ObjectiveTo understand the current situation and hot spots of research on the treatment of constipation by traditional Chinese medicine （TCM） in China and foreign countries， and provide references and directions for future research. MethodIn this study， the data analysis software CiteSpace 5.8.R3C was used to conduct bibliometrics analysis of the relevant papers on the treatment of constipation by TCM from January 1， 2000 to December 31， 2021 in China National Knowledge Infrastructure （CNKI） and Web of Science core database. The visual display was carried out. ResultAfter retrieval， 2 133 papers were included in CNKI database and 224 papers were included in Web of Science core database. The statistical analysis showed that the overall annual publication volume in China and foreign countries was on the rise， but the publication volume in China had been declining for the past two consecutive years. The author co-occurrence analysis showed that the authors with the largest number of publications in China and foreign countries were LIU Chunqiang and CHUNGWAH CHENG， respectively. The institution co-occurrence analysis showed that the institutions with the largest number of publications in China and foreign countries were the Anorectal Department of Longhua Hospital Affiliated to Shanghai University of TCM and Beijing University of Chinese Medicine， respectively. The keyword analysis showed that research in this field in China and foreign countries mainly focused on TCM therapy， clinical research， etiology and pathogenesis， etc. ConclusionThe research on the treatment of constipation by TCM is mainly concentrated in China， but there is no closely-related scientific research team. The research in this field in China and foreign countries is still developing. With the continuous deepening of research， all research institutions should pay attention to interdisciplinary intersection， highlight technological innovation， and strive to achieve greater breakthroughs in this field.

Cohort study is one of the important research methods in analytical epidemiology because of its clear time sequence relationship, which is better than other observational studies in demonstrating causal association. However, screening diagnosis or other methods are often used to exclude the individuals with outcome events during the enrollment process of the subjects in cohort studies. The accuracy of screening diagnosis and the effectiveness of exclusion will affect the accuracy of the baseline status assessment of the subjects included in the study, which may lead to the causal time sequence reversal of exposure-outcome in the estimation of causal effect. Landmark analysis can be used to control reverse causality by excluding subjects with potentially unknown expose-outcome timing. In this paper, we describe the basic principles and analytical steps of landmark analysis, and use data from the Chinese Longitudinal Healthy Longevity Survey to explore the relationship between physical activity and frailty, and introduce the specific application of landmark analysis for the purpose of facilitating its application and inferring causal effects more accurately in cohort studies.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

ObjectiveTo compare the efficacy and safety of acupuncture combined with auricular acupoints patches and nicotine transdermal patch in treating moderate to severe nicotine dependence. MethodsIn a rando-mized controlled trial， 64 quit smoking voluntary subjects with moderate to severe nicotine dependence were randomly divided at a ratio of 1∶1 into a treatment group and a control group， with 32 cases in each group. The treatment group was given acupuncture combined with auricular acupoints patches， twice weekly， four weeks as a course for two courses. The control group was given nicotine transdermal patch， one patch per day for 24 hours， 8 weeks. The cure rate was assessed after treatment and at follow-up （the 16th week after treatment）.The daily smoking volume， exhaled carbon monoxide （CO） value， Nicotine Dependence Scale （FTND）， Minnesota Nicotine Withdrawal Symptoms Scale （MNWS）， and Pittsburgh Sleepiness Index Inventory （PSQI） were evaluated before and after treatment and at follow-up， and adverse effects were recorded. ResultsIn terms of the cure rate， there were both six cured cases （20%） after treatment and at follow-up in the treatment group， while in the control group， seven （23.3%） and five （16.7%） patients were cured after treatment and at follow-up， respectively， with no statistically significant differences between the two groups both after treatment and at follow-up （P＞0.05）. The daily smoking volume and exhaled CO value significantly decreased after treatment and at follow-up in both groups （P＜0.05）， but were not significantly different between the groups after treatment and at follow-up （P＞0.05）. After treatment and at follow-up， FTND， MNWS， and PSQI scores were significantly reduced in both groups compared with those before treatment （P＜0.05）. There was no statistically significant difference in the FTND scale scores between the two groups after treatment and at follow-up （P＞0.05）， while the MNWS and PSQI scale scores were lower in the treatment group than in the control group （P＜0.05）. ConclusionAcupuncture combined with auricular acupoint patches for moderate to severe nicotine dependence has comparable effect with the first-line drug nicotine patch in terms of increasing the cure rate and decreasing the degree of nicotine dependence， and is superior to nicotine patch in terms of relieving withdrawal symptoms and improving sleep， with stable long-term effect.

Objective:To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis.Methods:The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ，included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed.Results:（1） PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups ( P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different ( P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups ( P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC （type Ⅱ） than those of low-grade （type Ⅰ） and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences ( P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant ( P<0.05). Conclusions:The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.

Objective: To explore the status of adolescents’ health risk behaviors, relationship between cognitive ability and health risk behaviors, and provide an empirical reference for reducing the occurrence and early prevention of health risk behaviors among adolescents. Methods: Samples were extracted by hierarchical, multi-stage, probability and scale proportional (PPS) methods. There were 112 schools randomly selected from 28 county-level regions(county, district, city), and 19 487 students were investigated by baseline survey, a follow-up study was conducted among 8 636 students during 2014-2015. Descriptive statistical methods of using 2 test and t test, and logistic multivariate regression analysis were used to analyze the relationship between cognitive abilities and healthy risk behaviors. Results: The reported rate of a healthy risk behavior was 20.77%, and the incidence of more than one type of health risk behavior was 16.03%. The student’s cognitive ability standardized score was(0.33±0.82). The average score of cognitive ability of adolescents with healthy risk behavior was 0.14, which was lower than the average score of cognitive ability of adolescents without healthy risk behaviors(0.43). Boys, having rural household registeration, non-residential schools, and parents with low education levels adolescents were more likely to be involved in health behavior risks. There was a significant correlation between adolescent cognitive ability and healthy risk behavior(OR=0.67, P<0.01). Conclusion The current status of adolescent health risk behaviors is worrying. The cognitive ability has a significant impact on health risk behaviors. It is recommended to use the cognitive ability of adolescents as a starting point to prevent and reduce the occurrence of adolescent health risk behaviors.

Objective To screen protein disulfide isomerase(PDI)inhibitors from zinc- and selenium-rich green tea and to examine the effect of PDI inhibitors on platelet aggregation. Methods Protein structure file of PDI(PDB ID:4EKZ)was downloaded from protein data bank and the current known 20 compounds in green tea were used to establish a small chemical library. The effects of 6 hit compounds by virtual screening on enzymatic activity of PDI were validated. The antiplatelet activities of the effective compounds tested on PDI enzymatic activi ty were further evaluated. Results 2 of 6 hit compounds by virtual screening ,ECG and EGCG displayed inhibitory effect on enzymatic activity of PDI. In addition ,both compounds showed the potential inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in vitro. Conclusion The effect of blood-activating and stasis-dissolving regulation of green tea is associated with its inhibitory effect on PDI. ECG and EGCG are major active components.

Objective To explore the diagnostic value of contrast enhanced ultrasound (CEUS),elastography and their combined use in diagnosing non-mass-like lesions on breast.Methods From November 2015 to January 2017,79 nodules diagnosed by conventional ultrasound were prospectively enrolled and examined by CEUS and elastography before surgery.Multivariate logistic regression models were established for CEUS and CEUS combined with elastography to diagnose breast malignancy.The diagnostic performances of CEUS,elastography and their combined use were evaluated with the receiver operating characteristic (ROC) curve.Results The CEUS features significantly predicting malignancy were hyperenhancement,heterogeneous enhancement,visualization of penetrating vessels (P ＜ 0.01).Furthermore,the multivariate logistic regression for CEUS combined with elastography showed that heterogeneous enhancement,visualization of penetrating vessels and elasticity score were the independent predictors of breast malignancy.The area under the ROC curve of CEUS combined with elastography was (0.915 ± 0.223),which was higher than that of CEUS and elatography (0.851 ±0.029,0.790 ±0.038,P ＜0.05).Moreover,the sensitivity,and accuracy of CEUS combined with elastography were 89.1％,and 86.1％,respectively.The omission diagnostic rate of CEUS combined with elastography (8.9％) was reduced.The diagnostic accuracy of CEUS combined with elastography was significantly higher than that of CEUS and elastography.Conclusions The diagnostic value of CEUS combined with elastography was remarkably significant in the differential diagnosis of non-mass-like lesions on breast.

Objective To assess the diagnostic value of contrast enhanced ultrasound (CEUS),elastography and their combined use in diagnosing thyroid nodules of thyroid imaging reporting and data system (TI-RADS) 4. Methods From November 2011 to August 2016, 159 TI-RADS 4 nodules diagnosed by conventional ultrasound were prospectively enrolled and examined by CEUS and elastography before surgery. Multivariate logistic regression models were established for CEUS and CEUS combined with elastography to diagnose thyroid malignancy. The diagnostic performances of CEUS, elastography and their combined use were evaluated with the receiver operating characteristic (ROC) curve. The sensitivity,specificity, accuracy, positive predictive value, negative predictive value and omission diagnostic rate of CEUS, elastography and their combined use were compared by Chi-square test. Results The CEUS features significantly predicting malignancy were heterogeneous enhancement, hypoenhancement, without or incomplete ring-enhancement and later time to peak than the surrounding parenchyma (χ2=24.378, 69.194,29.434 and 7.375, all P < 0.01). Furthermore, the multivariate logistic regression for CEUS combined with elastography showed that heterogeneous enhancement, ring enhancement and elasticity score were the independent predictors of thyroid malignancy. The area under the ROC curve of CEUS combined with elastography was (0.921±0.023) which was higher than that of CEUS and elatography (0.88±0.029 and 0.80±0.038, respectively; both P < 0.05). Moreover, the sensitivity, accuracy and negative predictive value of CEUS combined with elastography were 92.1%, 86.2% and 84.6%, respectively. The omission diagnostic rate of CEUS combined with elastography (7.9%) was reduced. And the diagnostic accuracy of CEUS combined with elastography was significantly higher than that of CEUS and elastography (P < 0.05). While the diagnostic accuracy of CEUS was close to the elastography, the difference was not statistically significant (P > 0.05). Conclusion The diagnostic value of CEUS combined with elastography was remarkably significant in the differential diagnosis of TI-RADS 4 nodules.