Inactivation of p16 by methylation of CpG islands is a frequent early event in gastric carcinogenesis. The positive relationship between p16 methylation and the clinical characteristics of gastric carcinomas (GC) has not been reported to date. In the present study, a DHPLC assay to quantify p16 methylation was established (detection limit by fluorescence detector: 1:255 (Methlyated vs Unmethylated)). The proportion of methylated p16 in the representative samples was confirmed and standardized by clone sequencing. Then, the DHPLC and two regular methylation-specific PCR (MSP) assays were used to detect p16 methylation in 82 paired, resected GCs and their adjacent normal tissues. Results showed that the average proportion of methylated p16 in GCs was significantly higher than that in their adjacent samples (12.90 vs 0.63%; t-test P ¼ 0.005). A much higher proportion of methylated p16 was detected in GCs with metastases (local or distant) than without metastases (14.76 vs 2.61%; t-test P ¼ 0.014). A proportional relationship was observed between clinical stages and positive rates of p16 methylation in GCs and/or adjacent tissues: 27.3, 37.5, and 58.8% (by DHPLC) for stage-I, -II, -III-IV of GCs, respectively (two-sided Fisher's exact test P ¼ 0.016). To confirm the data obtained by DHPLC, two MSP primer sets (p16-M and p16-M2) were also used to analyze p16 methylation in the same set of samples simultaneously. Data of MSP assay using the primer set p16-M2, but not p16-M, correlated with that of DHPLC. These results imply that the primer set p16-M2 might be more suitable than p16-M to detect p16 methylation in gastric tissues. In conclusion, the present data indicates that p16 methylation correlates with progression of GCs significantly.

Background: Currently, there are few studies on the characteristics of lymph node metastasis in the central region in patients with preoperative negative lymph node (cN0) papillary thyroid carcinoma (PTC) coexistent with Hashimoto's thyroiditis (HT). There is still a significant controversy on whether to perform prophylactic central compartment lymph node dissection for T1/T2 cN0 PTC. Therefore, we aimed to investigate the characteristics and risk factors of central compartment lymph node metastasis in cN0 PTC (T1 or T2 stage) coexists with HT. Methods: From Jun. 2015 to Apr. 2019, the clinicopathological data of 354 patients with stage T1/ T2 cN0 PTC admitted to the thyroid tumor surgery of Inner Mongolia People's Hospital were analyzed retrospectively. All patients underwent central compartment lymph node dissection. According to the results of the postoperative pathological examination, the patients were divided into two groups: PTC group (n=236) and PTC coexistent with the HT group (n=118).Results: The proportion of PTC patients with HT was 33.33% (118/354) in T1/T2 cN0 PTC patients; most of them were women. The levels of serum thyrotropin, antithyroglobulin antibody, and thyroid peroxidase antibody in PTC coexistent with HT group are higher than those in the PTC group (P<0.05).The number of lymphadenectomies in PTC coexistent with HT group was more than that in PTC alone group (P<0.05). Univariate analysis showed that antithyroglobulin antibody positive, tumor diameter >1 cm, and multifocal cancer in T1/T2 stage cN0 PTC coexistent with HT group were all correlated with lymph node metastasis in the central region (P<0.05). Logistic regression analysis showed that tumor diameter >1 cm, and multifocal cancer were the risk factors of central compartment lymph node metastasis in patients with T1/T2 stage cN0 PTC coexistent with HT (P<0.05).Conclusions: HT is not a relevant factor of central lymph node metastasis in T1/T2 cN0 PTC; regardless of the presence or absence of HT, tumor diameter >1 cm and multifocal cancer are risk factors for central lymph node metastasis in patients with T1/T2 cN0 PTC. Therefore, preventive lymph node dissection in the central region should be conducted actively during the operation.

<b><i>Introduction:</i></b> The cohort study aimed to assess the association of nighttime sleep duration and the change in nighttime sleep duration with chronic kidney disease (CKD) and whether the association between nighttime sleep duration and CKD differed by daytime napping. <b><i>Methods:</i></b> This study included 11,677 individuals from the China Health and Retirement Longitudinal Study (CHARLS) and used data from the 2011 baseline survey and four follow-up waves. Nighttime sleep duration was divided into three groups: short (&lt;7 h per night), optimal (7–9 h), and long nighttime sleep duration (&gt;9 h). Daytime napping was divided into two groups: no nap and with a nap. We used Cox proportional hazards model to examine the effect of nighttime sleep duration at baseline and change in nighttime sleep duration on incident CKD and a joint effect of nighttime sleep duration and nap time on onset CKD. <b><i>Results:</i></b> With a follow-up of 7 years, the incidence of CKD among those with short, optimal, and long nighttime sleep duration was 9.89, 6.75, and 9.05 per 1,000 person-years, respectively. Compared to individuals with optimal nighttime sleep duration, short nighttime sleepers had a 44% higher risk of onset CKD (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.21–1.72). Compared to participants with persistent optimal nighttime sleep duration, those with persistent short or long nighttime sleep duration had an increased risk of incident CKD (HR: 1.44, 95% CI: 1.15–1.80). We found a lower incidence of CKD in participants with short nighttime sleep duration and a nap (HR: 0.74, 95% CI: 0.60–0.93), compared to those with short nighttime sleep duration and no nap. <b><i>Conclusion:</i></b> Short nighttime sleep duration and persistent long or short nighttime sleep duration were associated with a higher risk of onset CKD. Keeping persistent optimal nighttime sleep duration may help reduce CKD risk later in life. Daytime napping may be protective against CKD incidence.

ImportanceGrowing evidence indicates that adverse prenatal or intrauterine environments might contribute to the development of high refractive error (RE) later in life. However, the association of maternal hypertensive disorder of pregnancy (HDP) with high RE in offspring during childhood and adolescence remains unknown.ObjectiveTo investigate the association between maternal HDP and overall and type-specific high REs in offspring in childhood and adolescence.Design, Setting, and ParticipantsThis nationwide population-based cohort study included live-born individuals born in Denmark from 1978 to 2018 in the Danish national health registers. Follow-up started at the date of birth and ended at the date of RE diagnosis, 18th birthday, death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 12, 2021, through June 30, 2022.ExposuresMaternal HDP (n = 104 952), including preeclampsia or eclampsia (n = 70 465) and hypertension (n = 34 487).Main Outcomes and MeasuresThe main outcomes were the first occurrence of high RE (hyperopia, myopia, and astigmatism) in offspring. A Cox proportional hazards regression model was used to examine the association between maternal HDP and risk of high RE in offspring from birth until age 18 years, adjusting for multiple potential confounders.ResultsThis study included 2 537 421 live-born individuals, 51.30% of whom were male. During the follow-up of up to 18 years, 946 offspring of 104 952 mothers with HDP (0.90%) and 15 559 offspring of 2 432 469 mothers without HDP (0.64%) were diagnosed with high RE. The cumulative incidence of high RE was higher in the exposed cohort (1.12%; 95% CI, 1.05%-1.19%) than in the unexposed cohort (0.80%; 95% CI, 0.78%-0.81%) at 18 years of age (difference: 0.32%; 95% CI, 0.25%-0.40%). Offspring born to mothers with HDP had a 39% increased risk of overall high RE (hazard ratio [HR], 1.39; 95% CI, 1.31-1.49). Sibling-matched analysis revealed an increased risk of overall high RE in half siblings (HR, 1.21; 95% CI, 1.05-1.39) and full siblings (HR, 1.15; 95% CI, 0.99-1.34), but the difference was not significant for the latter. The elevated risks were observed for hypermetropia (HR, 1.41; 95% CI, 1.30-1.52), myopia (HR, 1.30; 95% CI, 1.10-1.53), and astigmatism (HR, 1.45; 95% CI, 1.22-1.71). The increased risk of high RE persisted among offspring aged 0 to 6 years (HR, 1.51, 95% CI, 1.38-1.65), 7 to 12 years (HR, 1.28; 95% CI, 1.11-1.47), and 13 to 18 years (HR, 1.16; 95% CI, 0.95-1.41), but the difference was not significant for the oldest group. When considering both timing of diagnosis and severity of maternal preeclampsia, the highest risk was observed in offspring prenatally exposed to early-onset and severe preeclampsia (HR, 2.59; 95% CI, 2.17-3.08).Conclusions and RelevanceIn this cohort study of the Danish population, maternal HDP, especially early-onset and severe preeclampsia, was associated with an increased risk of high RE in offspring during childhood and adolescence. These findings suggest that early and regular RE screening should be recommended for children of mothers with HDP.

Objectives: We tended to explore the association of indoor air pollution (IAP) and non-neoplastic digestive system diseases (NNDSD) among the Chinese middle-aged and older population.Methods: From 2011 to 2018, we included 7884 NNDSD-free adults from the China Health and Retirement Longitudinal Study (CHARLS). Physician-diagnosed NNDSD was obtained by self-reported information at baseline and updated across follow-up surveys. We investigated the associations between baseline exposure of solid fuel use for cooking and/or heating and NNDSD diagnosed during follow-up through Cox proportional hazard models. Furthermore, we examined the relationship between cooking fuel switching and NNDSD diagnosed during follow-up.Results: Solid fuel use for cooking and/or heating was positively associated with NNDSD after adjusting for potential confounders. The risk of NNDSD among subjects who always use solid fuel for cooking (adjusted hazard ratio [aHR]: 1.42; 95% confidence interval [CI]: 1.09, 1.84) was higher than those with always clean fuels. Moreover, we found a lower NNDSD risk among participants who switched from solid to clean cooking fuel (aHR: 0.65; 95% CI: 0.49, 0.87) than those with always solid fuels.Conclusion: Our present study shows that indoor solid fuel use is a dependent risk factor for NNDSD. Moreover, switching to clean fuel may contribute to the prevention of digestive system illnesses.