and mycobacterial culture test results,of whom 52 (86.67％)were diagnosed.Pathological findings were consistent with TB in 77.33％ patients (58/75),in 20.31％ (13/64) the smear were positive for AFB and in 46.67％ (28/60) were positive for cuhure.One hundred and twenty-nine mediastinal or hilar lymph nodes and 10 intrapulmonary lesions were biopsied in 75 patients,the average target number of per patient were 1.85.Pathological findings were consistent with TB in 66.19％ samples(92/139),in 13.91％ (16/115) were positive for AFB and in 38.32％ (41/107) were positive for culture.Multivariate regression revealed that short-axis diameter was an independent risk factor associated with positive pathology,smear and euhure.Additionally,more aspiration times cause higher pathology positive rate,pathology showing necrosis and positive smear were independent risk factors associated with positive cuhure.There were two patients occurred complications during operation.Conclusion EBUS-TBNA was a safe and effective method for the diagnosis of intrathoracic tuberculosis.

PURPOSE: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. MATERIALS AND METHODS: Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed. RESULTS: The AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival. CONCLUSION: A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; China ; Estrogens ; Exons ; Humans ; Mutation Rate ; Phenotype ; Prevalence* ; Prognosis ; Prospective Studies ; Receptor, Epidermal Growth Factor

OBJECTIVETo explore the relationship between the time after thrombosis and the efficacy of combined ultrasound and microbubble treatment for rescuing the ischemic tissues.

METHODSRat models of thrombosis in the right common iliac artery were established and received combined ultrasound and microbubble treatment at 3, 6 and 12 h after thrombosis. The recanalization rate of the right common iliac artery was assessed using both 2-dimensional and Doppler ultrasound. The plateau acoustic intensity (AI) was quantified for estimating the skeletal microvascular blood volume, and skeletal muscle injury markers including myoglobin (Mb) and creatinine kinase (CK) were measured using ELISA. Postmortem TUNEL staining was used to detect the apoptotic rate of skeletal muscle cells in the hind limb of the rats.

RESULTSCompared with those in 3 h group, the recanalization rate and AI were significantly lower, and the levels of Mb and CK and the apoptotic rate of the skeletal muscle cells were significantly higher in both 6 h group and 12 h group ( < 0.05). Compared with those in 6 h group, the rats receiving treatment at 12 h after thrombosis showed significantly lowered AI and increased Mb, CK and apoptotic rate of the skeletal muscle cells ( < 0.05).

CONCLUSIONSThe efficacy of combined ultrasound and microbubble treatment for rescuing ischemic tissues tends to be attenuated as the time after thrombosis prolongs in rats.

During early embryonic development, cell fate commitment represents a critical transition or "tipping point" of embryonic differentiation, at which there is a drastic and qualitative shift of the cell populations. In this study, we presented a computational approach, scGET, to explore the gene-gene associations based on single-cell RNA sequencing (scRNA-seq) data for critical transition prediction. Specifically, by transforming the gene expression data to the local network entropy, the single-cell graph entropy (SGE) value quantitatively characterizes the stability and criticality of gene regulatory networks among cell populations and thus can be employed to detect the critical signal of cell fate or lineage commitment at the single-cell level. Being applied to five scRNA-seq datasets of embryonic differentiation, scGET accurately predicts all the impending cell fate transitions. After identifying the "dark genes" that are non-differentially expressed genes but sensitive to the SGE value, the underlying signaling mechanisms were revealed, suggesting that the synergy of dark genes and their downstream targets may play a key role in various cell development processes.The application in all five datasets demonstrates the effectiveness of scGET in analyzing scRNA-seq data from a network perspective and its potential to track the dynamics of cell differentiation. The source code of scGET is accessible at https://github.com/zhongjiayuna/scGET_Project.