Objective To detect the effective connectivity of resting- state functional magnetic resonance imaging (fMRI) in normal adults. Methods 36 normal adults were performed resting-state fMRI scanning, and 5 brain netwokes were included as regions of interests. Independent component (ICA) was used to evaluate the effective connectivity, and multivariate Granger causality analysis (mGCA) was used to analyze the casuality between the networks. All preprocessing steps were carried out using Statistical Parametric Mapping 5.0 software. Results 5 classic resting brain networks including default mode network (DMN), memory network (MeN), motor network (MoN), auditory network (AN) and executive control network (ECN) were aquired. The mGCA presented significant casuality between DMN and other 4 networks, MeN and ECN, AN and MoN, ECN and AN. Conclusion There are specific brain effective connectivity of resting-state fMRI in normal adults, and there is significant causal link between these networks.

Objective:To evaluate the diagnostic value of endoscopic ultrasonography (EUS) in colorectal submucosal lesions, and provide evidence for clinical diagnosis and treatment strategies.Methods:A retrospective analysis was performed on data of 229 patients with colorectal submucosal lesions discovered by electronic colonoscopy and EUS. The diagnosis was confirmed by pathology. The location, type, EUS features of lesions and the coincidence rate of EUS and histopathological diagnosis were analyzed.Results:Colorectal submucosal lesions were common in the rectum (44.98%, 103/229) and ascending colon (15.28%, 35/229). Lipoma was the most common pathological type of colorectal submucosal lesions (34.93%, 80/229), which was commonly located in transverse colon (22.50%, 18/80) and ascending colon (20.00%, 16/80). Neuroendocrine tumor was the second one, accounting for 33.63% (77/229), and was commonly located in rectum (96.10%, 74/77), followed by cyst (18.78%, 43/229). Under EUS, 229 cases of lesions originated from submucosa in 215 cases, muscularis mucosa in 11 cases, and muscularis propria in 3 cases. The overall coincidence rate of EUS and pathological diagnosis was 89.08% (204/229). The coincidence rate of EUS diagnosis was 100.00% (80/80) for lipoma, 5/5 for air-cyst, 3/3 for intestinal stromal tumor, 81.82% (72/88) for neuroendocrine tumor, 89.13% (41/46) for cyst, 1/4 for leiomyoma, 2/5 for lymphangioma, and granulosa cell tumor and neurofibroma were both 0.Conclusion:EUS has a more accurate diagnosis of the origin, echogenicity and pathological properties of colorectal submucosal lesions, but it has certain limitations for the diagnosis of rare tumors such as granulosa cell tumor and neurofibroma.

Objective: To explore the association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease (CHD). Methods: A total of 784 patients with CHD were consecutively enrolled at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. According to thyroid function test results, patients were divided into hypothyroidism group (79 cases) and non-hypothyroidism group (705 cases). All patients had undergone sleep monitoring. The sleep apnea status was compared between the two groups. Multivariate logistic regression and linear regression models were used to analyze the association between hypothyroidism and sleep breathing disorders in patients with CHD. Results: The proportion of females, mean body weight and body mass index in the hypothyroidism group were higher than those in the non-hypothyroidism group [26.6% vs.16.2%, (78.6±11.6) kg vs. (75.7±12.0) kg, (27.7±3.2) kg/m² vs. (26.6±3.5) kg/m², all P<0.05]. Patients in hypothyroidism group had a decreased average oxygen saturation (SaO₂) compared with patients in non-hypothyroidism group [ (93.2±2.9) % vs. (93.9±2.0) %, P=0.030]. In addition, events of hypoventilation in hypothyroidism group were significantly higher than those in non-hypothyroidism group[92.5 (45.8, 758.3) times vs. 68.0 (33.0, 125.0) times, P=0.013]. There were no significant differences in apnea hypopnea index, diagnosis of obstructive sleep apnea and other sleep breathing parameters between the two groups (P>0.05). A multiple linear regression analysis found that in patients with CHD, the correlation between hypothyroidism and average sleep SaO₂ was significant (β=-0.508, 95%CI -0.989--0.026, P=0.039). Conclusions: CHD patients with hypothyroidism had a lower sleep average SaO₂, and a higher sleep hypopnea events. There is a correlation between hypothyroidism and sleep hypoxia in patients with CHD. Clinical trial registration clinicalTrials.gov, NCT03362385.

Objective: To investigate the impact of moderate/severe obstructive sleep apnea (OSA) on the prognosis of acute myocardial infarction. Methods: We prospectively selected patients with acute myocardial infarction (AMI) who were hospitalized at the Emergency Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. Patients who met the inclusion criteria were examined with portable sleep respiration monitoring. Patients were divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 beats/hour) and no/mild OSA group (AHI<15 beats/hour) according to sleep AHI. The incidence of major adverse cerebrovascular events (MACCE) after discharge was compared between the two groups, and the independent risk factors of MACCE were analyzed. Results: A total of 432 patients were enrolled in this study, including 211 moderate/severe OSA patients (48.8%). Compared with no/mild OSA group,patients with moderate/severe OSA had higher body mass index ((27.17±3.22) kg/m² vs. (25.55±3.44) kg/m², t=-5.033,P<0.001), higher proportion of history of percutaneous coronary intervention (PCI) (18.5%(39/211) vs. 8.6%(19/221), χ²=9.076,P=0.003), and higher proportion of 3-vessel disease (31.3%(66/211) vs. 24.9%(55/221), χ²=10.196,P=0.017). The median follow-up time was 1.0 (0.7, 1.7) years. The incidence of MACCE in the moderate/severe OSA and no/mild group was 19.9%(42/211) and 11.3%(25/221), respectively. Kaplan-Meier analysis showed a higher cumulative risk of MACCE in patients with moderate/severe OSA (log-rank test,χ²=5.467, P=0.019). Multivariate Cox regression analysis showed that moderate/severe OSA (HR=1.915, 95%CI 1.016-3.611, P=0.045) and diabetes mellitus (HR=1.819, 95%CI 1.022-3.238, P=0.042) were independent risk factors for MACCE at 1 year post discharge in patients with AMI. Conclusions: Nearly half of AMI patients are complicated with moderate/severe OSA in this patient cohort. Coronary artery disease is more severe in AMI patients complicating with moderate/severe OSA. Moderate/severe OSA is an independent risk factor for MACCE at 1 year after discharge in patients with AMI. Whether the prognosis of AMI can be improved by intervention of OSA remains to be investigated. Trial Registration Clinical Trial.gov, NCT03362385.

Objective To investigate the effectiveness and safety of endoscopic mucosal resection with precutting(EMR-P)for the treatment of rectal neuroendocrine neoplasm(RNEN)smaller than 1 cm in diameter.Methods Clinical data of 177 patients with RNEN smaller than 1 cm in diameter from December 2016 to December 2021 were retrospectively analyzed.According to different treatment protocols,177 patients with RNEN were divided into endoscopic mucosal resection(EMR)group(n = 46),EMR-P group(n = 40)and endoscopic submucosal dissection(ESD)group(n = 91).The en bloc resection rate,complete resection rate,operation time,postoperative hospitalization time and incidence of operative complications among the three groups were compared.Results The complete resection rate in the EMR-P group(95.0%)and ESD group(97.8%)were significantly higher than that in the EMR group(87.0%)(P<0.05);The operation time in the EMR-P group(9.86±2.23)min was longer than that in the EMR group(4.12±0.88)min,EMR-P group and EMR group were shorter than that in the ESD group(19.55±3.67)min,the difference was statistically significant(P<0.05);Postoperative hospitalization time in the EMR group was(2.45±0.29)d and EMR-P group was(2.43±0.23)d,which were shorter than that in the ESD group(3.30±0.32)d,and the difference was statistically significant(P<0.05).There were no significant difference in the rates of en bloc resection and operative complications among the three groups(P>0.05).Conclusion EMR-P for the treatment of RNEN<1 cm in diameter has the advantages,such as simple operation,short operation time and hospitalization time,high histological complete resection rate and low complication rate,which is worthy of clinical application.

Objective To examine the prevalence of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS),and to evaluate the relationship of OSA with inflammatory biomarkers in ACS patients.Methods Patients with ACS treated at Beijing Anzhen Hopital from June 2015 to May 2017 were enrolled.Subjects were evaluated for OSA by sleep study,and were divided into a normal-mild OSA group (Apnea Hypopnea Index,AHI ＜ 15 times/h) and a moderate-severe OSA group (AHI ≥ 15 times/h).Laboratory examination and sleep study were monitored to analyze the effects of OSA on biomarkers by LSD-t test,Mann-whitney U test,or Chi-square test.Correlation analysis was performed to analyze the association of OSA with high sensitivity C-reactive protein (hs-CRP) by Spearman correlation anaylsis.Results A cohort of 836 patients with ACS were enrolled including 408 patients in the normal-mild OSA group and 428 patients in the moderate-severe OSA group.The levels of leukocyte(x 109L) [7.78 (6.33,9.86) vs 7.29 (6.01,9.16),P=0.006],neutrophils(× 109L) [5.05 (3.84,7.23)vs 4.80 (3.74,6.66),P=0.044],monocytes(x 109L) [0.42 (0.33,0.54) vs 0.39 (0.31,0.51),P=0.033],hsCRP(mg/L) [3.18 (1.10,11.52) vs 1.78 (0.65,6.46),P＜0.01],fibrinogen(g/L) [3.17 (2.87,3.74) vs 2.97 (2.59,3.50),P=0.002],and uric acid(μmol/L) [360 (302,422) vs 341(283,407),P=0.006] in the moderatesevere OSA group were significant higher than those in the normal-mild OSA group.AHI (correlation coefficient=0.171,R2=0.020,P＜0.01),ODI (correlation coefficient =0.201,R2=0.027,P＜0.01),and TSaO2 ＜ 90％ (correlation coefficient =0.105,R2=0.005,P＜0.01) were positively correlated with hs-CRP;minimal SaO2 (correlation coefficient=-0.100,R2=0.001,P=0.008) and mean SaO2 (correlation coefficient =-0.127,R2=0.006,P＜0.01) were negatively correlated with hs-CRP.Conclusions For patients with ACS,the level of inflammatory markers in the moderate-severe OSA group is significantly higher than that in the normal-mild OSA group.Hs-CRP is significantly associated with the severity of OSA.Diagnosis and monitoring of OSA should be considered in ACS management in the future.

Objective To investigate the clinical efficacy of Baduanjin combined with biofeedback on functional defecation disorders and the effect on serum brain-gut peptide.Methods From June, 2017 to February, 2018, 68 patients were randomly divided into control group (n=34) and observation group (n=34). Both groups received biofeedback therapy, and the observation group took the training of Baduanjin in addition, for twelve weeks. Then, their overall clinical efficacy, main syndrome score of constipation, the score of Patient Assessment of Constipation Quality of Life (PAC-QOL) and Brain-gut peptide level were compared before and after intervention.Results The total clinical efficacy was higher in the observation group than in the control group (Z=-2.065, P=0.039) without shedding cases. After treatment, the main symptoms of constipation significantly improved (t>2.162, P<0.05) in both groups, while the defecation inactivity, defecation time and abdominal distension score were significantly lower in the observation group than in the control group (t>2.837, P<0.01), as well as the defecation strain (t=-2.070, P<0.05); the score of PAC-QOL decreased (t>2.085, P<0.05) in both groups, and was lower (t=-2.243, P<0.05) in the observation group than in the control group; the level of serum 5-hydroxytryptamine (5-HT), nitric oxide (NO) and vasoactive intestinal peptide (VIP) decreased (t>2.420, P<0.05), while the level of serum substance P (SP) increased (t>6.780, P<0.001), the level of serum 5-HT, serum NO and serum VIP was lower (t>2.039, P<0.05), and the level of serum SP was higher (t=3.500, P<0.001) in the observation group than in the control group.Conclusion Baduanjin combined with biofeedback can improve the clinical efficacy of patients with functional defecation disorders, and its mechanism is closely related to the regulation of abnormal secretion and the expression of brain-gut peptide.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.