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.

Objective:To translate the English version of the Questionnaire Assessing the Childbirth Experience (QACE) into Chinese and test its reliability and validity, enriching the evaluation tools used for delivery experience in China, providing guidance for medical personnel to evaluate the delivery experience of mothers, and providing reference for improving the delivery experience of mothers in the future.Methods:Based on Beaton ′s cross-cultural debugging guide, the Chinese version of QACE was developed, including correct translation, comprehensive, back translation, expert consultation and pre-test. The reliability and validity of the questionnaire survey was carried out on 235 participants who visited the postpartum clinic in West China Second Hospital, Sichuan University and Mianyang Central Hospital. Results:In 235 participants, aged 20-29 years old with 79 cases, aged 30-39 years old with 152 years old, aged 40-43 years old with 4 cases. The Chinese version of QACE consisted of 4 dimensions (emotional state, relationship with medical staff, first time spent with newborns, and feelings after 1 month postpartum) and 13 items. The Cronbach α coefficient of the scale was 0.812, the Cronbach α coefficient of each dimension was 0.661-0.844, and the broken half reliability was 0.527. The scale level content validity index was 0.95. Four common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 67.682%. Conclusions:The Chinese version of QACE has significant reliability and validity, and can be used to evaluate maternal delivery experiences.

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.

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.

Mycoplasma pneumoniae is the most common pathogen of respiratory tract infection in children and adults. Clinical observation shows that M. pneumoniae infection can cause massive mucus secretion in the respiratory tract, which makes the breathing of patients difficult. Studies have shown that M. pneumoniae infection can cause massive secretion of mucin 5AC (MUC5AC). Adhesin P1 plays an important role in the pathogenesis of M. pneumoniae infection by mediating the adhesion of pathogens to host cells, and the C-terminal residues of P1 (P1-C) are immunogenic. This study investigated the molecular mechanism of Wnt/β-catenin signaling pathway inhibitor Dickkopf-1 (DKK1) in the secretion of MUC5AC in mouse airway epithelial cells (MAECs) induced by P1-C. Scanning electron microscope and hematoxylin-eosin staining were used to observe the effect of P1-C on mucus secretion of MAECs. Protein chip was used to detect the secretion of cytokines and analyse the enrichment of related signaling pathways induced by P1-C in MAECs. Periodic acid schiff stain (PAS) staining, Tunel staining and Masson staining were used to detect the damage of the lungs of mouse exposed to P1-C. Immunohistochemistry was used to detect the secretion of MUC5AC expression, and Western blotting was used to reveal the molecular mechanism of DKK1-regulated secretion of MUC5AC induced by P1-C protein in MACES. The results showed that P1-C induced the massive secretion of mucus and inflammatory factors in MAECs. During P1-C infection, DKK1 down-regulated janus kinase 2 (JAK2), phosphorylation signaling and transcription activator 1 (p-STAT1) and phosphorylation signaling and activator of transcription 3 (p-STAT3) expression. Overexpression of DKK1 significantly up-regulated the expression of MUC5AC repressor transcription factor fork-head box protein A2 (FOXA2). At the same time, the expression of MUC5AC induced by P1-C was inhibited significantly. It is speculated that DKK1 can effectively reduce the secretion of MUC5AC in MAECs induced by P1-C by inhibiting the JAK/STAT1-STAT3 signaling pathway and up-regulating the expression of FOXA2.
Animals ; Mice ; Epithelial Cells ; Lung ; Mucin 5AC/metabolism* ; Mycoplasma pneumoniae/metabolism* ; Signal Transduction

ObjectiveTo estimate the total effect size and the proportion of contextual effect (PCE) of non-surgical treatments for rotator cuff injury. MethodsRandomized controlled trial (RCT) on non-surgical treatments for rotator cuff injuries was retrieved from PubMed, Embase, Cochrane Library, Web of Science, CINAHL, CNKI, and Wanfang Data from the establishment to October, 2020. Two researchers conducted independent literature screening, data extraction and quality evaluation, and used STATA 15.0 software for meta-analyses. ResultsForty studies involving 2 976 participants were included. The total PCE of pain was 0.61 (95% CI 0.54 to 0.69). PCE of treatments from the largest to the smallest were corticosteroid injection, extracorporeal shockwave therapy, oral non-steroidal anti-inflammatory drugs (NSAIDs), manual therapy, hyaluronic acid injection therapy, platelet-rich plasma injection therapy, laser therapy, NSAIDs injection therapy, and acupuncture therapy. Total PCE for function and range of motion was 0.69 (95% CI 0.61 to 0.77) and 0.62 (95% CI 0.48 to 0.81), respectively. Blinding, studies in developed countries, and longer courses of treatment increased the PCE of pain. ConclusionUp to 61% of PCE for the non-surgical treatments for rotator cuff injuries means instable research. A higher proportion of PCE may be the cause of inconsistencies between clinical practice and clinical research conclusions.

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.