Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective:To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs).Methods:A total of 28 unrelated CFDs patients admitted to Wenzhou People′s Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg: C), fibrinogen antigen (Fg: Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted by PolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People′s Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment.Results:The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. ①Clinical data: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg: C. ②Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c. 902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c. 569 A>G (28.6%, 8/28). ③Biological informatics analysis: the Aα c. 180+ 1G>T mutation was predicted to be highly deleterious. And the Aα c. 104G>A, Bβ c. 425T>G, Bβ c. 586C>T, and γ c. 902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ④ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c. 104G>A, Aα c. 180+ 1G>T, Bβ c. 425T>G, Bβ c.569A>G, Bβ c. 586C>T, Bβ c. 643G>A, γ c. 901C>T, γ c. 902G>A, γ c. 1001A>C) were classified as pathogenic, while one variation (γ c. 908C>G) was classified as likely pathogenic. Conclusion:In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

OBJECTIVE: To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs). METHODS: A total of 28 unrelated CFDs patients admitted to Wenzhou People's Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg:C), fibrinogen antigen (Fg:Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted byPolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People's Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment. RESULTS: The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. CLINICAL DATA: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg:C. Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c.902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c.569 A>G (28.6%, 8/28). Biological informatics analysis: the Aα c.180+1G>T mutation was predicted to be highly deleterious. And the Aα c.104G>A, Bβ c.425T>G, Bβ c.586C>T, and γ c.902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c.104G>A, Aα c.180+1G>T, Bβ c.425T>G, Bβ c.569A>G, Bβ c.586C>T, Bβ c.643G>A, γ c.901C>T, γ c.902G>A, γ c.1001A>C) were classified as pathogenic, while one variation (γ c.908C>G) was classified as likely pathogenic. CONCLUSION In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.
Humans ; Female ; Male ; Afibrinogenemia/congenital* ; Fibrinogen/metabolism* ; Mutation ; Genotype ; Adult ; Child ; Adolescent ; Child, Preschool ; Infant

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Objective:To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs).Methods:A total of 28 unrelated CFDs patients admitted to Wenzhou People′s Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg: C), fibrinogen antigen (Fg: Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted by PolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People′s Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment.Results:The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. ①Clinical data: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg: C. ②Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c. 902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c. 569 A>G (28.6%, 8/28). ③Biological informatics analysis: the Aα c. 180+ 1G>T mutation was predicted to be highly deleterious. And the Aα c. 104G>A, Bβ c. 425T>G, Bβ c. 586C>T, and γ c. 902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ④ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c. 104G>A, Aα c. 180+ 1G>T, Bβ c. 425T>G, Bβ c.569A>G, Bβ c. 586C>T, Bβ c. 643G>A, γ c. 901C>T, γ c. 902G>A, γ c. 1001A>C) were classified as pathogenic, while one variation (γ c. 908C>G) was classified as likely pathogenic. Conclusion:In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

Objective:To quantitatively analyze infection prevention and control policy texts related to medical alliance, aiming to provide reference for further policy improvement.Methods:with the " medical alliance" and " infection prevention and control" as keywords, relevant policy documents issued from January 2015 to March 2023 were searched on the Chinese government website, the official website of the National Health Commission, and the Peking University law database. Content analysis method was used to quantitatively analyze policy texts from two dimensions: policy tools (supply oriented, environmental oriented, demand oriented) and systems theory (management, service, human resources, and financing systems as internal subsystems, while political, economic, social, and technological systems as external subsystems).Results:A total of 91 infection prevention and control policy documents related to medical alliance were included, and 199 codes were obtained. There were 114, 78, and 7 codes for environmental oriented, supply oriented, and demand oriented policy tools, respectively; among the demand oriented tools, there were only 1 code for government purchases, 1 code for price subsidies, and 5 codes for demonstration project sub tools, respectively. The internal subsystem had a total of 119 codes, with only 2 codes related to the fundraising system; and the external subsystem had a total of 80 codes, with the least 10 codes related to the technical system.Conclusions:The structure of infection prevention and control policy tools in China′s medical alliance needed to be optimized, and the application of demand oriented policy tools was insufficient. It is necessary to strengthen the use of pull tools such as government purchases, price subsidies, and demonstration projects. At the same time, it is necessary to improve the construction of internal and external systems, especially in terms of fundraising and technology systems, to enhance the overall effectiveness of the medical alliance′s infection prevention and control system.

The purpose of this study was to investigate the damage mechanism of pathogenic E.coli on mouse brain microvascular endothelial cells(BMEC cells)and mouse alveolar macrophages(MH-S cells),as well as the lung and brain of healthy mice.In this study,BMEC cells and MH-S cells were infected with pathogenic E.coli strains,and cell morphological changes were observed.Plate counting method was used to detect the adhesion and invasion ability of the strains to cells and the number of bacteria in the lungs and brains of mice.RT-qPCR was used to detect the ex-pression of TNF-α,IL-1β and IL-6 genes in cells and mouse organs at different time periods.West-ern blot was used to detect the expression of p-NF-κB,p-JAK2 and p-STAT3 proteins related to inflammation in cells and mouse organs after infection.The results showed that the cell culture medium of the infection group was turbid,the cell vision became dark and blurred,some cells shrank and died,and more fragments were produced.The adhesion rate and invasion rate of BMEC cells at 3 h were significantly lower than those at 6 h(P＜0.050),and the adhesion rate and inva-sion rate of MH-S cells at 3 h were significantly higher than those at 6 h(P＜0.010).Infected mice had a large area of swelling and bleeding in the brain,and the lungs had different degrees of swell-ing and bleeding.The bacterial load in the brain and lung was the highest at 12 h.Compared with the control group,the mRNA expression levels of IL-1β,IL-6 and TNF-α in the infection group were significantly increased at 3 h and 6 h(P＜0.050),and the mRNA expression levels of inflam-matory factors in BMEC cells and MH-S cells were the highest at 6 and 3 h,respectively.The mR-NA expression of inflammatory factors in the brain and lung of infected mice showed a trend of in-creasing first and then decreasing with time,with the highest expression at 12 h after infection.The expression levels of p-NF-κB protein in BMEC cells,MH-S cells,lung and brain tissues of mice in the infection group were significantly higher than those in the control group(P＜0.001),and the expression levels of p-JAK2 protein and p-STAT3 protein were significantly lower than those in the control group(P＜0.050).The above results showed that pathogenic E.coli could adhere and invade BMEC cells and MH-S cells,colonize in lung and brain tissues of mice,promote the expres-sion of NF-κB protein in cells and tissues,inhibit the expression of JAK2 protein and STAT3 pro-tein,and then stimulate cells and tissues to produce inflammatory response.