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Objective This study aimed to assess the likely association of gut microbiome with low anterior resection syndrome (LARS) symptoms. Postoperative stool samples from patients with minor or major LARS after sphincter-preserving surgery (SPS) for rectal cancer were collected and analyzed using 16S ribosomal RNA sequencing method. The symptom patterns of LARS were classified into two groups (PC1LARS, PC2LARS) using principal component analysis. The dichotomized sum of questionnaire items (sub1LARS, sub2LARS) was used to group patients according to the main symptoms. According to microbial diversity, enterotype, and taxa, PC1LARS and sub1LARS were associated with frequency-dominant LARS symptoms and patients, while PC2LARS and sub2LARS were grouped as incontinence-dominant LARS symptoms and patients. Butyricicoccus levels decreased while overall LARS scores increased. The α-diversity richness index Chao1 showed a significantly negative correlation in sub1LARS and a positive correlation in sub2LARS. In sub1LARS, the severe group showed a lower Prevotellaceae enterotype and higher Bacteroidaceae enterotype than the mild group. Subdoligranulum and Flavonifractor showed a negative and a positive correlation with PC1LARS, respectively, while showing a negative relationship with PC2LARS. Lactobacillus and Bifidobacterium were negatively correlated to PC1LARS. Frequency-dominant LARS had decreased diversity of gut microbiome and showed lower levels of lactic acid-producing bacteria.

The reduction pathway of nitrate (NO3−) and nitrite (NO2−) to nitric oxide (NO) contributes to regulating many physiological processes. To examine the rate and extent of dietary nitrate absorption and its reduction to nitrite, we supplemented rat diets with Na15NO3-containing water (1 g/L) and collected plasma, urine and several tissue samples. We found that plasma and urine showed 8.8- and 11.7-fold increases respectively in total nitrate concentrations in 1-day supplementation group compared to control. In tissue samples—gluteus, liver and eyes—we found 1.7-, 2.4- and 4.2-fold increases respectively in 1-day supplementation group. These increases remained similar in 3-day supplementation group. LC–MS/MS analysis showed that the augmented nitrate concentrations were primarily from the exogenously provided 15N-nitrate. Overall nitrite concentrations and percent of 15N-nitrite were also greatly increased in all samples after nitrate supplementation; eye homogenates showed larger increases compared to gluteus and liver. Moreover, genes related to nitrate transport and reduction (Sialin, CLC and XOR) were upregulated after nitrate supplementation for 3 days in muscle (Sialin 2.3-, CLC1 1.3-, CLC3 2.1-, XOR 2.4-fold) and eye (XOR 1.7-fold) homogenates. These results demonstrate that dietary nitrate is quickly absorbed into circulation and tissues, and it can be reduced to nitrite in tissues (and likely to NO) suggesting that nitrate-enriched diets can be an efficient intervention to enhance nitrite and NO bioavailability.

Particulate matter (PM) is the main component of air pollution. Children are vulnerable to PM and acute otitis media (AOM), which is one of the most common diseases in children. However, studies on the relationship between AOM in children and PM are rare and their results are inconsistent. The aim of this study is to investigate the effect of PM on AOM in children on the basis of the Korea National Health Insurance service (NHIS) claims data. NHIS claim data from 2008 to 2015 was used to identify outpatient visits, antibiotic use to treat AOM, and demographic data. This data was combined with the data on PM2.5 (≤ 2.5 μm) and PM10 (≤ 10 μm according to its aerodynamic diameter) level extracted from air pollution data from Korean National Institute of Environmental Research for 16 administrative regions. The children with AOM were divided into three age groups (2.5 of 10 μg/m3, the relative risk of OM increased by 4.5% in children under 2 years of age. The effect of PM2.5 was strongest influence on the day of exposure. The exposure to PM10 was related to the incidence of AOM on the day of exposure and the following seven days in all three age groups. The PM concentrations did not strongly affect either AOM duration or the use of antibiotics to cure AOM. The RR in the each lag day after exposure to PM10 was diverse according to the age groups. Regardless of PM size and children’s age, the PM levels are positively related to the incidence of AOM. Both PM2.5 and PM10 have the most adverse effects on children under 2 years of age and on the day of exposure.

Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (p p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.

Nitric oxide (NO) signaling has been studied in the eye, including in the pathophysiology of some eye diseases. While NO production by nitric oxide synthase (NOS) enzymes in the eye has been characterized, the more recently described pathways of NO generation by nitrate (NO3−) and nitrite (NO2−) ions reduction has received much less attention. To elucidate the potential roles of these pathways, we analyzed nitrate and nitrite levels in components of the eye and lacrimal glands, primarily in porcine samples. Nitrate and nitrite levels were higher in cornea than in other eye parts, while lens contained the least amounts. Lacrimal glands exhibited much higher levels of both ions compared to other organs, such as liver and skeletal muscle, and even to salivary glands which are known to concentrate these ions. Western blotting showed expression of sialin, a known nitrate transporter, in the lacrimal glands and other eye components, and also xanthine oxidoreductase, a nitrate and nitrite reductase, in cornea and sclera. Cornea and sclera homogenates possessed a measurable amount of nitrate reduction activity. These results suggest that nitrate ions are concentrated in the lacrimal glands by sialin and can be secreted into eye components via tears and then reduced to nitrite and NO, thereby being an important source of NO in the eye.

Colorectal cancer (CRC) represents the third most frequently diagnosed malignancy worldwide and is the second most common cause of tumor-associated mortalities in Korea. Due to the disease’s aggressive behavior, the 5-year survival rate for CRC patients remains unpromising. Well-characterized cell lines have been used as a biological model for studying the biology of cancer and developing novel therapeutics. To assist in vitro studies, 18 CRC cell lines (SNU-1566, SNU-1983, SNU-2172, SNU-2297, SNU-2303, SNU-2353B, SNU-2359, SNU-2373B, SNU-2407, SNU-2423, SNU-2431, SNU-2465, SNU-2493, SNU-2536C, SNU-2621B, SNU-NCC-61, SNU-NCC-376, and SNU-NCC-377) derived from Korean patients were established and characterized in the present study. General characteristics of each cell line including doubling time, in vitro morphology, mutational profiles, and protein expressions of CRC-related genes were described. Whole exome sequencing was performed on each cell line to configure mutational profiles. Single nucleotide variation, frame shift, in-frame deletions and insertions, start codon deletion, and splice stop codon mutation of various genes were found and classified based on their pathogenicity reports. In addition, cell viability was assayed to measure their sensitivities to 24 anti-cancer drugs including anti-metabolites, kinase inhibitors, histone deacetylase inhibitors, alkylating inhibitors, and topoisomerase inhibitors, all widely used for various cancers. On testing, five CRC cell lines showed MSI, of which MLH1 or MSH6 gene was mutated. These newly established CRC cell lines can be used to investigate biological characteristics of CRC, particularly for investigating gene alterations associated with CRC.

We aimed to compare the short- and long-term outcomes of simultaneous laparoscopic, hybrid, and open resection for colorectal cancer and synchronous liver metastases. We retrospectively analyzed the data of 647 patients with simultaneous resection of colorectal cancer and liver metastases between January 2006 and December 2018 at three tertiary referral hospitals. Patient’s baseline characteristics, perioperative outcomes, pathological examination results, liver-specific recurrence rate and survivals were compared between the propensity score-matched groups. Forty-two and 81 patients were selected for the laparoscopic vs. hybrid groups, and 48 and 136 patients for laparoscopic vs. open groups, respectively. The laparoscopic group had fewer wound complications (2.1 vs. 13.2%; p = 0.028) than the open group, and a shorter postoperative hospital stay than the hybrid and open groups (8 vs. 11 days, p

To date, the effect of adjuvant chemotherapy after curative resection in patients with stage II colon cancer remains controversial. Still, little is known about the effects of adjuvant chemotherapy in patients with stage II colon cancer who are older than 70 years, as most studies did not focus on this population. This study aimed to investigate the oncologic outcomes of elderly patients with stage II colon cancer who underwent curative resection with or without postoperative adjuvant chemotherapy. We retrospectively reviewed medical records of patients older than 70 years who underwent curative resection of stage II primary colon cancer during 2002–2015. Patients were classified into surgery alone (SA) and adjuvant chemotherapy (AC) groups and propensity score-matched at a 1:1 ratio using a logistic regression. The end points were recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Of the 623 patients who met the criteria, 145 were assigned to each arm after propensity score matching. The mean ages of the SA and AC groups were 74.3 and 74.0 years, respectively. A log-rank test revealed no significant inter-group differences in RFS (p = 0.202), CSS (p = 0.486) or OS (p = 0.299). In a Cox regression analysis, adjuvant chemotherapy was not found to be an independent factor affecting RFS (p = 0.206), CSS (p = 0.487) or OS (p = 0.301). Adjuvant chemotherapy does not appear to yield survival benefits in elderly patients with stage II colon cancer.

If anastomotic site leakage is expected after laparoscopic low anterior resection (LAR), de-functioning ileostomy is required. However, there is controversy about the consequence of stoma formation via the specimen extraction site (SES). Therefore, we aimed to investigate stoma-related complication according to stoma formation via the SES. We enrolled rectal cancer patients who underwent laparoscopic LAR with temporary ileostomy between January 2013 and December 2017. Patients were divided into two groups: stoma through the SES (SES) and stoma through a new site (NS). The difference in the incidence of stoma-related complications was analysed. In total, 198 patients underwent laparoscopic LAR (SES = 141 patients, NS = 57 patients). The SES group had a shorter operation time (204.7 ± 74.4 min vs 229.5 ± 90.5 min, p = 0.049) and was associated with fewer cases of wound infection (0% vs 7%, p = 0.006) than the NS group. There was no statistically significant difference between the SES group and NS group in all-stoma complications (22.7% vs 12.3%, p = 0.095). The incidence of parastomal hernia also was not significantly different (11.3% vs 5.3%, p = 0.286). Stoma via the SES is feasible after laparoscopic LAR with temporary ileostomy, although stoma-related complication rate was higher, without a significant difference. It can shorten the operation time and reduce wound infection rate.

Flag leaves (FL) and second leaves (SL) in rice show differential aging patterns during monocarpic senescence. Coordination of aging programs between FL and SL is important for grain yield and quality. However, the molecular bases for differential aging programs between FL and SL have not been systematically explored in rice. Here, we performed mRNA-sequencing of FL and SL at six time points during grain-filling and identified four molecular bases for differential aging programs between FL and SL: phenylpropanoid biosynthesis, photosynthesis, amino acid (AA) transport, and hormone response. Of them, photosynthesis (carbon assimilation) and AA transport (nitrogen remobilization) predominantly occurred in FL and SL, respectively, during grain-filling. Unlike other molecular bases, AA transport showed consistent differential expression patterns between FL and SL in independent samples. Moreover, long-distance AA transporters showed invariant differential expression patterns between FL and SL after panicle removal, which was consistent to invariant differential nitrogen contents between FL and SL after panicle removal. Therefore, our results suggest that the supplies of carbon and nitrogen to seeds is functionally segregated between FL and SL and that long-distance AA transport is an invariant core program for high nitrogen remobilization in SL.

In-situ TEM investigation of aging response in an Al–7.8 at.% Li was performed at 200 °C up to 13 hours. Semi-spherical δ′ precipitates growing up to an average radius of 7.5 nm were observed. The size and number of individual precipitates were recorded over time and compared to large-scale phase-field simulations without and with a chemo-mechanical coupling effect, that is, concentration dependence of the elastic constants of the matrix solid solution phase. This type of coupling was recently reported in theoretical studies leading to an inverse ripening process where smaller precipitates grew at the expense of larger ones. Considering this chemo-mechanical coupling effect, the temporal evolution of number density, average radius, and size distribution of the precipitates observed in the in-situ experiment were explained. The results indicate that the mechanism of inverse ripening can be active in this case. Formation of dislocations and precipitate-free zones are discussed as possible disturbances to the chemo-mechanical coupling effect and consequent inverse ripening process.

Common genetic risk variants for colorectal cancer (CRC) have been identified at approximately 40 loci by genome-wide association studies (GWAS). We investigated the association of these risk variants by age at onset of CRC using case-only and case-control analysis. A total of 1,962 CRC cases and 2,668 controls from two independent case-control studies conducted by Korea’s National Cancer Center were included in this study. We genotyped 33 GWAS-identified single-nucleotide polymorphisms (SNPs) associated with CRC risk. The risk allele in SNP rs704017, located at 10q22.3 in the ZMIZ1-AS1 gene, was consistently less frequent among CRC patients aged P = 2.7 × 10−3, in an additive model), although this did not surpass the threshold for multiple testing. The direction of associations between rs704017 and CRC risk differed by age group in the combined case-control analysis (P = 0.03 and ≥50 years: OR = 1.13, 95% CI = 0.98–1.29, P = 0.09, in a dominant model); the p-values for heterogeneity (Pheterogeneity = 7.5 × 10−3) and for interaction were statistically significant (Pinteraction = 7.8 × 10−3, in the dominant model). Our results suggest that the CRC susceptibility SNP rs704017 has a hereditary effect on onset age of CRC.