Objective To study the safety of amlodipine post-marketing and to mine the potential adverse drug event(ADE)signals,and to construct an intelligent query platform for ADE signals that can be popularized and applied to a variety of drugs.Methods The data from the first quarter of 2004 to the fourth quarter of 2024 were retrieved from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database.A variety of disproportionality methods were used,including the reporting odds ratio(ROR)method,the United Kingdom Medicines and Healthcare products Regulatory Agency(MHRA)comprehensive standard method,Bayesian confidence propagation neural network(BCPNN)method,and the multi-item Gamma-Poisson shrinker(MGPS)method,to mine the signals of ADEs related to amlodipine.At the same time,a general query platform for mining ADE signals was developed based on the DeepSeek AI model to achieve the monitoring and analysis of the safety of various drugs.Results A total of 51,166 ADE reports were obtained,in which amlodipine was the primary suspected drug.Through the combined screening of the four algorithms,multiple potential ADE signals which had not been mentioned in the existing package inserts were found,including diseases of the ear and labyrinth(such as sensorineural hearing loss),diseases of the respiratory system,thorax and mediastinum(such as non-cardiogenic pulmonary edema),mental disorders(such as completed suicide),etc.The constructed digital intelligent platform had achieved the automated processing and monitoring of ADE data,providing a rapid access for clinicians and regulatory authorities to obtain drug safety information.Conclusion This study reveals potential safety risks associated with the use of amlodipine through real-world data mining.A risk assessment of patients' medication should be carried out before clinical use.In addition to paying attention to known ADEs,newly discovered potential risk signals should also be closely monitored.The construction of the digital intelligent platform provides an efficient tool for pharmacovigilance work.It can be popularized and applied to the safety monitoring of a variety of drugs,which is of great significance for improving the level of pharmacovigilance and the safety of medication.

Objective:To translate the Vascular Quality of Life Questionnaire-6 (VQ6) into a Chinese version and to test its reliability and validity in patients with peripheral arterial disease.Methods:The English version of VQ6 scale was sinicized following the Brislin translation guidelines, and the Delphi consultation was used for cultural debugging to form the Chinese version of the VQ6. Convenience sampling was used to select 146 patients with peripheral arterial disease who attended the Department of Interventional and Vascular Surgery and the Department of Endocrinology of Affiliated Hospital of Nantong University from May to June 2024 for the survey. Data were analyzed using SPSS 26.0 and Amos 26.0. Correlation analysis and critical ratio method were used for item analysis and content validity index was used to evaluate content validity. The Chinese version of the Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (PROMIS-29 Profile v2.1) was selected as a validity scale to evaluate the criterion-related validity. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the scale, and transgender test was used for measurement equivalence. Reliability of the scale was evaluated with the Cronbach's α coefficient and retest reliability index.Results:The Chinese version of the VQ6 scale had six items. The scale-level content validity index was 0.972, and the item-level content validity index ranged from 0.833 to 1.000. One common factor was extracted with a cumulative variance contribution of 83.526%. Criterion-related validity showed that the correlation coefficient between the Chinese version of the VQ6 and the PROMIS-29 Profile v2.1 was 0.688 ( P<0.01) . The scale essentially satisfied Δ RMSEA < 0.015 and Δ CFI < 0.01 in the transgender equivalence test. The Cronbach's α coefficient for the scale was 0.968 and the retest reliability was 0.978. Conclusions:The Chinese version of the VQ6 has good reliability and validity and is suitable as an assessment tool for quality of life in patients with peripheral arterial disease in our cultural context.

Objective To study the safety of amlodipine post-marketing and to mine the potential adverse drug event(ADE)signals,and to construct an intelligent query platform for ADE signals that can be popularized and applied to a variety of drugs.Methods The data from the first quarter of 2004 to the fourth quarter of 2024 were retrieved from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database.A variety of disproportionality methods were used,including the reporting odds ratio(ROR)method,the United Kingdom Medicines and Healthcare products Regulatory Agency(MHRA)comprehensive standard method,Bayesian confidence propagation neural network(BCPNN)method,and the multi-item Gamma-Poisson shrinker(MGPS)method,to mine the signals of ADEs related to amlodipine.At the same time,a general query platform for mining ADE signals was developed based on the DeepSeek AI model to achieve the monitoring and analysis of the safety of various drugs.Results A total of 51,166 ADE reports were obtained,in which amlodipine was the primary suspected drug.Through the combined screening of the four algorithms,multiple potential ADE signals which had not been mentioned in the existing package inserts were found,including diseases of the ear and labyrinth(such as sensorineural hearing loss),diseases of the respiratory system,thorax and mediastinum(such as non-cardiogenic pulmonary edema),mental disorders(such as completed suicide),etc.The constructed digital intelligent platform had achieved the automated processing and monitoring of ADE data,providing a rapid access for clinicians and regulatory authorities to obtain drug safety information.Conclusion This study reveals potential safety risks associated with the use of amlodipine through real-world data mining.A risk assessment of patients' medication should be carried out before clinical use.In addition to paying attention to known ADEs,newly discovered potential risk signals should also be closely monitored.The construction of the digital intelligent platform provides an efficient tool for pharmacovigilance work.It can be popularized and applied to the safety monitoring of a variety of drugs,which is of great significance for improving the level of pharmacovigilance and the safety of medication.

Objective:To translate the Vascular Quality of Life Questionnaire-6 (VQ6) into a Chinese version and to test its reliability and validity in patients with peripheral arterial disease.Methods:The English version of VQ6 scale was sinicized following the Brislin translation guidelines, and the Delphi consultation was used for cultural debugging to form the Chinese version of the VQ6. Convenience sampling was used to select 146 patients with peripheral arterial disease who attended the Department of Interventional and Vascular Surgery and the Department of Endocrinology of Affiliated Hospital of Nantong University from May to June 2024 for the survey. Data were analyzed using SPSS 26.0 and Amos 26.0. Correlation analysis and critical ratio method were used for item analysis and content validity index was used to evaluate content validity. The Chinese version of the Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (PROMIS-29 Profile v2.1) was selected as a validity scale to evaluate the criterion-related validity. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the scale, and transgender test was used for measurement equivalence. Reliability of the scale was evaluated with the Cronbach's α coefficient and retest reliability index.Results:The Chinese version of the VQ6 scale had six items. The scale-level content validity index was 0.972, and the item-level content validity index ranged from 0.833 to 1.000. One common factor was extracted with a cumulative variance contribution of 83.526%. Criterion-related validity showed that the correlation coefficient between the Chinese version of the VQ6 and the PROMIS-29 Profile v2.1 was 0.688 ( P<0.01) . The scale essentially satisfied Δ RMSEA < 0.015 and Δ CFI < 0.01 in the transgender equivalence test. The Cronbach's α coefficient for the scale was 0.968 and the retest reliability was 0.978. Conclusions:The Chinese version of the VQ6 has good reliability and validity and is suitable as an assessment tool for quality of life in patients with peripheral arterial disease in our cultural context.

Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10
Aneurysm, Dissecting/genetics* ; Case-Control Studies ; Cluster Analysis ; Cohort Studies ; Collagen Type III/genetics* ; Computational Biology ; Genetic Predisposition to Disease ; Humans

Objective: To explore the expression of FAT1 in esophageal squamous cell carcinoma (ESCC) tissues, and its effect on cell proliferation. Methods: The expression levels of FAT1 protein in human ESCC tissues and matched adjacent normal tissues were determined by immunohistochemistry (IHC). Lentivirus based knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assays was performed to examine the effect of FAT1 on the proliferation of these ESCC cells. Colony formation assay was used to detect the colony formation ability. Flow cytometry was performed to analyze the cell cycle and apoptosis. The expression levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR) and Western blot. Results: The relative expression of FAT1 in ESCC tissues was 66.97±21.53, significantly lower than 78.13±16.76 of adjacent normal tissues(P<0.05). Knockdown of FAT1 promoted cell proliferation and colony formation. In YSE2 cell, the division time in negative control (NC) group was (1 570±51) min, significantly longer than (1 356±31) min in shFAT1 group. In Colo680N cell, division time in NC group was (1 532±53) min, significantly longer than (1 290±30) min in shFAT1 group (P<0.05). Knockdown of FAT1 promoted G1-to S-phase transition and resulted in the upregulation of CDK4/CDK6/CCND1. Conclusion FAT1 inhibits the proliferation and G1-to S-phase transition of ESCC cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.

Objective To explore the expression of FAT1 in esophageal squamous cell carcinoma ( ESCC) tissues, and its effect on cell proliferation. Methods The expression levels of FAT1 protein in human ESCC tissues and matched adjacent normal tissues were determined by immunohistochemistry ( IHC) . Lentivirus based knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3?( 4,5?dimethyl?2?thiazolyl)?2,5?diphenyl?2H tetrazolium bromide ( MTT) assays was performed to examine the effect of FAT1 on the proliferation of these ESCC cells. Colony formation assay was used to detect the colony formation ability. Flow cytometry was performed to analyze the cell cycle and apoptosis. The expression levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by real?time quantitative reverse transcription polymerase chain reaction( qRT?PCR) and Western blot. Results The relative expression of FAT1 in ESCC tissues was 66. 97 ± 21. 53, significantly lower than 78. 13 ± 16. 76 of adjacent normal tissues ( P<0.05) . Knockdown of FAT1 promoted cell proliferation and colony formation. In YSE2 cell, the division time in negative control (NC) group was (1570±51) min, significantly longer than (1356±31) min in shFAT1 group. In Colo680N cell, division time in NC group was (1532±53) min, significantly longer than (1290±30) min in shFAT1 group (P<0.05). Knockdown of FAT1 promoted G1?to S?phase transition and resulted in the upregulation of CDK4/CDK6/CCND1. Conclusion FAT1 inhibits the proliferation and G1?to S?phase transition of ESCC cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.

Objective To explore the expression of FAT1 in esophageal squamous cell carcinoma ( ESCC) tissues, and its effect on cell proliferation. Methods The expression levels of FAT1 protein in human ESCC tissues and matched adjacent normal tissues were determined by immunohistochemistry ( IHC) . Lentivirus based knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3?( 4,5?dimethyl?2?thiazolyl)?2,5?diphenyl?2H tetrazolium bromide ( MTT) assays was performed to examine the effect of FAT1 on the proliferation of these ESCC cells. Colony formation assay was used to detect the colony formation ability. Flow cytometry was performed to analyze the cell cycle and apoptosis. The expression levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by real?time quantitative reverse transcription polymerase chain reaction( qRT?PCR) and Western blot. Results The relative expression of FAT1 in ESCC tissues was 66. 97 ± 21. 53, significantly lower than 78. 13 ± 16. 76 of adjacent normal tissues ( P<0.05) . Knockdown of FAT1 promoted cell proliferation and colony formation. In YSE2 cell, the division time in negative control (NC) group was (1570±51) min, significantly longer than (1356±31) min in shFAT1 group. In Colo680N cell, division time in NC group was (1532±53) min, significantly longer than (1290±30) min in shFAT1 group (P<0.05). Knockdown of FAT1 promoted G1?to S?phase transition and resulted in the upregulation of CDK4/CDK6/CCND1. Conclusion FAT1 inhibits the proliferation and G1?to S?phase transition of ESCC cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.