OBJECTIVE: N6-methyladenosine (m ⁶A) is a common epigenetic modification in eukaryotes. In this study, we explore the potential impact of m ⁶A-associated single nucleotide polymorphisms (m ⁶A-SNPs) on heart failure (HF). METHODS: Data from genome-wide association studies (GWAS) investigating HF in humans and from m ⁶A-SNPs datasets were used to identify HF-associated m ⁶A-SNPs. Their functions were explored using expression quantitative trait locus (eQTL), gene expression, and gene enrichment analyses. Mediation protein quantitative trait locus (pQTL)-Mendelian randomization (MR) was used to investigate the potential mechanism between critical protein levels and risk factors for HF. RESULTS: We screened 44 HF-associated m ⁶A-SNPs, including 10 m ⁶A-SNPs that showed eQTL signals and differential expressions in HF. The SNP rs1801270 in CDKN1A showed the strongest association with HF ( P = 7.75 × 10 ^-6). Additionally, MR verified the genetic association between the CDKN1A protein and HF, as well as the mediating effect of blood pressure (BP) in this pathway. Higher circulating level of CDKN1A was associated with a lower risk of HF (odds ratio [ OR] = 0.82, 95% confidence interval [ CI]: 0.69 to 0.99). The proportions of hypertension, systolic BP, and diastolic BP were 48.10%, 28.94%, and 18.02%, respectively. Associations of PDIA6 ( P = 1.30 × 10 ^-2) and SMAD3 ( P = 4.80 × 10 ^-2) with HF were also detected. CONCLUSION Multiple HF-related m ⁶A-SNPs were identified in this study. Genetic associations of CDKN1A and other proteins with HF and its risk factors were demonstrated, providing new ideas for further exploration of the molecular mechanisms of HF.
Humans ; Polymorphism, Single Nucleotide ; Heart Failure/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cyclin-Dependent Kinase Inhibitor p21/metabolism* ; Quantitative Trait Loci ; Adenosine/metabolism* ; Male ; Female ; Genetic Predisposition to Disease

Objective:To evaluate the new model of group screening combined with opportunistic screening for the diagnosis and treatment of gastric cancer.Methods:Group screening combined with opportunistic screening was used for gastric cancer screening. (1) Group screening. Cluster sampling was used to screen gastric cancer by endoscopy in high-risk population (aged 40-<70 years) of rural residents in Weihai from July 2017 to December 2020, and biopsy was obtained for histopathology if necessary. Main collection parameters included the detection rate of advanced gastric cancer, early gastric cancer and high-grade intraepithelial neoplasia (HGIN). (2) Opportunistic screening. The changes of the detection rates of early gastric cancer in opportunistic screening in 2 hospitals in Weihai area were observed during the same period of time.Results:(1) In group screening, from July 2017 to December 2020, the first batch of 8 000 cases of gastric cancer screening were completed. The cases of advanced gastric cancer, early gastric cancer and HGIN were 36, 28, and 62, respectively. The detection rates of gastric cancer and early gastric cancer were 0.80% (64/8 000) and 43.75% (28/64), respectively. The proportion of early gastric cancer+HGIN who received endoscopic submucosal dissection (ESD) was 77.78% (70/90), and the rate of curative resection was 100.00%(70/70). (2) Opportunistic screening: from July 2017 to December 2020, the annual early gastric cancer detection rates in opportunistic screening in Wendeng District Traditional Chinese and Western Medicine Hospital were 16.67% (1/6), 20.00% (3/15), 23.53% (4/17), and 33.33% (6/18) in the consecutive 4 years, respectively. The annual detection rates of early gastric cancer in opportunistic screening in Ru Shan Peoples Hospital were 14.74% (14/95), 23.80% (60/252), 25.49% (65/255), and 24.04% (50/208), respectively. The detection rates of opportunistic screening for early gastric cancer in hospitals in Weihai city increased year by year.Conclusion:In areas with high incidence of gastric cancer, a certain scale of group screening can lead to a wider range of opportunistic screening, resulting in the increase of the detection rate of early gastric cancer. The new model of diagnosis and treatment of gastric cancer is worth recommendation.

Objective    To investigate the clinical value of artificial intelligence (AI)-assisted chest computed tomography (CT) in the diagnosis of peripheral lung shadow. Methods    The CT image data of 810 patients with peripheral pulmonary shadow treated by thoracic surgery in Tianjin Chest Hospital Affiliated to Tianjin University from January 2018 to July 2019 were retrospectively analyzed using AI-assisted chest CT imaging diagnosis system. There were 339 males and 471 females with a median age of 63 years. The malignant probability of preoperative AI-assisted diagnosis of peripheral pulmonary shadow was compared with the results of postoperative pathology. Results    The pathological diagnosis of 810 patients with peripheral pulmonary shadow was lung cancer in 627 (77.4%) patients, precancerous lesion in 30 (3.7%) patients and benign lesion in 153 (18.9%) patients. The median probability of malignant AI diagnosis before operation was 86.0% (lung cancer), 90.0% (precancerous lesion) and 37.0% (benign lesion), respectively. According to the analysis of receiver operating characteristic (ROC) curve of AI malignant probability distribution in this group of patients, the area under the ROC curve was 0.882. The critical value of malignant probability for diagnosis of lung cancer was 75.0%with a sensitivity of 0.856 and specificity of 0.814. A total of 571 patients were diagnosed with AI malignancy probability≥ 75.0%, among whom 537 patients were pathologically diagnosed as lung cancer with a positive predictive value of 94.0%(537/571). Conclusion    The AI-assisted chest CT diagnosis system has a high accuracy in the diagnosis of peripheral lung cancer with malignant probability≥75.0% as the diagnostic threshold.

Objective:To explore the clinical significance of recurrent laryngeal nerve inlet zone(RLNIZ) lymph node metastasis in papillary thyroid cancer(PTC).Methods:The clinical data of the clinicopathologic characteristics of 738 cases with papillary thyroid cancer at our centers from Jul 2017 to Jun 2018 was retrospectively reviewed. 108 cases with RLNIZ lymph node dissection for pathological examination were included. The relationship between metastasis of RLNIZ lymph node and clinicopathologic characteristics was analyzed.Results:RLNIZ lymph node was detected in 12.3%(91/738)cases, the mean lymph node number in RLNIZ was 1.5±0.7, and 30.8%(28/91) cases suffered RLNIZ lymph node metastasis. RLNIZ lymph node metastasis(LNM) is associated with tumor size( P=0.028), capsular invasion( P=0.019), No. of central compartment LNM( P<0.001) and lateral neck LNM( P<0.001). No. of central compartment LNM was found to be the independent risk factor of RLNIZ lymph node metastasis. The incidence of dysphagia and inferior parathyroid damage was 0.9%(1/108)respectively. Conclusions:RLNIZ lymph node metastasis is common among PTC patients , therefore, RLNIZ lymph node should be routinely removed especially in patients with tumor size over 1cm、suspected capsular invasion and lateral neck lymph node metastasis confirmed by preoperative imaging examination.

Objective:To explore the expression and clinical significance of miR-143 in papillary thyroid cancer (PTC) .Methods:Tumor samples and adjacent tissues from 52 patients with PTC were obtained from Jan. 1st, 2018 to Mar. 31st, 2018 in Thyroid Surgery Department of the Affiliated Yantai Yuhuangding Hospital of Qingdao University. Quantitative reverse-transcriptase PCR (RT-qPCR) was used to measure the expression of miR-143 in those subjects. In addition, the relationship between the expression levels of miR-143 and the clinicopathological characteristics was analyzed.Results:RT-qPCR indicated that the expression of miR-143 was down-regulated in PTC, which was significantly lower than that in adjacent tissues ( t=-21.39, 95% CI: 18.20-15.07, P<0.001) . Low expression of miR-143 was related to the number of lymph node metastasis ≥3 in central compartment ( t=10.13, P=0.012) and lateral neck lymph node metastasis ( t=-4.67, P<0.001) . Conclusion:Downregulation of miR-143 in PTC is linked to the metastasis of PTC and may be a potential target for therapeutic intervention.

Objective: To investigate the application value of Information-Motivation-Behavioral Skill Model (IMB)-based continuing care on the recovery of nerve function and life quality in patients with stroke after thrombolytic therapy. Methods: Stroke patients who underwent thrombolytic therapy were randomly assigned to IMB group(35 cases) and control group(35 cases) according to the method of random number table. The control group recieved routine thrombolysis nursing, IMB group was given IMB-based continuing care. After six months of intervention, nerve function was evaluated by National Institute of Health Stroke Scale(NIHSS) and Modified Rankin Scale(MRS), the active ability was performed by Fugl-Meyer Assessment Scale(FMA) and Barthel Index(BI), the quality of life was assessed by the item short from health survey(SF-36), respectively. Results: Before intervention, the scores of NIHSS, MRS, FMA, BI, SF-36 between two groups was no significant difference (P>0.05). After three and six months of nursing, the NIHSS, MRS was (7.84±2.20), (5.00±1.60) points and (3.48±0.84), (3.07±0.69) points in IMB group, and (9.75±1.82), (8.21±1.37) points and (4.06±1.08), (3.91±0.71) points in control group, there was significant difference between two groups (t =2.417-8.647, P<0.01 or 0.05). After one, three and six months of intervention, FMA was (65.86±5.67), (76.41±8.47), (78.79±8.58) points, BI was (46.29±7.29), (58.09±10.20), (67.50±9.44) points, SF-36 was (33.13±4.64), (43.09±6.70), (49.83±8.56) points in IMB group, (58.53±8.92), (64.47±7.56), (71.81±8.90) points, (42.47±5.67), (48.74±5.39), (56.03±6.55) points and (29.63±4.06), (35.91±5.93), (41.02±9.05) points in control group, there was significant difference between two groups (t =2.333-5.972, P< 0.05). Moreover, in the repeated measures ANOVA showed the differences of NIHSS, MRS, FMA, BI, SF-36 were statistically significant for the group by time interaction(F=13.556-133.994, P<0.05). Conclusions IMB-based continuing care can promotes the recovery of nerve function and improves the quality of life in patients with stroke after thrombolytic therapy.

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.
Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genome-Wide Association Study ; Humans ; Infant ; Logistic Models ; Machine Learning ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Retinol-Binding Proteins, Plasma ; genetics ; Risk Assessment

Objective To evaluate the value of ultrasound-guided nasotracheal intubation in the patients undergoing oral maxillofacial surgery by comparing with blind intubation.Methods Forty ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 18-75 yr,weighing 45-90 kg,scheduled for elective oral maxillofacial surgery,were randomly divided into blind intubation group (group B,n =20) and ultrasound group (group U,n =20) according to a random number table.Nasotracheal intubation was performed after routine topical analgesia and conscious sedation.The front end of catheter was adjusted to the aditus glottidis according to the sound of respiratory air,and tracheal intubation was placed when the strongest inspiratory phase appeared in group B.A linear array probe (frequency 7-15 MHz) was used,and the images of glottis expansion and wired catheter insertion were visualized in the thyroid cartilage window in U group.Before intubation and at 0,1,3 and 5 min after successful intubation,mean arterial pressure (MAP),HR and SpO2 were recorded.The development of responses to intubation was recorded during intubation.The successful intubation at first attempt,the number of intubation,intubation time,and postoperative complications such as sore throat or hoarseness were recorded.Results Compared with group B,the number of intubation was significantly reduced,intubation time was shortened,the rate of successful intubation at first attempt was increased,the failure rate of intubation and incidence of sore throat and hoarseness were decreased,and no significant changes were found in the parameters of hemodynamics and incidence of responses to intubation in group U.No intraoperative awareness of intubation occurred in patients.Conclusion Compared with blind intubation,ultrasound-guided nasotracheal intubation can raise the probability of successful intubation at first attempt,reduce the number of intubation,and shorten intubation time,and it is safe and convenient and provides significant value clinically for the patients undergoing oral maxillofacial surgery.

Objective To study the change of the oxygen-carried function of stored red blood cells,which was warmed in room temperature and calorstat.Methods Randomly removed from 4 ℃storage refrigerator,red blood cell suspension were put in room temperature 30 min (group N)and 37℃ calorstat 30 min (group H),and samples taken to examine electrolyte,blood gas,free Hb,ATP content,2,3-DPG content,oxygen affinity(P50).Results In two groups,blood pH value and blood Na+ did not change obviously due to heating.The content of blood K+ and free Hb increased,glucose fell,but there was no statistically significant difference.The content of ATP and 2,3-DPG in eryth-rocyte increased and P50 increased after heating (P <0.05),which increased more significantly in group H compared with group N (P<0.05).Conclusion Heating stored blood up to 37 ℃ can in-crease the oxygen-carried function of red blood cells,which contribute to improve the effectiveness of transfusion.