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2.
Mol Ther Nucleic Acids ; 17: 578-589, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31382189

RESUMO

Spinal cord injury (SCI) is a devastating medical condition, often accompanied by motor and sensory dysfunction. The Hedgehog (Hh) pathway has a protective role in pathological injury after SCI. However, the specific mechanism remains unclear. The present study aimed to confirm the effects of the mitogen-activated protein kinase kinase-2 (MEKK2)/MEKK3/JNK/Hh pathway on SCI. SCI rat models were established and then inoculated with plasmids overexpressing MEKK2/MEKK3 or with small interfering RNA (siRNA) against MEKK2/MEKK3. The expression of MEKK2 and -3 was detected in dorsal root ganglia (DRG) cells. The motor function of hindlimbs, the expression of the c-Jun N-terminal kinase (JNK)- and Hh-pathway-related genes, and the level of neurofilament-200 (NF-200) and glial fibrillary acidic protein (GFAP) were measured. MEKK2 and -3 were expressed at a high level in DRG cells. The silencing of MEKK2/MEKK3 in rats caused an increase in the expression of glioma-associated oncogene homolog-1 (Gli-1), Nestin, smoothened (Smo), and Sonic Hedgehog (Shh). The Basso, Beattie, and Bresnahan (BBB) rating and the level of NF-200 protein also increased. However, the expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1ß (MIP-1ß), MIP-3α, p-JNK/JNK, and p-c-Jun/c-Jun and the level of GFAP were reduced. Downregulation of MEKK2/MEKK3 ameliorated the symptoms of SCI by promoting neural progenitor cell differentiation via activating the Hh pathway and disrupting the JNK pathway. The findings in this study reveal a potential biomarker for SCI treatment.

3.
Int J Surg ; 60: 194-203, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30468903

RESUMO

BACKGROUND: The optimal resection extent for middle-third advanced gastric cancer (AGC) still remains controversial. This study aimed to assess the long-term oncologic outcomes of laparoscopy-assisted distal gastrectomy (LADG) versus laparoscopy-assisted total gastrectomy (LATG) for middle-third AGC. METHODS: A retrospective cohort study was conducted using data from 464 patients who underwent LADG or LATG between September 2007 and March 2013. Propensity score matching (PSM) were used for reducing the confounding effects to compare the long-term oncologic outcomes between two groups. Cox regression analysis was performed to clarify the prognostic factors. RESULTS: After PSM was performed, a well-balanced cohort of 376 patients (188 LADG and 188 LATG) was further analyzed. Of interest, the LADG group had a significantly shorter operative time (244.6 ±â€¯28.0 vs. 259.1 ±â€¯30.1, P < 0.0001), less operative blood loss (142.9 ±â€¯50.9 vs. 157.8 ±â€¯54.1, P = 0.006), earlier day of first flatus (2.6 ±â€¯0.8 vs. 2.9 ±â€¯0.9, P = 0.014), fewer number of retrieved lymph nodes (36.5 ±â€¯7.9 vs. 41.4 ±â€¯9.8, P < 0.0001), and shorter postoperative hospital stay (9.7 ±â€¯1.3 vs. 10.7 ±â€¯1.4, P < 0.0001) than the LATG group. However, no significant differences were observed in days of eating liquid diet (P = 0.626) and days of eating soft diet (P = 0.353). The incidence of overall and severe postoperative complications (Clavien-Dindo grade ≥ IIIa) following the LADG group were significantly fewer than the LATG group (overall, 24.5% vs. 34.6%, P = 0.032; severe, 4.8% vs. 11.2%, P = 0.022). In addition, the LADG group had significantly more favorable overall survival (OS) and disease-free survival (DFS) rates than the LATG group (5-year OS rate, 55.6% vs. 41.8%, P = 0.002; 5-year DFS rate, 45.9% vs. 32.8%, P < 0.001). In multivariate analyses, resection extent was not an independent prognostic factor for OS and DFS. CONCLUSIONS: This PSM cohort analysis has indicated LADG with D2 lymphadenectomy appeared to be safe and reasonable option for patients with middle-third AGC in general. LADG could contribute to improved survival.


Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Pontuação de Propensão , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Gastrectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade
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