To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography.

BACKGROUND: Over 90% of rectal cancer patients develop low anterior resection syndrome (LARS) after sphincter-preserving resection. The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong, which hinders the research and treatment of LARS. AIM: To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging (MRI) defecography, and pathogenesis of LARS. METHODS: We evaluated 34 patients using the standard LARS score, and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score. RESULTS: In the LARS score model, there were 10 (29.41%) mild and 24 (70.58%) severe cases of LARS. The comparison of defecation rate between the two groups was 29.36 ± 14.17% versus 46.83 ± 18.62% (P = 0.004); and MRI-rectal compliance (MRI-RC) score was 3.63 ± 1.96 versus 7.0 ± 3.21 (P = 0.001). Severe and mild LARS had significant differences using the two evaluation methods. There was a significant negative correlation between LARS and MRI-RC score (P < 0.001), and they had a negative correlation with defecation rate (P = 0.028). CONCLUSION: MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

MicroRNA-766-3p-mediated downregulation of HNF4G inhibits proliferation in colorectal cancer cells through the PI3K/AKT pathway.

Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC.

Multiple organ dysfunction due to a rare complication of Nuss procedure for pectus excavatum: A case report.

A 19-year-old male patient who suffered from sudden and repeated multiple organ dysfunction syndrome one month after the bar removal procedure of Nuss surgery for pectus excavatum was admitted to our department. With organ function supportive treatment, the etiology was finally identified to be a bone spur located at the inner border of the left costa due to repeated friction between the implanted steel bar and the rib, which damaged the heart repeatedly and induced the consequent acute cardiac tamponade. After operation, the patient was successfully managed and discharged. Follow-ups till three years indicated a good recovery.

Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses.

BACKGROUND: Amlexanox (ALX), a TBK1 inhibitor, can modulate immune responses and has anti-inflammatory properties. To investigate its role in regulating the progression of experimental autoimmune encephalomyelitis (EAE), we studied the effect of ALX on the maturation of dendritic cells (DCs) and the responses of effector and regulatory T cells (Tregs). METHODS: In vitro, bone marrow-derived DCs (BMDCs) were cultured and treated with ALX. Their proliferation, maturation, and their stimulatory function to induce T cells responses were detected. In vivo, the development of EAE from different groups was recorded. At the peak stage of disease, HE, LFB, and electronic microscope (EM) were used to evaluate inflammation and demyelination. Maturation of splenic DC and Th1/Th17/Treg response in the CNS and peripheral were also detected. To further explore the mechanism underlying the action of ALX in DC maturation, the activation of TBK1, IRF3, and AKT was analyzed. RESULTS: Our data indicated that ALX significantly inhibited the proliferation and maturation of BMDCs, characterized by the reduced MHCII, a co-stimulatory molecule, IL12, and IL-23 expression, along with morphological alterations. Co-culture of ALX-treated BMDCs inhibited allogeneic T cell proliferation and MOG-specific T cell response. In EAE mice, ALX significantly attenuated the EAE development by decreasing inflammatory infiltration and demyelination in the spinal cords, accompanied by reduced frequency of splenic pathogenic Th1 and Th17 cells and increased Tregs. Moreover, ALX treatment decreased Th1 and Th17 cytokines, but increased Treg cytokines in the CNS and spleen. Notably, ALX treatment reduced the frequency and expression of CD80 and CD86 on splenic DCs and lowered IL-12 and IL-23 secretion, further supporting an impaired maturation of splenic DCs. In addition, ALX potently reduced the phosphorylation of IRF3 and AKT in BMDC and splenic DCs, both of which are substrates of TBK1 and associated with DC maturation. CONCLUSIONS: ALX, a TBK1 inhibitor, mitigated EAE development by inhibiting DC maturation and subsequent pathogenic Th1 and Th17 responses while increasing Treg responses through attenuating the TBK1/AKT and TBK1/IRF3 signaling.

Perianal Infections in the Phase before Engraftment after Allogeneic Hematopoietic Stem Cell Transplantations: A Study of the Incidence, Risk Factors, and Clinical Outcomes.

In this study, we aimed to investigate the incidence, risk factors, and clinical outcomes of perianal infections during the pre-engraftment phase after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Consecutive patients who underwent non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology from January 1 to December 31, 2016 were enrolled (n = 646). Ninety-nine patients were found to have perianal infections during the pre-engraftment phase, and 80 were found to have neutropenia on perianal infection diagnosis. The cumulative incidence of perianal infection during the pre-engraftment phase after allo-HSCT was 15.3%. A history of perianal infection (hazard ratio [HR] = 15.28, p < 0.001) or hemorrhoids before allo-HSCT (HR = 3.09, p = 0.001) was significantly associated with the new occurrence of perianal infection after allo-HSCT. All patients received empirical broad-spectrum antimicrobial therapies, and 97 were cured after treatment. The clinical outcomes at 100 days after allo-HSCT were comparable in patients with and without perianal infections. In summary, patients who had perianal infection or hemorrhoids before allo-HSCT had a higher risk of new occurrence of perianal infection after allo-HSCT. With appropriate treatment, perianal infection during the pre-engraftment phase did not influence the clinical outcomes.

Expressions of connexin 32 and 26 and their correlation to prognosis of non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: Gap junction intercellular communication (GJIC) plays an important role in regulating homeostasis and differentiation in many tissues. Connexins are gap junction proteins, whose expressions directly affect the function of GJIC. This study was to investigate expressions of connexin 32 and 26 proteins in non-small cell lung cancer (NSCLC), and their correlation to clinicopathological characters of NSCLC. METHODS: Immunohistochemistry was applied to detect expressions of connexin 32 and 26 in 77 NSCLC tissues. Correlations of connexin 32 and 26 expressions to smoking, tumor size, histological type, the degree of differentiation, lymph node metastasis and prognosis were analyzed. RESULTS: The positive rates of connexin 32 and 26 were 51.9% and 40.3% in the 77 samples, which were significantly higher than 20.3% and 30.5% in alveolar epithelium (p = 0.000, r = -0.322; p = 0.013, r = -0.215). Positive expression of connexion 32 was positively correlated with the differentiation degree of NSCLC tissues (p = 0.010, r = 0.345). The one- to five-year survival rates were higher in patients with positive connexion 32 expression than those without (p = 0.005). Moreover, the positive rate of connexin 26 was not correlated to smoking, tumor size, histological type, the degree of differentiation, lymph node metastasis and the postoperative survival time (p > 0.05). CONCLUSIONS: Expression of connexin 32 is closely correlated to the differentiation of NSCLC and affects the prognosis of NSCLC patients. Increasing the expression of connexin 32 may improve the prognosis of NSCLC.

[Expression and significance of CD44(+)ESA(+)CD24(-/low), stem cell markers for breast cancer, in non-small-cell lung carcinoma].

BACKGROUND & OBJECTIVE: Stem cells are found in all human tissues, while tumor stem cells (TSCs) are also detected in tumors. TSC of breast cancer has been separated and its markers have been affirmed. However, TSC of lung carcinoma has not been separated yet. This study was to investigate the expression and significance of stem cell markers for breast cancer (CD44(+)ESA(+)CD24(-/low)) in non-small-cell lung carcinoma (NSCLC). METHODS: Expressions of CD44,ESA and CD24 of tumor tissues in 77 cases of NSCLC patients were detected using immunohistochemistry. The correlations of the expression of the makers to tumor size, smoking, histological type, differentiation, lymphoid metastasis, and prognosis were analyzed. RESULTS: The expressive rates of CD44,ESA and CD24 were 63.6%, 66.2% and 7.8%, respectively in 77 NSCLC tissues. CD44-positive expression was significantly higher in poorly differentiated and undifferentiated group than in well differentiated group. ESA-positive expression was significantly higher in well differentiated group than in poorly differentiated and undifferentiated group. The ESA positivity was significantly higher in glandular carcinoma than in squamous carcinoma. The expressive rate of CD44(+)ESA(+)CD24(-/low) in 77 cases of NSCLC was 36.4%. No correlations were found in the expression of CD44(+)ESA(+)CD24(-/low) to smoking, tumor size, histological type, differentiation, lymphoid metastasis and prognosis (P>0.05). CONCLUSION: Expressions of stem cell markers for breast cancer (CD44(+)ESA(+)CD24(-/low)) are not associated with tumor size, histological type, differentiation, lymphoid metastasis and prognosis of NSCLC.