Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Gastroesophageal reflux disease （GERD） is a frequently and commonly occurring disease in clinic. In recent decades， with the development in pathophysiology and drug researches， modern medicine has achieved remarkable progress and results in diagnosis and treatment. However， the treatments for non-erosive reflux disease， refractory gastroesophageal reflux disease， proton pump inhibitor resistance， overlap of disease symptoms， and extraesophageal symptoms are limited and ineffective. Traditional Chinese medicine （TCM） was widely used in clinical practice， which has been proved effective in relieving symptoms and improving the quality of life. Sponsored by China Association of Chinese Medicine （CACM） and undertaken by the Spleen and Stomach Disease Branch of CACM， "the 12^th Youth Salon of Clinical Predominance Disease Series （GERD）" invited 18 authoritative digestive experts of TCM and western medicine to discuss "the difficulties of clinical diagnosis and treatment of GERD and TCM advantages". The focus issues such as modern medical diagnosis and treatment achievements and contributions， improvement and maintenance of symptoms， response to overlapping disease symptoms， reduction and withdrawal of acid suppressors， and treatment of extra-esophageal symptoms were discussed in depth. TCM and western medicine exchanged and complemented each other's strengths， combing the difficulties of modern medical diagnosis and treatment， which clarified the positioning and advantages of TCM and provided guidance for clinical and scientific research.

Objective:To evaluate the effects of hemoclips on preventing delayed bleeding for early gastric cancer (EGC) after endoscopic submucosal dissection (ESD).Methods:Clinical data of 459 patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to August 2020 were collected retrospectively. Patients were divided into group A (hemoclip group, n=162) and group B (non-hemoclip group, n=297) according to whether preventive hemostatic clip treatment was performed after resection. Delayed bleeding within 2 weeks after ESD was observed. Univariate analysis and subgroup analysis were conducted for the delayed bleeding incidence and clinicopathological features. Results:Delayed bleeding incidences of group A and group B were 3.1% (5/162) and 8.1% (24/297) with significant difference between the two groups ( χ2=4.418, P=0.036). Subgroup analysis showed that there were significant differences in the delayed bleeding incidence between the two groups when the diameter of the tumor >20 mm [3.5% (2/57) VS 15.3% (13/85), χ2=5.016, P=0.025], the tumor located in the lower part of the stomach [1.0% (1/97) VS 10.4% (20/192), χ2=8.425, P=0.004], and the depth of tumor invasion was M/SM1 [3.2% (5/157) VS 8.1% (23/285), χ2=4.072, P=0.044]. There were no significant differences in the delayed bleeding incidence between group A and group B when the diameter of the tumor ≤20 mm, the tumor located in the upper/medial part of the stomach and the depth of tumor invasion was SM2 ( P>0.05). Conclusion:Hemoclips can prevent delayed bleeding after ESD for EGC, which is mainly observed in a tumor of diameter >20 mm, located in the lower part of the stomach and M/SM1 tumor invasion. It has little effect on the prevention when the tumor diameter ≤20 mm and located in the upper/medial part of the stomach.

Objective:To evaluate the application of three-dimensional (3D) imaging device to colonoscopy.Methods:A total of 60 patients who underwent painless colonoscopy in Beijing Friendship Hospital, Capital Medical University from November to December, 2019 were enrolled and divided into 2 groups according to random code. Each patient underwent colonoscopy twice, while 2D colonoscopy was used for cecal intubation. Thirty patients were assigned to the experimental group (primary withdrawal used 3D colonoscopy, and secondary withdrawal used 2D colonoscopy), and 30 others to the control group (primary withdrawal used 2D colonoscopy, and secondary withdrawal used 3D colonoscopy). The detection of polyps, the withdrawal time, operating experience, image quality and complication were evaluated in the two groups.Results:The polyp detection rate at the first colonoscopy in the experimental group was 77.3% (17/22), which was higher than 43.5% (10/23) in the control group ( χ2=5.351, P=0.021). Ten operators in the experimental group had dizziness, while the operators in the control group had no dizziness ( P=0.001). There were no significant differences between the two groups in the polyp diameter [0.50 (0.70) cm VS 0.30 (0.20) cm, U=57.000, P=0.170], withdrawal time (4.6±1.5 min VS 5.2±1.9 min, t=-1.189, P=0.239) or image quality (27 cases with 3 points in the identification of lesion nature, and 28 cases with 3 points in the identification of duct both in the two groups, P=1.000) at the first colonoscopy. No complication occurred in either group. Conclusion:Application of 3D imaging device is feasible for colonoscopic polyp detection, and it can be used in clinical practice.

Objective:To analyze the clinicopathological features of de novo early colorectal cancer and to evaluate the efficacy of endoscopic treatment.Methods:Patients with de novo early colorectal cancer who underwent endoscopic resection in Beijing Friendship Hospital, Capital Medical University from June 2020 to May 2022 were enrolled. The baseline data, endoscopic manifestations, treatment methods, postoperative pathological results and prognosis of the patients were collected retrospectively.Results:A total of 33 patients with de novo early colorectal cancer were enrolled with the age of 62.67 ± 8.62 years, and the male to female ratio was 7.25∶1. The long diameter of lesions was 0.96 ± 0.36 cm. The lesion morphology was mainly superficial phenotype (type 0-Ⅱ), accounting for 72.7% (24/33). Endoscopic submucosal dissection (ESD) was performed in 29 cases and endoscopic mucosal resection (EMR) was performed in 4 cases. Postoperative pathology showed that 11 cases (33.3%) were well differentiated tubular adenocarcinoma, of which the superficial submucosal layer was invaded in 2 cases. Twenty cases (60.6%) were moderately differentiated tubular adenocarcinoma, of which the superficial submucosa layer was invaded in 5 cases and the deep submucosa layer in 15 cases. Two cases (6.1%) were moderately-poorly differentiated tubular adenocarcinoma, where the deep submucosa layer was invaded in both. There was significant correlation between the depth of invasion and the degree of differentiation ( P<0.001), and moderately and moderately-poorly differentiated lesions were more likely to invade the deep submucosa layer. The en bloc resection rate was 100.0% (33/33), the complete resection rate was 97.0% (32/33), and the curative resection rate was 42.4% (14/33). Among the 19 patients who did not achieve curative resection, 13 patients received supplementary surgical treatment. No tumor residue or lymph node metastasis was found in the postoperative pathology. All patients were followed up for 3-25 months, and no signs of local recurrence or metastasis were found. Conclusion:Most de novo early colorectal cancers are superficial phenotype under endoscopy. The pathology is mainly moderately differentiated tubular adenocarcinoma. Endoscopic resection of de novo early colorectal cancer shows encouraging short-term efficacy.

As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.
Single-Domain Antibodies

Objective:To determine the accuracy and influencing factors for endoscopic ultrasound (EUS) in predicting the invasive depth of early gastric cancer (EGC).Methods:A retrospective analysis was conducted on data of patients with EGC who were staged T1 with EUS and were treated at Beijing Friendship Hospital from January 2014 to August 2020. The consistency between the invasive depth determined by EUS and postoperative pathology were compared, and the accuracy, the sensitivity and the specificity of EUS were calculated. Logistic regression model was used for univariate and multivariate analysis to explore the relevant factors that affected the accuracy of EUS.Results:A total of 380 lesions were included. While 301 intramucosal (T1a) lesions and 79 submucosal (T1b) lesions were detected with EUS, postoperative pathology diagnosed 320 T1a lesions and 60 T1b lesions. The accuracy of EUS in predicting the invasive depth of EGC was 77.1% (293/380), the sensitivity and the specificity were 83.4% (267/320) and 43.3% (26/60) respectively. Multivariate analysis indicated that the lesions located in the upper 1/3 of the stomach ( OR=2.272, 95% CI: 1.266-4.080, P=0.006), ≥20 mm in size ( OR=2.013, 95% CI: 1.200-3.377, P=0.008) and poorly differentiated cancer ( OR=2.090, 95% CI: 1.018-4.294, P=0.045) were the independent risk factors affecting the accuracy of EUS. Poorly differentiated EGC ( OR=4.046, 95% CI: 1.737-9.425, P=0.001) was the risk factor for over-staging of EUS. Conclusion:EUS is useful in predicting the invasive depth of EGC. Factors affecting the accuracy of EUS include location in the upper 1/3 of the stomach, ≥20 mm in size and poorly differentiated EGC. Additionally, poor differentiation is the risk factor for over-staging of EUS.

Objective:To evaluate the efficacy and safety of SPOT (GI Supply, USA), a new carbon-based permanent marker approved by the Food and Drug Administration (FDA), in the endoscopic marking for gastrointestinal lesions.Methods:A total of 115 patients with gastrointestinal lesions who underwent endoscopic treatment or surgery in Beijing Friendship Hospital or Beijing Chao-Yang Hospital from April 2019 to November 2019 were enrolled in the study. SPOT was used to mark the lesions, and marking points were found during endoscopic treatment or surgery to calculate the effective marking rate by single-group target value method. Adverse events after marking were recorded, and the changes of blood routine test, liver and kidney functions before and after marking were compared.Results:The effective rate of endoscopic marking with SPOT was 99.13% (114/115). The longest marking time was 57 days. There was no puncture of intestinal wall or injection into abdominal cavity during the marking process. One patient developed mild fever after marking. The incidence of adverse events was 23.48% (27/115), which were all unrelated to the test equipment. There was no significant difference in blood routine tests or liver and kidney functions before and after marking ( P>0.05). Conclusion:SPOT produced by GI Supply can effectively mark gastrointestinal lesions without serious adverse events, which meets the requirements of clinical use.

To investigate the clinical and endoscopic characteristics and endoscopic treatment efficacy of cap polyposis, data of 14 patients (56 polyps) who were histologically diagnosed as having cap polyposis after endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) in Beijing Friendship Hospital from June 2017 to February 2021 was retrospectively analyzed. Of the 14 patients, 8 were males and 6 were females. The age ranged from 14 to 74 years, including 7 cases of <60 years old and 7 cases of ≥60 years old. 7 patients (50.0%) had clinical manifestations. Four cases had multiple polyps and 10 cases (71.4%) had single polyps. There were 42 polyps (75.0%) located in the rectum, 13 (23.2%) in the sigmoid colon and 1 in the transverse colon. According to the classification of Yamada, 44 polyps (78.6%) were type Ⅰ, 3 polyps were type Ⅱ, 5 polyps were type Ⅲ and 4 polyps were type Ⅳ. Under endoscopy, there were 41 polyps (73.2%) with obvious white cap-like coverings on the surface and 23 polyps with obvious hyperemia and redness on the mucosa, 8 of which were both visible. Two cases were treated with ESD and 12 cases were treated with EMR, all of which were completely excised. No bleeding, perforation, infection or other complications occurred during and after operation. The clinical symptoms of 7 patients were relieved. During the follow-up period, 11 cases (78.6%) completed colonoscopy, and no polyp recurrence was found. In conclusion, there is no gender or age difference in patients of cap polyposis. It is usually single and located in the rectum and sigmoid colon with Yamada type Ⅰ. The surface of lesions is mostly covered with white cap. Patients may have no obvious clinical symptoms. Treatment of ESD and EMR is safe and effective for cap polyposis.

Objective:To investigate the clinicopathological features of missed synchronous multiple early gastric cancer (SMEGC).Methods:Clinical and pathological data of 10 missed SMEGC patients in Beijing Friendship Hospital collected from January 2015 to December 2019 were reviewed for the clinicopathological and endoscopic features.Results:Ten missed SMEGC patients were all over 60 years old, and 6 of them were males. Six patients had family history of tumor and 6 had comorbidity (hypertension, diabetes, dyslipidemia, cardiovascular or cerebrovascular diseases). In terms of endoscopic and pathological manifestations, missed lesions of 6 cases were not smaller than the initial lesions, and more than half of the missed lesions had the same vertical location in the stomach (6/10), infiltration depth (8/10), histological classification (9/10), atrophic (8/10) and intestinal metaplasia (8/10) as the initial lesions.Conclusion:Physicians should be aware of the possibility of missed lesions during the first endoscopic treatment and the follow-up, especially at the same vertical location of the initial lesions in elderly males with family history of tumor and comorbidity.