Acid-Promoted Cyclization of α-Azidobenzyl Ketones through C═N Bond Formation: Synthesis of 6-Substituted Quinoline Derivatives.

An acid-promoted cyclization of α-azidobenzyl ketones has been developed for the synthesis of 6-substituted quinoline derivatives. A variety of synthetically useful 6-OTf or -OMs quinoline derivatives were obtained in moderate to good yields. The reaction proceeds via C═N bond formation without organophosphine, providing convenient access to structurally interesting and synthetically important 6-substituted quinoline derivatives in moderate to good yields. A mechanistic perspective that is different from the traditional intramolecular Schmidt reaction has been proposed.

Genome-wide polygenic risk score, cardiometabolic risk factors, and type 2 diabetes mellitus in the Chinese population.

OBJECTIVE: Type 2 diabetes (T2D) is caused by both genetic and cardiometabolic risk factors. However, the magnitude of the genetic predisposition of T2D in the Chinese population remains largely unknown. METHODS: This study included 93,488 participants from the China Kadoorie Biobank, and multiple polygenic risk scores (PRS) were calculated. A common cardiometabolic risk score (CRS) using smoking, alcohol consumption, physical activity, diet, obesity, blood pressure, and blood lipids was constructed to investigate the effects of cardiometabolic risk factors on T2D. Furthermore, an equation based on ideal PRS, CRS, and their interaction was established to explore the combined effects on T2D. RESULTS: An ideally fitting PRS model (variance explained, R2 = 7.6%) was reached based on multiple PRS calculation methods. An additive interaction between PRS and CRS (coefficient = 28%, 95% CI: 0.20-0.36, p < 0.001) was found. The R2 of the T2D predictive model could increase to 8.3% when CRS and the interaction terms of PRS × CRS were considered. In the etiological composition of T2D, the ratio of genetic risk effect, cardiometabolic risk effect, and interaction between genetic and cardiometabolic factors was 67:16:17. CONCLUSIONS: This study identified an ideally fitting PRS model for identifying and predicting the risk of T2D suitable for the Chinese population. The quantified proportional structure of genetic risk factors, cardiometabolic risk factors, and their interaction was detected, which elucidated the critical effect of genetic factors.

Prevalence and risk factors of metabolic syndrome among adults in Hainan Province / 中国热带医学

@#Abstract: Objective　This study aims to explore the prevalence and risk factors of metabolic syndrome (MS) among the adults in Hainan Province, and to provide scientific basis for MS prevention and control. Methods　A multi-stage cluster random sampling method was applied to select 3 690 permanent residents aged 18 years and above in Hainan Province. The survey was conducted by trained investigators using household appointments and centralized surveys. A questionnaire survey, physical measurement, and laboratory examination were conducted after the collection of blood samples. The processed samples were then tested by a quality-controlled laboratory. Finally, we analysed the prevalence of metabolic syndrome (MS) and its relationship with population characteristics and health-related behaviors. Results　The crude prevalence of MS in the population aged 18 and above in Hainan province was 19.46% and the standardized prevalence was 13.21%, with a higher rate in urban areas (22.21%) than in rural areas (18.13%). The prevalence of MS increased with age (P<0.001), and there were significant differences in MS prevalence among different marital and occupational statuses (P<0.01). Logistic regression results indicated that the age groups of 40-<50 years (OR=2.986, 95%CI:1.355-6.580), 50-<60 years (OR=3.739, 95%CI: 1.715-8.151), 60-<70 years (OR=3.890, 95%CI: 1.769-8.556), 70 years and above (OR=3.927, 95%CI: 1.758-8.771), technical, transportation and production personnel (OR=1.579, 95%CI: 1.033-2.412), retired (OR=1.788, 95%CI: 1.415-2.259), unemployed (OR=1.503, 95%CI: 1.044-2.165), smoking cessation (OR=1.582, 95%CI: 1.162-2.154), insufficient intake of fruits and vegetables (OR=1.196, 95%CI: 1.005-1.422), and insufficient physical activity (OR=1.437, 95%CI: 1.155-1.787) were all associated with the prevalence of MS. Among the investigated subjects, 30.22% of them had one abnormal component, with hyperglycemia being the highest (54.44%); 24.25% of them had two abnormal components, with "hyperglycemia + hypertension" being the highest (33.30%); and 19.46% had three or more components, with "overweight/obesity + hyperglycemia + hypertension" being the highest (24.79%). Conclusions　The prevalence of MS in Hainan Province is on the rise, and effective lifestyle intervention measures are needed to reduce the risk of MS.

Diabetes Complications and Related Comorbidities Impair the Accuracy of FreeStyle Libre, a Flash Continuous Glucose Monitoring System, in Patients with Type 2 Diabetes.

Background: Although flash continuous glucose monitoring systems (FCGM) accuracy has been extensively studied in diabetes, its accuracy is still not fully evaluated in type 2 diabetes (T2D) patients in real-world settings. In the present study, we aim to assess the effects of diabetes complications and related comorbidities on FCGM accuracy in T2D patients with diabetes complications and related comorbidities in the real world. Methods: FCGM data were collected at eight-time points daily (3 AM, 7 AM, 9 AM, 11 AM, 1 PM, 5 PM, 7 PM, and 9 PM) from 742 patients with T2D and compared with simultaneous fingertip capillary blood glucose (reference blood glucose, REF), and the difference was evaluated using Parkes error grid (PEG), surveillance error grid (SEG), and logistic regression analysis. Results: In total, 25,579 FCGM/REF data pairs were included in the study. The FCGM values were lower than the paired REF values in 75% of the pairs. The maximum bias (-23.0%) and maximum mean absolute relative difference (24.5%) were observed at 3 AM among eight-time points. SEG analysis also demonstrated the highest percentage of paired readings in moderate and great risk zone (C and D) at 3 AM than PEG analysis (7.33% vs 0.43%, P<0.001). According to the SEG classification, hypoglycemia, infection, diabetic foot, diabetic ketoacidosis, and hypertension were independent risk factors that impaired FCGM accuracy in patients. Conclusion: FCGM commonly underestimates blood glucose levels. Compared with PEG, SEG analysis seems more conducive to the analysis of FCGM performance. The present data highlights the impairment of diabetes complications and related comorbidities on the FCGM accuracy in T2D patients.

A Novel Method of Clinical Nursing under the Medical Internet of Things Technology.

Internet of things technology began to spread to all industries of our lives; the application of medical internet of things in many hospitals highlighted its advantages and brought a lot of convenience to patients and medical staff. With the continuous progress of China's medical reform and the continuous improvement of patients' requirements for medical service quality, this paper discusses the application of medical internet of things in clinical nursing in ward, and the basic information collection, infusion, and mobile nursing were discussed and studied. Through the parallel control study of the laboratory itself, this paper evaluates whether the two different clinical measurement methods of medical internet of things technology and traditional technology are consistent in body temperature, pulse, respiration, and blood oxygen saturation. At the same time, it also deeply studies the value and advantages of internet of things technology in the application of other monitoring indicators in clinical nursing and analyses the problems in its application. The experimental data show that the two measurement methods with different principles can be completely replaced in clinical application, and the time efficiency of the new clinical nursing method under the medical internet of things technology in mapping body temperature, pulse, and respiration has been improved by 76.20% and 72.02%, respectively, surpassing the traditional information technology and realizing the intelligent, automatic, and standardized data acquisition method. It ensures the authenticity of data and the real-time of information flow and meets the needs of resource sharing and medical regional interconnection.

Clinical interpretation of the flash continuous glucose monitoring data out of range in type 2 diabetes: A real-world study.

AIMS: Flash continuous glucose monitoring system (FCGM) reports nocturnal hypoglycemia with low accuracy in low blood glucose. In our study, we aimed to evaluate the accuracy and clinic profile of FCGM data out of range in T2DM. METHODS: FCGM data out of range were measured in T2DM patients at eight-time points of a day and compared with fingertip capillary blood glucose levels (REFs) as reference values. RESULTS: A total of 307 out-of-range cases from 25,886 paired FCGM/REF data from 742 T2DM patients were evaluated. The distribution of "LO" and "HI" cases displayed the significant difference between eight-time points (P < 0.001) with the highest frequency (6.52%) of the "LO" value at 3 AM. The consistency rate between FCGM "LO" readings and REF < 40 mg/dl was far lower than that of FCGM "HI" readings with REF > 500 mg/dl (0.84% vs. 52.2%). In addition, the frequency of some clinical characteristics, including diabetes duration, hypoglycemia, hypertension, HbA1c, and Hb, were higher in patients with FCGM "LO" readings compared to those with "HI" readings. CONCLUSIONS: These findings suggest the results and treatment regarding FCGM "LO" data should be interpreted with strong caution in the light of the emerging possible adverse measurement in patients.

Incidence of microcarcinoma and non-microcarcinoma in ultrasound-found thyroid nodules.

BACKGROUNDS: The incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort. METHODS: We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations. RESULTS: Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1 % vs. 39.9 %, x2 = 355.69, p = 0.000), smaller size (17.5 ± 9.9 mm vs. 28.0 ± 12.5 mm, t = 23.876 p = 0.000), and higher TI-RADS score (5.5 ± 2.9 vs. 3.4 ± 3.3, t = 18.084, p = 0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2 %) nodules found by ultrasound vs. 68 (3.9 %) by palpation, x2 = 59.737, p = 0.000], and 88 (64.7 %) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3 % (48/136) vs. 16.2 % (11/68), x2 = 8.183, p = 0.004]. CONCLUSIONS: In view of the results observed in our research, malignant nodules were more common in nodules screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We suggest the recommendation against screening thyroid nodules by ultrasound needs to be re-evaluated.

Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma.

Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a unique disease entity within head and neck cancer with rising incidence. Previous work has shown that alternative splicing events (ASEs) are prevalent in HPV+ OPSCC, but further validation is needed to understand the regulation of this process and its role in these tumours. In this study, eleven ASEs (GIT2, CTNNB1, MKNK2, MRPL33, SIPA1L3, SNHG6, SYCP2, TPRG1, ZHX2, ZNF331, and ELOVL1) were selected for validation from 109 previously published candidate ASEs to elucidate the post-transcriptional mechanisms of oncogenesis in HPV+ disease. In vitro qRT-PCR confirmed differential expression of 9 of 11 ASE candidates, and in silico analysis within the TCGA cohort confirmed 8 of 11 candidates. Six ASEs (MRPL33, SIPA1L3, SNHG6, TPRG1, ZHX2, and ELOVL1) showed significant differential expression across both methods. Further evaluation of chromatin modification revealed that ASEs strongly correlated with cancer-specific distribution of acetylated lysine 27 of histone 3 (H3K27ac). Subsequent epigenetic treatment of HPV+ HNSCC cell lines (UM-SCC-047 and UPCI-SCC-090) with JQ1 not only induced downregulation of cancer-specific ASE isoforms, but also growth inhibition in both cell lines. The UPCI-SCC-090 cell line, with greater ASE expression, also showed more significant growth inhibition after JQ1 treatment. This study confirms several novel cancer-specific ASEs in HPV+OPSCC and provides evidence for the role of chromatin modifications in regulation of alternative splicing in HPV+OPSCC. This highlights the role of epigenetic changes in the oncogenesis of HPV+OPSCC, which represents a unique, unexplored target for therapeutics that can alter the global post-transcriptional landscape.