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We describe a Chinese family with severe autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) and psychiatric problems in whom whole-exome family trio sequencing identified a heterozygous mutation in the potassium channel subfamily T, member 1 (KCNT1), a sodium-gated potassium channel gene, which was a novel missense mutation c.2153A>T (p. Asp718Val). The typical characteristics of the three patients in the family were refractory epilepsy, acquired cognitive impairment, and psychiatric problems, which include hallucinations and suicidal thoughts and behaviors. The age at onset was found to be earlier in son and daughter of the proband than that of the proband, as proven by the proband’s history of an epileptic seizure at the age of 16 years and her son’s and daughter’s history of seizures at the age of 8 years. Magnetic resonance imaging findings were negative for any abnormalities. Because of psychiatric symptoms, these three patients were administered risperidone at different times during their illness. The protestor’s son had tried fenofibrate treatment, but clinical remission was unclear. In summary, our findings broadened the mutation database in relation to KCNT1 and implicated the sodium-gated potassium channel complex in ADNFLE, more broadly, in the pathogenesis of focal epilepsies.

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/β‐catenin pathway, but it is highly expressed in colon cancer and can promote colon cancer cell proliferation. miRNAs are involved in the occurrence and progression of many tumors. However, miRNAs that can regulate NKD1 and the mechanisms by which NKD1 regulates tumor progression remain ambiguous. This research aims to reveal the potential regulatory network of NKD1 in colon cancer. miRNA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed by bioinformatics to screen for potential miRNAs targeting NKD1. Let‐7b‐5p was found to inhibit proliferation, migration, and invasion of colon cancer cells targeting NKD1. Further studies suggested that let‐7b‐5p can modulate Wnt signaling activity, and the nuclear accumulation of β‐catenin was significantly restrained by let‐7b‐5p through targeting NKD1. Moreover, NKD1 could prohibit the expression of the APC protein. Further studies manifested that NKD1 bound to APC and promoted the ubiquitination degradation of APC through restraining the expression of the deubiquitinating enzyme USP15 and blocking the combination between USP15 and APC. Functionally, NKD1 enhanced the proliferation and migration of colon cancer cells by inhibiting APC expression. This research revealed a novel mechanism by which the let‐7b‐5p‐NKD1‐APC‐β‐catenin signaling pathway inhibited colon cancer cell progression. [ABSTRACT FROM AUTHOR]

Background: Drug resistance is an important factor affecting the efficacy of chemotherapy in patients with colon cancer. However, clinical markers for diagnosing drug resistance of tumor cells are not only a few in number, but also low in specificity, and the mechanism of action of tumor cell drug resistance remains unclear. Methods: Dipeptidase 1 (DPEP1) expression was analyzed using the cancer genome atlas (TCGA) and genotype‐Tissue Expression pan‐cancer data. Survival analysis was performed using the survival package in R software to assess the prognostic value of DPEP1 expression in colon cancer. Correlation and Venn analyses were adopted to identify key genes. Immunohistochemistry, western blot, qRT–PCR, Co‐immunoprecipitation, and dual‐luciferase reporter experiments were carried out to explore the underlying associations between DPEP1 and Achaete scute‐like 2 (ASCL2). MTT assays were used to evaluate the role of DPEP1 and ASCL2 in colon cancer drug resistance. Results: DPEP1 was highly expressed in colon cancer tissues. DPEP1 expression correlated negatively with disease‐specific survival but not with overall survival. Bioinformatics analysis and experiments showed that the expressions of DPEP1 and ASCL2 in colon cancer tissues were markedly positively correlated. Mechanistic research indicated that DPEP1 enhanced the stability of protein ASCL2 by inhibiting its ubiquitination‐mediated degradation. In turn, ASCL2 functioned as a transcription factor to activate the transcriptional activity of the DPEP1 gene and boost its expression. Furthermore, DPEP1 also could enhance the expression of colon cancer stem cell markers (LGR5, CD133, and CD44), which strengthened the tolerance of colon cancer cells to chemotherapy drugs. Conclusions: Our findings reveal that the DPEP1 enhances the stemness of tumor cells by forming a positive feedback loop with ASCL2 to improve resistance to chemotherapy drugs. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are a type of regulatory molecule with potential roles in the development of several different malignancies. However, the underlying mechanisms of lncRNAs in colorectal cancer (CRC) are incompletely understood. The present study investigated the molecular mechanism of LINC02038 in CRC. LINC02038 expression was decreased in CRC tissues compared to the para‑cancerous tissues and LINC02038 overexpression markedly reduced the proliferation, vitality, migration and invasive ability and greatly accelerated apoptosis of colorectal cancer cells. Bioinformatics examination indicated that LINC02038 may have targeted microRNA (miR)‑552‑5p. RNA immunoprecipitation and luciferase reporter assays showed that LINC02038 served as a sponge for miR‑552‑5p, hindering target gene FAM172A of miR‑552‑5p degradation. Moreover, methylated RNA immunoprecipitation (MeRIP)‑qualitative PCR assays revealed that YTHDF2 could identify and regulate the METTL3‑mediated LINC02038 N6‑methyladenosine (m 6 A) modification and increase its degradation, thereby promoting CRC progression via the PI3K/AKT pathway. Based on the CRC clinical specimens, it was shown that LINC02038 was negatively associated with lymphatic metastasis and distant metastasis. These results revealed that m 6 A/LINC02038/miR‑552‑5p/FAM172A may be a novel anti‑tumor axis and LINC02038 may serve as a biomarker and treatment option for colorectal cancer.

Objective To detect the frequencies of myeloid-derived suppressor cells (MDSCs) in the peripheral blood of patients with colorectal cancer (CRC) in an attempt to investigate the relationship between the change of MDSC frequencies and clinicopathologic characteristics of CRC patients. Methods The frequencies of granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs) in the peripheral blood of 82 CRC patients and 30 healthy volunteers were detected by flow cytometry. ANOVA and t-test were used to explore the relationship between the frequencies of MDSCs in the peripheral blood and the TNM stages, lymph node metastasis, tumor sites, histological grade as well as common therapeutic measures of CRC patients. Correlation analysis was performed to evaluate the correlation between the frequencies of G-MDSCs and M-MDSCs. Results Compared with the 30 healthy volunteers, the frequencies of G-MDSCs and M-MDSCs in the peripheral blood of the 82 CRC patients were statistically higher. The frequencies of G-MDSCs and M-MDSCs in the peripheral blood from TNF stage III and IV CRC patients were obviously higher than those from stage I and II patients, and CRC patients with lymph node metastasis had remarkably higher frequencies of G-MDSCs and M-MDSCs than the patients without lymph node metastasis. There were no statistical differences in the frequencies of G-MDSCs and M-MDSCs in the peripheral blood between CRC patients with different tumor sites as well as histological grades. Radical resection and effective adjuvant chemotherapy significantly decreased the frequencies of G-MDSCs and M-MDSCs in the peripheral blood of CRC patients. No statistical correlation was found between the frequencies of circulating G-MDSCs and M-MDSCs in CRC patients. Conclusion G-MDSC and M-MDSC frequencies in the peripheral blood of CRC patients significantly increased, and were closely associated with TNM stages and lymph node metastasis. Radical resection and effective adjuvant chemotherapy significantly reduced the frequencies of circulating G-MDSCs sand M-MDSCs of CRC patients.

Objective: To study postoperative anorectal dynamic change in ultra-low rectal cancer patients undergoing laparoscopic intersphincteric resection., Methods: Clinical and follow-up data of 26 ultra-low rectal cancer patients undergoing laparoscopic intersphincteric resection in our department from January 2007 to January 2013 were retrospectively analyzed (observation group). Thirty rectal cancer patients undergoing laparoscopic low anterior resection by the same surgical team in the same period from the Medical Record Room were randomly extracted as control group. The observation indexes included preoperative and postoperative anal resting pressure(ARP), anal maximum squeeze pressure (AMSP), rectal maximum tolerable volume (RMTV), rectal anal inhibition reflex (RAIR) and Wexner anal function scores (0 means normal)., Results: There were no significant differences in clinical baseline data between the two groups(all P>0.05), except the distance from lower edge of tumor to dentate line [(2.9±0.4) cm in observation group vs. (5.0±0.5) cm in control group, P=0.000]. There were no differences in preoperative anorectal manometry and Wexner anal function score between two groups (all P>0.05). The average follow-up time in observation group and control group was 14.5 months and 14.0 months respectively. Three months after operation, significant differences between observation group and control group (all P=0.000) were as follows: defecation frequency [(6.0±1.5) times/day vs. (2.5±1.0) times/day], Wexner anal function score(5.0±0.9 vs. 2.9±1.2), ARP [(32.0±6.7) mmHg vs. (45.0±8.2) mmHg], AMSP [(90.1±6.9) mmHg vs. (110.0±7.5) mmHg], RMTV [(61.0±7.2) ml vs. (91.1±7.5) ml] and positive rate of RAIR [11.5%(3/26) vs. 66.7%(20/30)]. One year after surgery, there were no significant differences in defecation frequency, Wexner anal function scores, ARP, AMSP and RMTV between the two groups (all P>0.05), however the difference in positive rate of RAIR was still significant[38.5%(10/26) vs. 93.3%(28/30), P=0.000]., Conclusion: Laparoscopic intersphincteric resection for ultra- low rectal cancer can achieve satisfactory anorectal dynamic effect.