GNA13 has been found overexpressed in various types of cancer, which is related to tumor metastasis and progression. However, the biological functions of GNA13 in colorectal cancer (CRC) progression remain unclear. This study aimed to explore the role of GNA13 in CRC and investigate the mechanism of how GNA13 promotes tumor growth. Interestingly, our findings showed that GNA13 is commonly upregulated in CRC, where these events are associated with a worse histologic grade and poor survival. Increased expression levels of GNA13 promoted cell growth, migration, invasion, and epithelial‐mesenchymal transition, whereas GNA13 silencing abrogated these malignant phenotypes. In addition, overexpressing GNA13 in cancer cells increased the levels of the chemokines CXCL1, CXCL2, and CXCL4, which contributed to CRC proliferation and colony formation. Moreover, our mechanistic investigations suggest that the NF‐κB/p65 signaling pathway was activated by the increase in GNA13 levels. Inhibiting the NF‐κB/p65 pathway with an inhibitor decreased GNA13‐induced migration, invasion and CXCL chemokine level increases, indicating the critical role of NF‐κB/p65 signaling in mediating the effects of GNA13 in CRC. Together, these results demonstrate a key role of GNA13 overexpression in CRC that contributes to malignant behavior in cancer cells, at least in part through stimulating angiogenesis and increasing the levels of the NF‐κB‐dependent chemokines CXCL1, CXCL2, and CXCL4.
Evidences accumulated that the death of neutrophils are not the end of their missions. The neutrophil extracellular traps (NETs), web-like structure, formed after neutrophils dying contribute greatly to immune defense, in both innate and adaptive immunity. Interestingly, previous studies revealed that the generation and activation of NETs do not only rely on bacteria induction, but also in patients with sterile inflammatory diseases, implying an undeniable correlation between NETs and these diseases. This review summarized the latest findings that the crucial roles of NETs in sterile inflammatory diseases, as well as novel targeted therapy based on these new discoveries.
BackgroundSitus inversus totalis (SIT) refers to an unusual condition involving reversal of abdominal and thoracic viscera, with an incidence rate of 1/5000–20,000 adults. Minimally invasive surgeries for SIT patients are technically challenging, while the surgical experience for SIT patients is quite limited.Case presentationA 61-year-old man, previously diagnosed as SIT, came to our hospital for 6 months history of hematochezia and altered bowel habit. A diagnosis of rectal cancer was made in view of colonoscopic biopsy which confirmed an irregular circumferential lump of well differentiated adenocarcinoma at 10 cm from the anal verge. The computed tomography contrast-enhanced (thorax + abdomen + pelvis) scan revealed a total transposition of abdominal and thoracic organs and an enhanced eccentric mass of rectal but with no evidence of distant metastasis. Robotic low anterior resection (LAR) plus transanal natural orifice specimen extraction (NOSE) was performed after obtaining informed consent. The procedure was performed successfully and the patient convalesced nicely without any complications. The postoperative pathological diagnosis revealed a 4x4x0.6 cm3 moderately differentiated adenocarcinoma and circumferential clearance.ConclusionsRobotic LAR plus transanal NOSE for rectal cancer patients with SIT can be performed safely and may be an effective approach in contrast to open or laparoscopic approach, despite the unconventional anatomy.
A ratiometric fluorescent probe was described for imaging the production of peroxynitrite in cells stimulated by 5-FU.
Rationale: Ankylosing spondylitis (AS) and Kimura's disease (KD) which is quite rare are both chronic inflammatory diseases. Recently we encountered a patient who suffered from KD and AS, and some of his family members also suffer from AS. We, therefore, investigated this unique case and conducted the family-based whole exome sequencing to explore the possible genetic alterations. Patient concerns: Here, we reported a case of a 44-year-old Chinese man with multiple painless masses all over his body and a back pain for 32 years. His uncle and sister were diagnosed with AS. Diagnosis: The diagnosis of KD was based on the patient's clinical features and the biopsy of the neck masses. The diagnosis of AS was based on the patient's clinical features, HLA-B27(+) and the radiologic changes of sacroiliac joints. The genetic test showed that ARPC1B gene which was associated with recurrent infections, auto-inflammatory changes and elevated IgE levels was mutated in this patient. Interventions: Neck masses were removed by surgery. Systemic glucocorticoid, nonsteroidal anti-inflammatory agents, combined with cyclosporine were orally administered, and Etanercept was injected subcutaneously. Outcomes: The masses disappeared rapidly after surgery combined with systemic glucocorticoid, but relapsed shortly after the therapy was discontinued. Low dose glucocorticoid, cyclosporine and Etanercept could keep both KD and AS remained long-term remission. Lessons: Our experience suggests that low dose glucocorticoid, cyclosporine and Etanercept could be beneficial for the patient with KD and AS. The mutation of ARPC1B gene in this case, which is associated with immunologic disturbance, may increase the susceptibility of KD.
Background: Insulin resistance (IR) is closely associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, remission of insulin sensitivity after bariatric surgery in patients with T2DM and a body mass index (BMI) of 27.5–32.5 kg/m2 has not been fully elucidated.Methods: Thirty-six T2DM patients with a BMI of 27.5–32.5 kg/m2 were prospectively consecutively recruited for laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). Hyperinsulinemic euglycemic clamp, oral glucose tolerance test (OGTT), and other indicators were tested at baseline and 6 months postoperative. Glucose disposal rate (GDR), time to reach euglycemia, homeostatic model assessment of IR, quantitative insulin sensitivity check index (QUICKI), triglyceride glucose (TyG) index, 30-min insulinogenic index (IGI30), and disposition index (DI) were calculated at baseline and 6 months after surgery. The criterion for remission in T2DM patients was the achievement of the triple composite endpoint.Results: Anthropometric and glucolipid metabolism parameters significantly improved following surgery. The GDR increased significantly from baseline to 6 months after LRYGB (from 4.28 ± 1.70 mg/kg/min to 8.47 ± 1.89 mg/kg/min, p < 0.0001) and LSG (from 3.18 ± 1.36 mg/kg/min to 7.09 ± 1.69 mg/kg/min, p < 0.001). The TyG index decreased after surgery (RYGB group, from 9.93 ± 1.03 to 8.60 ± 0.43, p < 0.0001; LSG group, from 10.04 ± 0.79 to 8.72 ± 0.65, p = 0.0002). There was a significant reduction in the IGI30 (RYGB group, from 2.04 ± 2.12 to 0.83 ± 0.47, p = 0.005; LSG group, from 2.12 ± 1.73 to 0.92 ± 0.66, p = 0.001). The mean DI significantly increased from 1.14 ± 1.35 to 7.11 ± 4.93 in the RYGB group (p = 0.0001) and from 1.25 ± 1.78 to 5.60 ± 4.58 in the LSG group (p = 0.003). Compared with baseline, HOMR-IR, QUICKI, area under the curve-C-peptide release test (AUC-CRT), and AUC-OGTT were significantly changed at 6 months postoperative. Overall, 52.63% of patients in the LRYGB group versus 29.41% of patients in the LSG group achieved the triple composite endpoint.Conclusion: Both LRYGB and LSG effectively induced remission of IR in patients with T2DM and a BMI of 27.5–32.5 kg/m2.
To explore the safety and feasibility of totally robotic distal gastrectomy (TRDG) for gastric cancer patients who undergo distal gastrectomy. Methods: Consecutive patients with gastric cancer who underwent TRDG (TRDG group) and robotic-assisted distal gastrectomy (RADG) (RADG group) were systematically reviewed at the Second Xiangya Hospital of Central South University from October 2015 to August 2018. Data were collected and statistically analyzed. Results: A total of 161 consecutive patients were included in this study: 84 cases in the TRDG group and 77 in the RADG group. Clinical characteristics and pathological results were mostly similar in both groups. The TRDG group had a significantly longer anastomotic time (20.6 ± 3.3 vs. 17.5 ± 4.0 min, p ˂ 0.001) but showed no difference in total operating time (167.0 ± 18.0 vs. 162.9 ± 17.6 min, p = 0.159). The postoperative hospitalization in the TRDG group was shorter than that in the RADG group (6.7 ± 1.2 vs. 7.2 ± 1.7 days, p = 0.019). Conversion rate, estimated blood loss, and postoperative complications were similar in both groups. There were no statistical differences in the estimated 2-year disease-free survival and overall survival rate between both groups. Conclusions: Although our current results need to be verified in further studies, TRDG represents a safe and feasible approach to distal gastrectomy and embodies the theory of minimally invasive surgery.
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