Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

Efficiency of ectopic thymectomy by three surgical approaches in non-thymomatous myasthenia gravis.

BACKGROUND: To explore the efficiency of ectopic thymectomy by the three surgical approaches of trans-sternum, right unilateral thoracoscopy and thoracoscopic subxiphoid in patients with non-thymomatous myasthenia gravis. METHODS: 155 consecutive non-thymomatous myasthenia gravis patients who underwent extended thymectomy by 3 approaches including trans-sternum, right unilateral thoracoscopy and thoracoscopic subxiphoid in 1st affiliated hospital of Sun Yat-Sen University from January 2017 to October 2019 were reviewed. Differences of perioperative clinical characteristics in three surgical approaches were analyzed. RESULTS: Time to onset of myasthenia gravis (early or late) (p = 0.018), blood loss (p < 0.001), duration of operation (p = 0.031), duration and volume of thoracic drainage (p = 0.039 and p = 0.026), length of hospitalization (p = 0.039), the efficiency of ectopic thymectomy (p = 0.037), and the detection rate of ectopic thymus in the second quadrant (p = 0.018) were different among the three surgical approaches. In univariate logistic regression analysis, higher efficiency of ectopic thymectomy were associated with transsternal (OR 2.36, 95% CI 1.32-4.22, p = 0.011) and thoracoscopic subxiphoid approaches (OR 2.07, 95% CI 1.12-3.82, p = 0.033). In the multiple logistic regression analysis, the transsternal approach (OR 2.02, 95% CI 1.10-3.71, p = 0.024) was an independent protective factor for the efficiency of ectopic thymectomy. CONCLUSIONS: Both the right unilateral thoracoscopic and thoracoscopic subxiphoid approaches have advantages over the transsternal approach in short-term postoperative recovery. Transsternal approach is still the best choice for ectopic thymectomy while thoracoscopic subxiphoid approach show the potential as an alternative way.

miR-204-5p inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by regulating Nestin.

Esophageal cancer (EC) is a highly malignant gastrointestinal tumor, and esophageal squamous cell carcinoma (ESCC) is one of the most common histological types of EC. MicroRNAs (miRNAs) are small noncoding RNAs closely related to tumorigenesis and tumor progression. In addition, Nestin is an intermediate filament protein (class VI) and contributes to the progression of numerous tumors. However, the correlation between miRNAs and Nestin in ESCC remains unclear. This study aimed to investigate the relationship between miR-204-5p and Nestin in ESCC. First, Nestin-related miRNAs in ESCC were explored using RNA sequencing. In ESCC tissues and cell lines, the expression of miR-204-5p was decreased detected by quantitative real-time polymerase chain reaction (qPCR), whereas Nestin protein level was upregulated identified by Western blotting (WB). Besides, Nestin was the direct target of miR-204-5p in ESCC determined via the luciferase reported assay. Moreover, miR-204-5p regulated Nestin to inhibit ESCC cell proliferation detected by the colony formation assay and promote ESCC cell apoptosis identified using the flow cytometry and TUNEL assay. Furthermore, miR-204-5p suppressed tumorigenesis in vivo evaluated by the murine xenograft tumor model. In conclusion, these results indicated that miR-204-5p inhibited cell proliferation and induced cell apoptosis in ESCC through targeting Nestin, which might provide novel therapeutic targets for ESCC therapy.

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer.

Background: Evidence of the efficacy of immune checkpoint inhibitors (ICIs) plus antiangiogenic drugs in previously treated patients with advanced non-small-cell lung cancer (NSCLC) is still insufficient, so we investigated the safety and efficacy of nivolumab plus recombinant human (rh)-endostatin in such patients. Methods: Patients without epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) targetable mutations in advanced NSCLC who did not respond to previous treatment were enrolled. Eligible patients received nivolumab (3 mg/kg, i.v. drip, day 1) every 2 weeks and rh-endostatin (210 mg, continuous i.v. infusion for 168 h) every 4 weeks until disease progression or discontinuation. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), clinical benefit response rate (CBR), progression-free survival (PFS), overall survival (OS) and safety. Results: A total of 34 patients received a median of 4 cycles of therapy. In all, 14 patients achieved confirmed partial response (PR) with an ORR of 41.2% [14/34; 95% confidence interval (CI): 23.7-58.6%], DCR of 64.7% (22/34; 95% CI: 47.8-81.6%), CBR of 44.1% (95% CI: 26.5-61.7%), and a DOR of 6.9 (95% CI: 4.4-9.4) months. Median follow-up was 12.2 (range, 2.3-18.1) months. Median PFS (mPFS) was 6.8 (95% CI: 1.1-12.1) months, median OS (mOS) was 17.1 (95% CI: 6.6-27.6) months, and 12-month survival rate of 64.4% (95% CI: 46.2-82.6%). In all, 18 (18/34, 52.9%) patients experienced at least one treatment-related adverse event (TRAE), and Grade 3 TRAEs occurred in 4 (4/34, 11.8%) of them. Conclusions: This study is first to assess nivolumab plus rh-endostatin in previously treated patients with advanced NSCLC. In view of its favorable efficacy and safety profile, this combination represents a promising treatment regimen in this patient population.

A Child Infected with COVID-19 in China-A Case Report.

A 16-month-old boy was admitted with cough for 2 days and fever for 1 day. Chest computed tomography (CT) scan of the child revealed large areas of ground-glass opacities in both lungs. Nucleic acid amplification tests (NAATs) were performed repeatedly to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the results were all negative. On day 13 of hospitalization, no clinical symptoms except diarrhea were present in the patient, and re-examination by chest CT revealed lesion shrinkage, but the NAAT on throat swabs was positive. On day 22 of hospitalization, the NAAT on throat swabs was negative and the fecal samples were positive. Positive fecal samples nucleic acid lasted for 62 days. Suggesting that pediatric patients may be important sources of infection during the recovery phase of clinical symptoms and whether SARS-CoV-2 has fecal-oral transmission needs further study.

Treatment Patterns and Survival of Patients With Advanced Non-Small Cell Lung Cancer Guided by Comprehensive Genomic Profiling: Real-World Single-Institute Study in China.

Although the National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology guidelines recommend comprehensive genomic profiling of lung adenocarcinoma, it has not been widely applied in Chinese hospitals. This observational study aimed to determine real-world evidence of whether comprehensive genomic profiling can benefit the survival of patients with lung cancer. We investigated the frequency of genomic alterations, treatment strategies, and clinical outcomes in 233 patients with advanced non-small cell lung carcinoma who were routinely screened using a 508-gene panel. The most prevalent drivers were mutations of EGFR (51%), KRAS (9%), PIK3CA (7%), ALK (7%), MET (6%), and BRAF (5%). Mutations in tumor suppressor genes included TP53, KEAP1, RB1, PTEN, and APC. Median overall survival (OS) was significantly shorter among patients harboring KRAS (mutant, n = 17; WT, n = 154) and TP53 (mutant, n = 103; WT n =68) mutations (11.3 vs. 24.0 months; P = 0.16 and 18.7 vs. 28.7 months; P = 0.018, respectively). The OS was longer among patients with tumors harboring EGFR (P = 0.069) and ALK (P = 0.51) mutations. Most patients (65.4%) with the driver gene-positive (EGFR, ALK, and ROS1) tumors were received TKI treatment, whereas those with driver gene wild tumors (53.1%) chose platinum-based therapy. Univariate and multivariate analyses associated a shorter OS among patients with tumors harboring concomitant TP53 and EGFR mutations. These findings provide additional evidence from real-world on the potential importance of targeted therapies as a treatment option in NSCLC patients harboring clinically actionable mutation.

A Single-Center, Cross-Sectional Study of Children with Steroid-Resistant Nephrotic Syndrome in Southern China.

INTRODUCTION: We conducted a cross-sectional study on children with steroid-resistant nephrotic syndrome (SRNS) in a single center in Southern China. METHODS: A total of 166 SRNS cases in the Paediatric Nephrology Center of the First Affiliated Hospital of Sun Yat-Sen University from September 1, 2006, to August 31, 2016 were retrospectively analysed. The inclusion criteria were: 1) age ≤ 14 years, 2) diagnosed with SRNS, and 3) without purpura nephritis, immunoglobulin A nephropathy, lupus nephritis, or another secondary nephritis. Incidences of primary/ late steroid-resistance and curative effects were analysed. RESULTS: The median follow-up time was 4.64 (2.64 to 8.11) years. There were 67 cases of complete remission (CR) (40.36%), 46 cases of partial remission (PR) (27.71%), 31 cases of no remission (NR) (18.67%), 18 cases of end-stage renal disease (ESRD, 10.84%, including 7 cases of kidney transplantation), and 4 cases of death due to hematoma and severe infection after renal biopsy; renal failure after progression to ESRD; sepsis during glucocorticoid (GC) + Cyclosporine A (CsA) treatment; and multiple organ failure at the onset of disease, respectively. For the 8 cases with gene mutation, unnecessary drug treatment should be reduced due to their low responsiveness to immunosuppressive treatment. Female, patients with hematuria, primary steroid-resistance (PSR) type and histopathologic focal segmental glomerulosclerosis (FSGS) were more likely to have higher ESRD rate. Subgroup analysis of ESRD suggested that female patients and patients with PSR type were more likely to develop ESRD. Cox-regression analysis showed that female (HR = 3.04, 95% CI: 1.18 to 7.86; P < .05), without hematuria (HR = 0.36, 95% CI: 0.14 to 0.91; P < .05), and LSR type (HR = 0.17, 95% CI: 0.04 to 0.74; P < .05) were significantly associated with ESRD. Kaplan-Meier survival analysis also showed the same trends. CONCLUSION: Of the 166 SRNS cases, 68.07% of patients achieved CR or PR, 18.67% of cases had NR, 10.84% of cases developed ESRD, and 2.41% of patients died during follow-up. Female gender, hematuria, and PSR type were positively associated with ESRD.

Relationship of possible biomarkers with malignancy of thymic tumors: a meta-analysis.

BACKGROUND: Role of biomarkers for promotion of tumor proliferation (BPTPs) and for promotion of apoptosis (BPAs) in thymic malignant tumors is still unclear. The purpose of this study was to evaluate the relationship between BPTPs and/or BPAs and malignancy of thymic malignant tumors. METHODS: Studies on thymic malignant tumors and biomarkers were searched in PubMed, ISI Web of Knowledge, and Embase databases, and all statistical analyses were conducted using Review Manager. RESULTS: Twelve articles related to biomarkers and thymic malignant tumors were selected and analyzed. A relationship between BPAs and Masaoka stage was demonstrated for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 138 stage I/II patients and 74 stage III/IV patients, and BPAs were significantly correlated with high Masaoka staging (P = 0.03). We further found a relationship between BPAs and degree of malignancy for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 176 thymoma patients and 36 thymic carcinoma patients, and BPAs were significantly correlated with thymic carcinoma (P = 0.010). In addition, a relationship between BPTP and Masaoka staging was demonstrated for seven markers, namely Podoplanin, Glut-1, Muc-1, Egfr, Igf1r, c-Jun, and n-Ras, included 373 patients with stage I/II and 212 patients with stage III/IV, and BPTPs were significantly correlated with high Masaoka staging (P < 0.001). We also found a relationship between BPTPs and degree of malignancy for ten markers, namely Mesothelin, c-Kit (CD117), Egfr, Lat-1, Muc-1,Ema, Glut-1, Igf1r, c-Jun, and n-Ras, included 748 thymoma patients and 280 thymic carcinoma patients, and BPTPs were significantly correlated with thymic carcinoma (P < 0.001). CONCLUSION: These findings show that high levels of BPTPs or BPAs are more closely related to thymic carcinoma and Masaoka stage III/IV, suggesting that BPTPs and BPAs may play an important role in the occurrence and development of thymic malignant tumors.

Long Non-Coding RNA (lncRNA) CRNDE Regulated Lipopolysaccharides (LPS)-Induced MRC-5 Inflammation Injury Through Targeting MiR-141.

BACKGROUND Pneumonia is a common disease with high morbidity and even death. In our country, pneumonia is the leading cause of child death. Therefore, research on the pathogenesis of pneumonia can help improve the treatment of pneumonia. Long non-coding RNA (lncRNA) is an important regulator of disease development, and its regulatory mechanism is closely related to cellular processes. However, the function and regulatory network of lncRNA is not fully elucidated in pneumonia. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of CRNDE and miR-141 in lipopolysaccharides (LPS)-induced MRC-5 cells and pneumonia tissues. MTT (3-(4,5-dimethylthiazol-2-yl)-2 5-diphenyl-2-tetrazolium) assay was used to assess cell proliferation. Flow cytometry assay was performed to detect cell apoptosis in LPS-induced MRC-5 cells. Enzyme-linked immunosorbent assay and western blot were used to measure the levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-alpha, respectively. In addition, luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to prove the relationship between CRNDE and miR-141. RESULTS In this study, we found that CRNDE expression was induced in LPS-induced MRC-5 cells and pneumonia tissues. Moreover, miR-141 expression was low in LPS-induced MRC-5 cells and was verified was a target miRNA of CRNDE by using luciferase reporter assay and RIP assay. The downregulation of CRNDE and upregulation of miR-141 promoted cell viability, inhibited cell apoptosis, as well as decreased the levels of IL-1ß, IL-6, and TNF-alpha. Moreover, we demonstrated that si-CRNDE transfection increased cell viability and suppressed cell apoptosis and the levels of IL-1ß, IL-6, and TNF-alpha, which were alleviated by anti-miR-141 transfection in LPS-induced MRC-5 cells. CONCLUSIONS In this study, we found that downregulation of CRNDE and upregulation of miR-141 inhibited cell apoptosis and inflammation response and promoted cell viability in LPS-induced MRC-5 cells. Low CRNDE expression increased cell growth and suppressed inflammation response, which was impaired by inhibition of miR-141. These results suggested that a novel therapeutic target was found in pneumonia treatment.

Postoperative intensity-modulated radiation therapy reduces local recurrence and improves overall survival in III-N2 non-small-cell lung cancer: A single-center, retrospective study.

PURPOSE: To determine the postoperative effects of radiotherapy (PORT) on the local recurrence-free survival (LRFS) and overall survival (OS) of stage III-N2 non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: 183 patients with resected stage III-pN2 NSCLC from Hunan Cancer Hospital between 2013 and 2016 were divided into two groups for postoperative chemotherapy (POCT) (n = 105) or combination chemotherapy and radiotherapy (POCRT) (n = 78). The LRFS and OS were compared and the factors affecting local recurrence were illustrated in these two groups. The sites of failure based on the lobe of the primary tumor in two groups were described. RESULTS: PORT leads to a strikingly lower risk for local recurrence and brought superior OS benefit. For different pN2 Subclassification, Patients with multiple-station pN2 ± pN1 disease had the worst LRFS (11 months) and single-station pN2 + multiple station pN1 disease had a relatively short LRFS (24 months) in group POCT. Short LRFS is correlated with multiple-station pN2, older age (Y > 55), patients with a high positive LN ratio > 1/3 and a poor tumor histological differentiation degree. In group POCT, the most frequent failure site occurs at the ipsilateral hilum (21.0%), the bronchial stump (20.0%), followed by LNs4R (19.0%), LNs4L (18.1%), LNs7 (15.2%), most of left-sided tumors more frequently involved the contralateral mediastinum, whereas the ipsilateral recurrences dominated for right-sided tumors, especially for LNs4R. In group POCRT, the highest failure site was the bronchial stump (11.5%), followed by LNs4L (8.97%), LNs1 (7.69%), the ipsilateral hilum (6.41%) and LNs4R (6.41%). CONCLUSION: PORT remarkably reduced local recurrence and improved OS in stage III-pN2 NSCLC, especially in the multiple-station pN2 group.

Lymphadenectomy Along Bilateral Recurrent Laryngeal Nerves Under Single-Incision Mediastinoscopy.

This report proposes an approach for lymphadenectomy along bilateral recurrent laryngeal nerves (RLNs) under mediastinoscopy through a single left-neck incision. After pneumomediastinum is established, esophagectomy is begun over the aortic arch to the level of the lower edge of the left main bronchus, and lymphadenectomy along the left RLN is also accomplished. At the level of the lower edge of the right subclavian artery, between the trachea and the esophagus, the instruments can gain access to the right RLN. The lymphadenectomy may be performed up to 2 cm above the upper edge of the right subclavian artery.

Mediastinal lymphadenectomy under laparoscopic assisted single-port inflatable mediastinoscopy through left neck approach.

Minimally invasive esophagectomy (MIE) has been developed for decades. However, conventional MIE requires transthoracic surgery, which can increase the risk of many perioperative cardiopulmonary complications. Therefore, mediastinoscopy-assisted transhiatal esophagectomy has been proposed, but the traditional surgical methods have shortcomings, such as unclear vision, especially during the dissection of mediastinal lymph nodes (LNs). A new approach for mediastinal lymphadenectomy under single-port inflatable mediastinoscopy with one left-neck incision is proposed. There are three difficulties in this procedure. (I) LNs along the left recurrent laryngeal nerve (RLN). After establishing pneumomediastinum, esophagectomy is performed over the aortic arch to the level of the lower edge of the left main bronchus, and lymphadenectomy along the left RLN is also accomplished during this process. (II) LNs along the right RLN. At the level of the lower edge of the right subclavian artery (RSA), between the trachea and the esophagus, instruments are used to access the right RLN. Lymphadenectomy of up to 2 cm can be accomplished at the upper edge of the RSA. (III) Subcarinal LNs. Between the trachea and esophagus, the left and right main bronchi are exposed along the trailing edge of the trachea down to the carina, and lymphadenectomy can be performed here. The surgical procedure described here in detail is the first mediastinal lymphadenectomy under mediastinoscopy with one single left-neck incision.

Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery for Radical Esophagectomy Is an Effective and Safe Treatment for Esophageal Cancer.

BACKGROUND: We previously developed a novel non-trans thoracic esophagectomy, the single-port inflatable mediastinoscopy combined with laparoscopy for the radical esophagectomy of esophageal cancer. The purpose of this study was to report its therapeutic efficacy and safety. METHODS: From May 2016 to August 2017, we have completed 80 cases of radical resection of esophageal carcinoma using this novel surgical technique. The intraoperative findings and postoperative complications were reported. RESULTS: The operation was successfully performed in all patients except for one patient switched from laparoscopic-assisted operation to open surgery. The mean operation duration was 191.4 ± 27 min, and the mean intraoperative blood loss was 147.3 ± 28.9 mL. The mean number of removed lymph node was 21.9 ± 4.1. Five patients (6.4%) who had preoperative type I respiratory failure needed to stay in the intensive care unit for 24 h postoperatively. Postoperative complications included anastomotic leakage (8.9%), anastomotic stricture (21.25%), pleural effusion (9%), and hoarseness postoperative hoarseness (18.8%). The incidence of hoarseness at 3 months postoperation was reduced to 3.8%. All the complications were Clavien-Dindo grades I-III. There were no perioperative death and postoperative cardiopulmonary complications. CONCLUSION: These results showed that the single-port inflatable mediastinoscopy combined with laparoscopy is feasible for radical esophagectomy and possesses good therapeutic efficacy and safety.

Mesenchymal Stromal Cells-Derived ß2-Microglobulin Promotes Epithelial-Mesenchymal Transition of Esophageal Squamous Cell Carcinoma Cells.

Mesenchymal stromal cells (MSCs) have been considered as one of the pivotal type of cells composing the tumor microenvironment. Although contact-dependent mechanisms and paracrine factors are thought to collaborate in governing the MSCs-based effects on tumors progression, the underlying mechanisms remain largely unknown. In particular, the involvement of MSCs-derived cytokines in the epithelial-mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) has not been clarified. In this study, we observed that ß2-Microglobulin (B2M) is highly expressed in MSCs but scarcely in ESCC cells. Based on the previously described EMT promoting effect of B2M, we investigated the in vitro effect of MSCs-derived B2M on the EMT of ESCC cells, and discovered its subsequent enhancing effects on cell mobility and tumor-initiation. Further xenograft transplantation experiments confirmed the in vivo induction of tumor-initiation by MSCs-derived B2M. Noteworthy, we showed that the B2M expression positively correlated with poor prognosis. The fact that B2M is primarily expressed by the stroma of the ESCC tissue strengthens our hypothesis that in ESCC, MSCs-derived B2M promotes tumor-initiation and invasion via enhancing EMT, resulting in an adverse prognosis for the patients. Our results will be valuable for the prediction of the development and treatment of ESCC.

Expression of periostin in small cell lung cancer and its effect on chemoresistance / 中国胸心血管外科临床杂志

@#Objective    To detect the difference of periostin expression in small cell lung cancer (SCLC) cell, and explore its effect on chemoresistance of SCLC patients. Methods    The expression of periostin in mRNA and protein was detected by RT-PCR and Western blot analysis in SCLC H69 and multidrug resistant strain H69AR. The expression of periostin was up-regulated by recombinant plasmid-periostin in H69 cell. The survival rate in the transfected group was different from that of the negative control group and uninterrupted group. Results    The expression of periostin mRNA and protein in the sensitive strain H69 was lower than that of the multidrug resistant strain H69AR (P<0.05). The recombinant periostin-plasmid was transfected into H69 cells and at the same concentration of chemotherapeutic drugs (cisplatin, etoposide) the survival rate increased significantly (P<0.05). The positive expression rate of periostin in SCLC tissues was 67.44%, and the sensitivity of the chemotherapy group was lower than that of the drug resistant group (P<0.05). Conclusion    The expression of periostin in SCLC cell H69 is significantly lower than that of the multidrug resistant strain H69AR and overexpression of periostin increases resistance of the sensitive strain H69 and hence periostin may be involved in SCLC chemoresistance.

MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). We found significantly more positively expressed CTGF protein in ESCC tissues was than in normal adjacent esophageal tissues (P<0.01). Dual luciferase reporter gene assay showed that miR-145 can specifically bind with the 3'UTR of CTGF and significantly inhibit the luciferase activity by 55% (P<0.01). Up-regulation of miR-145 or down-regulation of CTGF can suppress the proliferation, migration, invasion, and EMT process of ESCC cells. CONCLUSIONS MiR-145 was significantly down-regulated in ESCC tissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

Preoperative Anxiety in Patients With Myasthenia Gravis and Risk for Myasthenic Crisis After Extended Transsternal Thymectomy: A CONSORT Study.

A thymectomy can ameliorate the symptoms of myasthenia gravis (MG) and prevent the progression of ocular MG (OMG) to generalized MG (GMG). However, postoperative myasthenic crisis (POMC) is a serious post-thymectomy complication. Preoperative anxiety (POA) is common but typically neglected in MG patients. The association of POA with POMC has not yet been examined.From June 2007 to December 2013, 541 cases of MG were admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). All cases underwent extended transsternal thymectomy (ETT). The clinical and pathological characteristics of these patients, including POA and POMC, were analyzed.A total of 179 patients experienced POA and 67 patients experienced POMC. Patients with POA were more likely to have POMC, a thymoma, and an ectopic thymus. Univariate analysis showed that POMC correlated with POA, presence of an ectopic thymus, dose of pyridostigmine bromide (PYR), presence of a thymoma, MGFA stage, preoperative myasthenic crisis, and postoperative pneumonia. Multivariate logistic regression analysis showed that the independent risk factors for POMC were POA, preoperative myasthenic crisis, higher dose of PYR, and postoperative pneumonia.Our results suggest that clinicians should consider the risk factors for POMC-especially preoperative anxiety-before performing a thymectomy in patients with MG.

Antiapoptotic Effect of Recombinant HMGB1 A-box Protein via Regulation of microRNA-21 in Myocardial Ischemia-Reperfusion Injury Model in Rats.

The ~80 amino acid A box DNA-binding domain of high mobility group box 1 (HMGB1) protein antagonizes proinflammatory responses during myocardial ischemia reperfusion (I/R) injury. The exact role of microRNA-21 (miR-21) is unknown, but its altered levels are evident in I/R injury. This study examined the roles of HMGB1 A-box and miR-21 in rat myocardial I/R injury model. Sixty Sprague-Dawley rats were randomly divided into six equal groups: (1) Sham; (2) I/R; (3) Ischemic postconditioning (IPost); (4) AntagomiR-21 post-treatment; (5) Recombinant HMGB1 A-box pretreatment; and (6) Recombinant HMGB1 A-box + antagomiR-21 post-treatment. Hemodynamic indexes, arrhythmia scores, ischemic area and infarct size, myocardial injury, and related parameters were studied. Expression of miR-21 was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify apoptosis. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of pressure rise (+dp/dtmax), and decline (-dp/dtmax) showed clear reduction upon treatment with recombinant HMGB1 A-box. Arrhythmia was relieved and infarct area decreased in the group pretreated with recombinant HMGB1 A-box, compared with other groups. Circulating lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels increased in response to irreversible cellular injury, while creatine kinase MB isoenzymes (CK-MB) and superoxide dismutase (SOD) activities were reduced in the I/R group, which was reversed following recombinant HMGB1 A-box treatment. Interestingly, pretreatment with recombinant HMGB1 A-box showed the most dramatic reductions in miR-21 levels, compared with other groups. Significantly reduced apoptotic index (AI) was seen in recombinant HMGB1 A-box pretreatment group and recombinant HMGB1 A-box + antagomiR-21 post-treatment group, with the former showing a more dramatic lowering in AI than the latter. Bax, caspase-8, and CHOP showed reduced expression, and Bcl-2 and p-AKT levels were upregulated in recombinant HMGB1 A-box pretreatment group. Thus, recombinant HMGB1 A-box treatment protects against I/R injury and the mechanisms may involve inhibition of miR-21 expression.

Relationship of Oct-4 to malignant stage: a meta-analysis based on 502 positive/high Oct-4 cases and 522 negative/low case-free controls.

BACKGROUND: Octamer 4 (Oct-4), an important member of the POU domain transcription factor family, has been suggested to function as a master switch during differentiation of human somatic cells and more recently has come to be linked with neoplastic properties. The aim of this study was to evaluate the relationship between Oct-4 and cancer stage using a meta-analysis approach. MATERIALS AND METHODS: Relevant articles published as of May 2015 were retrieved from the following databases: PubMed, ISI Web of Knowledge, Embase, and Chinese National Knowledge Infrastructure (CNKI). The strengths of relationship for outcomes of interest were estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 11 articles on Oct-4 and cancer staging that collectively included 502 positive/high Oct-4 cases and 522 negative/low case-free controls were chosen. Positive/high Oct-4 was significantly associated with cancer stage in several kinds of cancer. Specifically, positive/high Oct-4 was associated with cancer stage III/IV (fixed effects: OR = 1.53, 95% CI = 1.12-2.10), primary tumor (T3-4) (random effects: OR = 1.93, 95% CI = 0.99-3.77), and cancer grade of differentiation (intermediate-poor) (random effects: OR = 3.45, 95% CI = 1.5-7.61). CONCLUSIONS: These findings suggest that positive/high Oct-4 is more strongly linked to stage III/IV cancer and cancer grade of differentiation, and is correlated with malignant characteristics that lead to poor prognosis in different types of cancer, especially in Asian. Given variability related to ethnicity and differences in cancer types, additional studies are warranted to establish the generalizability of our findings.

Specific Safety Profile of Bevacizumab in Asian Patients With Advanced NSCLC: A Meta-Analysis.

Randomized studies have obtained varying findings regarding the benefits and toxicities of bevacizumab in the treatment of nonsmall cell lung cancer (NSCLC). It is unclear whether the discrepancies among trials are due to ethnic/racial differences. We therefore performed a meta-analysis of all published, randomized, controlled clinical trials involving bevacizumab in patients with NSCLC to assess its effectiveness and safety in Asian and non-Asian populations. Results from the phase II JO19907 trial, the phase III AVAiL and ECOG 4599 trials, and the phase IV SAiL trials were used to calculate the benefits and toxicities of bevacizumab in Asian and non-Asian patients. Combined statistical estimates, including hazard ratios and odds ratios, were calculated using fixed-effects and random-effects models. A total of 4308 patients were evaluated. Combining bevacizumab with different chemotherapy regimens resulted in similar objective response rates, overall survival, and progression-free survival in Asian and non-Asian populations. Disease control rates, however, were only reported in Asian populations. The rates of severe bleeding (relative risk [RR], 2.17; P = 0.02) and thromboembolism (RR, 3.65; P < 0.0001) were significantly higher, while the rate of severe proteinuria was significantly lower (RR, 0.43; P < 0.0001), in non-Asian than in Asian populations. The rates of severe hypertension (P = 0.71) and hemoptysis (P = 0.66) were similar in Asian and non-Asian populations. Bevacizumab combined with chemotherapy for first-line NSCLC treatment showed similar benefits in Asian and non-Asian populations, but had specific safety profiles in each.