Objective To summarize the current status of outcome indicators in randomized controlled trials of TCM intervention in pediatric myocarditis,to explore the existing problems,and to provide a reference for the construction of a core set of indicators for the treatment of pediatric myocarditis with TCM.Methods Randomized controlled trial literature on the treatment of pediatric myocarditis with TCM was retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Embase,Cochrane Library and Web of Science from the establishment of the databases to 16th,Nov.2024.The basic characteristics,diagnostic criteria,TCM evidence,interventions and outcome indicators of the studies were extracted.The risk of bias was assessed for the selected studies using the Cochrane Collaboration's risk of bias tool(RoB 2.0),and the outcome indicators were statistically analyzed using Excel 2019.Results Finally,totally of 250 articles were included in the literature.The outcome indicators were counted to obtain 187 outcome indicators with a cumulative total of 1 540 occurrences,which were categorized into six indicator domains:symptoms and signs,physicochemical testing,TCM symptoms/signs,clinical efficacy evaluation,safety evaluation and quality of life evaluation;among them,the physicochemical testing indicators(112 types,926 times)had the highest frequency of occurrences,followed by the clinical efficacy evaluation(13 types.340 times),and safety evaluation(24 types,193 times).Conclusion The overall quality of randomized controlled trials of TCM treatment of pediatric myocarditis is low,and there are problems with primary and secondary differentiation of outcome indicators and lack of TCM characteristics.There is an urgent need to improve the core set of endpoint indicators that highlight the characteristics of TCM in order to improve the quality of clinical research.

Objective To summarize the current status of outcome indicators in randomized controlled trials of TCM intervention in pediatric myocarditis,to explore the existing problems,and to provide a reference for the construction of a core set of indicators for the treatment of pediatric myocarditis with TCM.Methods Randomized controlled trial literature on the treatment of pediatric myocarditis with TCM was retrieved from CNKI,Wanfang Data,VIP,SinoMed,PubMed,Embase,Cochrane Library and Web of Science from the establishment of the databases to 16th,Nov.2024.The basic characteristics,diagnostic criteria,TCM evidence,interventions and outcome indicators of the studies were extracted.The risk of bias was assessed for the selected studies using the Cochrane Collaboration's risk of bias tool(RoB 2.0),and the outcome indicators were statistically analyzed using Excel 2019.Results Finally,totally of 250 articles were included in the literature.The outcome indicators were counted to obtain 187 outcome indicators with a cumulative total of 1 540 occurrences,which were categorized into six indicator domains:symptoms and signs,physicochemical testing,TCM symptoms/signs,clinical efficacy evaluation,safety evaluation and quality of life evaluation;among them,the physicochemical testing indicators(112 types,926 times)had the highest frequency of occurrences,followed by the clinical efficacy evaluation(13 types.340 times),and safety evaluation(24 types,193 times).Conclusion The overall quality of randomized controlled trials of TCM treatment of pediatric myocarditis is low,and there are problems with primary and secondary differentiation of outcome indicators and lack of TCM characteristics.There is an urgent need to improve the core set of endpoint indicators that highlight the characteristics of TCM in order to improve the quality of clinical research.

Background:The incidence of colorectal cancer(CRC)remains high in China.ITGBL1,an intergrin-like molecule,may play a significant role in the tumorigenesis and progression of CRC.Aims:To explore the expression of ITGBL1 in CRC tissues,and its clinical significance and effect on the biological function of CRC cells.Methods:Fifty-five paraffin embedding cancerous and paracancerous tissues from CRC patients undergoing surgical treatment were collected.Protein expression of ITGBL1 was detected by immunohistochemistry.The relationship between ITGBL1 expression and the clinicopathological characteristics of the CRC patients was analyzed.Furthermore,the sh-ITGBL1 lentiviral system was used to construct ITGBL1 knockdown stably-transformed HCT116 and RKO cells,then the ITGBL1 protein expression was detected by Western blotting.Effects of ITGBL1 knockdown on the proliferation of CRC cells were analyzed by CCK-8 assay and colony formation assay.Results:ITGBL1 was highly expressed in CRC tissues and cells.Expression of ITGBL1 was positively correlated with the infiltration depth,lymph node metastasis and the clinical stage of CRC(all P＜0.05),whereas no correlations were found between ITGBL expression and the gender,age,tumor size,tumor differentiation,and distant metastasis of CRC patients.Compared with the control group(sh-NC),ITGBL1 expression was significantly decreased in ITGBL1 knockdown(sh-ITGBL1)HCT116 and RKO cells,and the cell proliferation was significantly inhibited(all P＜0.05).Conclusions:Highly expressed ITGBL1 may be associated with the occurrence and development of CRC.ITGBL1 knockdown exerts a significant inhibitory effect on the proliferation of CRC cells.Therefore,ITGBL1 might be a potential biomarker,which is expected to be a new target for diagnosis and treatment of CRC.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

Objective To compare the reflux characteristics between reflux esophagitis (RE) patients with Los Angeles (LA) classification grade A and grades B/C based on esophageal pH-impedance monitoring results. Methods A total of 74 RE patients at Zhongshan Hospital (Xiamen Branch), Fudan University from June 2021 to June 2024 were enrolled, and were divided into the LA-A group (n＝46) and the LA-B/C group (n＝28) based on the endoscopic diagnosis results. The general clinical data, symptom questionnaire score, and esophageal 24-hour pH-impedance monitoring results were compared between the two groups. Results There were no statistically significant differences in demographic data and the response rate of acid suppression therapy between the two groups. 24-hour esophageal pH-impedance monitoring results showed that there were no statistically significant differences in upright, supine, and total reflux indices, including reflux episodes, acid exposure time (AET), AET percentage (AET%), long acid reflux episodes, longest reflux duration, and total DeMeester score between the two groups. There were no statistically significant differences in distal reflux episodes, proximal reflux episodes, and high reflux (acid, weak acid, and non-acidic reflux) episodes, mean nocturnal baseline impedance (MNBI) between the two groups. The rates of pathological reflux (AET%≥6%) in LA-A group and LA-B/C group were 67.4% and 71.4%, respectively; there were no statistically significant differences in the ratio of AET% composition and the count of impedance reflux exceeding 80 during 24 h between the two groups. Conclusions LA-A grade RE based on the endoscopic diagnosis facilitates the identification of gastroesophageal reflux disease in the Chinese population

Background:The incidence of colorectal cancer(CRC)remains high in China.ITGBL1,an intergrin-like molecule,may play a significant role in the tumorigenesis and progression of CRC.Aims:To explore the expression of ITGBL1 in CRC tissues,and its clinical significance and effect on the biological function of CRC cells.Methods:Fifty-five paraffin embedding cancerous and paracancerous tissues from CRC patients undergoing surgical treatment were collected.Protein expression of ITGBL1 was detected by immunohistochemistry.The relationship between ITGBL1 expression and the clinicopathological characteristics of the CRC patients was analyzed.Furthermore,the sh-ITGBL1 lentiviral system was used to construct ITGBL1 knockdown stably-transformed HCT116 and RKO cells,then the ITGBL1 protein expression was detected by Western blotting.Effects of ITGBL1 knockdown on the proliferation of CRC cells were analyzed by CCK-8 assay and colony formation assay.Results:ITGBL1 was highly expressed in CRC tissues and cells.Expression of ITGBL1 was positively correlated with the infiltration depth,lymph node metastasis and the clinical stage of CRC(all P＜0.05),whereas no correlations were found between ITGBL expression and the gender,age,tumor size,tumor differentiation,and distant metastasis of CRC patients.Compared with the control group(sh-NC),ITGBL1 expression was significantly decreased in ITGBL1 knockdown(sh-ITGBL1)HCT116 and RKO cells,and the cell proliferation was significantly inhibited(all P＜0.05).Conclusions:Highly expressed ITGBL1 may be associated with the occurrence and development of CRC.ITGBL1 knockdown exerts a significant inhibitory effect on the proliferation of CRC cells.Therefore,ITGBL1 might be a potential biomarker,which is expected to be a new target for diagnosis and treatment of CRC.

Objective: To provide ideas for the modernization of pulse diagnosis in traditional Chinese medicine (TCM) by comparing and analyzing the current status and trends of modern research on pulse diagnosis in China and abroad, using bibliometric and visualization software. Methods: Modern research literature on pulse diagnosis was searched in China National Knowledge Infrastructure (CNKI) database from the foundation to May 31, 2023, and in Science Citation Index Expanded (SCIE) from January 1, 2003, to May 31, 2023. After further screening, Microsoft Excel 2019 was used for statistical analysis of publication volume, and CiteSpace (6.1.R6) and VOSviewer (1.6.20) softwares were employed for visual analysis of journals, countries/regions, authors, institutions, keywords, etc. Results: This study included a total of 764 articles in Chinese and 1 459 articles in English. The publication trend of pulse diagnosis research in SCIE database showed an overall fluctuating upward trend, while it exhibited a fluctuating downward trend after 2007 in CNKI database. The volume of English research literature has consistently exceeded that of Chinese literature since 2009. Publications on pulse diagnosis research involved 74 countries/regions. The related journals covered various disciplinary fields, including mathematics, physics, chemistry, and computer science. The most prolific author in CNKI database was WANG Yiqin (Shanghai University of Traditional Chinese Medicine), while the highest number of publications was attributed to ZHANG David (The Hong Kong Polytechnic University) in SCIE database. High-volume institutions in pulse diagnosis research in China and abroad were predominantly TCM research institutions. However, comprehensive universities and other research institutions also made noteworthy contributions. In recent years, hot topics in the modernization of pulse diagnosis research in China included pulse waves, sensors, and artificial intelligence. Foreign research focused on pulse diagnosis systems, sensors, pulse feature extraction, pulse signal analysis, pulse detection, and efficiency of use. Conclusion Chinese scholars have shown notable participation and emphasis in the modernization research of pulse diagnosis, involving a wide range of disciplinary fields and indicating a characteristic of multidisciplinary cross-fusion development. The hotspots andtrends in the modernization of pulse diagnosis research primarily concentrate on the study of pulse condition and signal acquisition, the integration, development, and optimization of various algorithms with pulse diagnosis equipment, and the practical application research of existing objectified outcomes of pulse diagnosis.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estima-tions and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95％ confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95％ CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism ofSARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.