1.Effect of Modified Duodenal Exclusion Surgery on Glucose Metabolism in Rats with Type 2 Diabetes Mellitus
Jin YANG ; Shiya YU ; Nan LIN ; Yongchao FANG ; Hu ZHAO ; Jinwei QIU ; Hongming LIN ; Huiyan CHEN ; Yu WANG ; Weihang WU
Laboratory Animal and Comparative Medicine 2024;44(5):523-530
Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.
2.A phase Ⅱ clinical study of the efficacy and safety of antaitasvir phosphate combined with yiqibuvir for the treatment of chronic hepatitis C in adults
Lai WEI ; Hongxin PIAO ; Jinglan JIN ; Shufen YUAN ; Xuan AN ; Jia SHANG ; Wenhua ZHANG ; Jiabao CHANG ; Tong SUN ; Yujuan GUAN ; Bo NING ; Jing ZHU ; Wentao GUO ; Qingwei HE ; Lin LUO ; Yulei ZHUANG ; Hongming XIE ; Yingjun ZHANG
Chinese Journal of Hepatology 2024;32(7):637-642
Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA
3.CT coronary perivascular fat attenuation combined with machine learning algorithms for diagnosis of myocardial ischemia in coronary heart disease
Yige LU ; Wei HE ; Hongyan LIN ; Furong HE ; Hanbo ZHANG ; Yao TAN ; Hongming ZHU
Chinese Journal of Arteriosclerosis 2024;32(6):514-520
Aim To explore the feasibility of using machine learning algorithms combined with coronary computed tomography(CT)derived perivascular fat attenuation index(FAI)and plaque information to evaluate myocardial ischemia in stable coronary heart disease patients.Methods A retrospective analysis was conducted on the clinical and imaging data of patients who underwent preoperative coronary CT angiography(CCTA),invasive coronary angiography(ICA),and flow reserve fraction(FFR)measurements at Zhongshan Hospital Affiliated to Fudan University from April 2019 to October 2021.206 patients with stable coronary heart disease were selected.The semi-automatic plaque analysis software was used for quantification of plaque and lumen parameters and perivascular FAI measurement,with man-ual delineation of a 40 mm segment of the coronary artery starting 10 mm from the ostium for perivascular FAI measure-ment.Differences in plaque characteristics,perivascular FAI,and coronary perivascular FAI between stable coronary heart disease patients with FFR≤0.8 and FFR>0.8 were compared.The diagnostic performance of combining perivascu-lar FAI,coronary perivascular FAI,and plaque features using machine learning algorithms for myocardial ischemia in stable coronary heart disease patients was evaluated through ROC curves.Results 206 stable coronary heart disease patients were divided into FFR≤0.8 group(50 cases)and FFR>0.8 group(156 cases).The mean periplaque FAI of patients with FFR≤0.8 was-69.28±5.65 HU,significantly higher than that of patients with FFR>0.8 at-80.10±7.75 HU(P<0.001).Further analysis was conducted using machine learning models,including XGBoost,random forest,and Logistic regression models,all of which had an accuracy rate of over 0.8 in diagnosing myocardial ischemia.Among them,the XGBoost model performed the best with an accuracy of 0.903,an F1 value of 0.774,and an AUC of 0.931,in-dicating its high effectiveness in diagnosing myocardial ischemia.Conclusion The combination of FAI and machine learning algorithm XGBoost model is a new method for diagnosing myocardial ischemia,which has better diagnostic value in evaluating myocardial ischemia in stable coronary heart disease patients.
4.Effect of personalized intermittent energy restriction diet on gut microbiome associated with sleep in obese patients
Jing ZHOU ; Xiaoling WU ; Zhonglin LI ; Zhi ZOU ; Yongbing SUN ; Junya HE ; Qi QIAO ; Xinbei LIN ; Yong WANG ; Shewei DOU ; Hongming LIU ; Fengshan YAN ; Yongli LI
Chinese Journal of Health Management 2023;17(9):692-697
Objective:To investigate the effects of personalized intermittent energy restriction (IER) diet on sleep related gut microbiome in obese patients.Methods:In this single-arm clinical trial, a total of 35 obese patients who visited Henan Provincial People′s Hospital from April to November 2018 were recruited as research subjects. They underwent a strict 32-day IER diet intervention, divided into 4 stages of 8 days each. Nutritional recipes were formulated and nutritious meals were provided to each obese patient with timed meals, including 55% carbohydrates, 15% protein, and 30% fat per meal. In stages 1, 2, 3, and 4, patients were provided with 2/3, 1/2, 1/3, and 1/4 of their previous calorie intake every other day, respectively, with meals at 8:00 and 16:00. During the remaining time, patients were allowed unrestricted eating at home. Physiological indicators (weight, body mass index, body fat percentage, waist circumference, hip circumference, fasting blood glucose, glycosylated hemoglobin, blood pressure, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein and Pittsburgh Sleep Quality Index (PSQI) scores were observed before and after the intervention. Gut microbiota changes were analyzed using metagenomic sequencing technology, and Spearman′s correlation analysis was used to assess the correlation between significantly different bacterial species and PSQI scores.Results:After the intervention, the body weight, body mass index, and PSQI scores of obese patients were all significantly lower than before intervention [(89.92±14.98) vs (97.53±15.67) kg, (31.94±3.95) vs (34.64±4.05) kg/m 2, (3.43±1.16) vs (5.42±2.27)], the abundance of gut microbiota was significantly higher after the intervention (all P<0.05). There were 45 significantly different bacterial species before and after the intervention, of which 6 bacterial species ( Enterobacter cloacae, Escherichia coli, Odoribacter splanchnicus, Oribacterium sinus, Streptococcus gordonii, and Streptococcus parasanguinis) showed significantly positive correlations with PSQI scores ( r=0.476, 0.475, 0.369, 0.391, 0.401, 0.423) (all P<0.05), and they were mainly enriched in the glutamate and tryptophan synthesis pathways. Conclusions:The personalized IER diet intervention can improve the sleep of obese patients while reducing weight, possibly mediated by changes in gut microbiota through the glutamate and tryptophan pathways.
5.Primary retroperitoneal soft tissue sarcoma resection combined with nephrectomy: a report 27 cases
Jiaxin LIN ; Dechang DIAO ; Weilin LIAO ; Jiahao WANG ; Xin TANG ; Wenjuan LI ; Hongming LI ; Xiaojiang YI ; Xinquan LU ; Xiaochuang FENG ; Zhaoyu CHEN
Chinese Journal of General Surgery 2023;38(12):905-908
Objective:To investigate the efficacy and safety of retroperitoneal soft tissue sarcoma resection combined with nephrectomy.Methods:The clinical data of 27 cases undergoing retroperitoneal soft tissue sarcoma resection combined with nephrectomy at the Gastrointestinal Tumor Center , Guangdong Provincial Hospital , Traditional Chinese Medicine from Jun 2017 to Aug 2022 were retrospectively analyzed for the indication of nephrectomy, postoperative progression of renal insufficiency and survival rate.Results:Twenty-six cases (96%) achieved R 0/R 1 resection and 1 case nderwent R 2 resection. Six cases underwent combined unilateral nephrectomy and 21 patients underwent combined multi-organ resection with a median number of resections of 4 (2,5). Postoperative pathology suggested that the combined resected kidney was positive for tumor infiltration in 17 cases. Five cases had Clavien-Dindo grade 3 or higher complications and no deaths occurred within 30 days after surgery. At the 90th day after surgery, 19 cases (70%) had decreased renal function ( Z=2.88, P=0.04), with a median decrease of -3.96 (-30.36, 0.31)ml·(min·1.73 m 2) -1, including 8 cases of preoperative Chronic Kidney Disease(CKD)1 stage progression (6 cases of CKD 2 stage, 2 cases of CKD 3 stage); 2 cases of CKD 2 stage progressed to CKD 3 stage; 1 case of preoperative CKD 3 stage progressed to CKD 4 stage. During the follow-up period of 3-38 months, no patient progressed to CKD 5 stage and no patient required dialysis treatment. Conclusion:Retroperitoneal soft tissue sarcoma resection combined with nephrectomy is safe and feasible while improving tumor radicality.
6.Male Infertility Responding Specifically to Traditional Chinese Medicine
Yutian ZHU ; Bin WANG ; Wei LI ; Sheng LIN ; Jingshang WANG ; Fu WANG ; Minghui KE ; Dalin SUN ; Hai WANG ; Yong ZHAO ; Hongming LIU ; Yuan TANG ; Sheng WANG ; Yong ZHU ; Haisong LI ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):223-228
In recent years,with the change in lifestyle and social environment and the increase in pressure in both life and work,male fertility has decreased significantly in China,and the incidence of male infertility has increased year by year,which has brought great challenges to andrologists. Traditional Chinese medicine (TCM) has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility,the China Association of Chinese Medicine (CACM) invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia,abnormal semen liquefaction,varicocele,immune infertility,improving success ratio of assisted reproductive technology,and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages,characteristics,disadvantages,diseases responding specifically,and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility,western medicine cannot achieve a good curative effect,while TCM,taking the holistic view as the core,specializes in improving functional diseases and can correspond to multiple targets and factors,with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists,increase mutual learning and communication between TCM and western physicians,provide patients with excellent and personalized treatment plans in clinical practice,and improve the curative effect of male infertility and fertility of males in China.
7.Feasibility of a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection for middle and low rectal cancer
Wenjuan LI ; Dechang DIAO ; Jiaxin LIN ; Jiahao WANG ; Weilin LIAO ; Xin TANG ; Jiaxin XIE ; Lin AO ; Xueyang ZHANG ; Xiaojiang YI ; Xiaochuang FENG ; Hongming LI ; Xinquan LU
Chinese Journal of Gastrointestinal Surgery 2023;26(10):968-976
Objective:To explore the feasibility and value of performing a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection (LLND) for middle and low rectal cancer.Methods:This was a retrospective review. The study cohort comprised patients who met the diagnostic criteria for rectal cancer according to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer, had a short lymph node diameter of >5 mm on the lateral side within the 15 days before surgery, were evaluated as feasible candidates for laparoscopic total mesorectal excision+LLND surgery, had been diagnosed with low or intermediate level rectal cancer, and whose tumor was less than 8 cm away from the anal verge according to pathological examination of the operative specimen. Patients with a history of other malignant tumors of the abdomen or with incomplete follow-up data were excluded. Forty-two patients with middle and low rectal cancer who had undergone lateral lymph node dissection in diagnosis and treatment center of Gastrointestinal Cancer of Guangdong Hospital of Chinese Medicine from Jan.2018 to Dec.2022 were enrolled. There were 24 men (57.1%) and 18 women (42.9%) aged 58.4±11.8 years and the median BMI was 22.5 (19.3–24.1) kg/m 2. The main point of the three-sided encapsulation procedure is to expand the external side medial to the external iliac artery and vein, narrowing the range of exterior side dissection. The anterior-medial side is designed to expand the vesical fascia to define the range of anterior-medial side extension. The internal side is fully extended to the ureterohypogastric nerve fascia; the distal point of the caudal extension reaches the level of the Alcock canal and the bottom reaches the piriformis, enabling dissection of the obturator nerve and No.283 lymph nodes. No.263D lymph nodes are dissected by exposing the internal iliac artery and its branches, dissecting the group No.263P lymph nodes, and severing the inferior vesical artery. Finally, the lateral lymphatic tissue is completely resected. Relevant variables were recorded, including the number of lateral lymph nodes detected, the rate of lymph node metastasis, operation duration, intraoperative blood loss, postoperative complications, postoperative hospital stay, and 3-year overall survival rate. Results:Laparoscopic surgery was successfully completed in all patients with no conversions to open surgery and no intraoperative complications. Twenty-seven (64.3%) of the study patients underwent left-sided LLND, 10 (23.8%) right-sided LLND, and five (11.9%) bilateral LLND, with lymph nodes cleared on both sides. All patients' lymph nodes were examined pathologically. A median of 17.0 (11.7, 26.0) lymph nodes was detected, the median of lateral lymph nodes being 5.0 (2.0, 10.2). The median operation time was 254.5 (199.0, 325.2) minutes. The median intra-operative blood loss was 50.0 (30.0, 100.0) mL. All patients were diagnosed with adenocarcinoma by pathological examination of the operative specimen. Two patients developed postoperative intestinal obstruction, one lymphatic leakage, and one a perineal incision infection. There were no cases of anastomotic leakage. The median postoperative hospital stay was 6.0 (5.0, 7.0) days and the median follow-up time 23.5 (9.0, 36.7) months. During follow-up, three patients (7.1%) died of tumor recurrence and metastasis. Two (4.8%) experienced mild urinary dysfunction, and one (2.4%) had moderate postoperative erectile dysfunction. One patient (2.4%) was found to have prostate and lung metastases 3 month after surgery. The 3-year overall survival rate was 74.4%.Conclusions:Three sided encapsulation is a safe and feasible procedure for LLND, achieving accurate and complete clearance of lateral lymphatic tissue.
8.Feasibility of a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection for middle and low rectal cancer
Wenjuan LI ; Dechang DIAO ; Jiaxin LIN ; Jiahao WANG ; Weilin LIAO ; Xin TANG ; Jiaxin XIE ; Lin AO ; Xueyang ZHANG ; Xiaojiang YI ; Xiaochuang FENG ; Hongming LI ; Xinquan LU
Chinese Journal of Gastrointestinal Surgery 2023;26(10):968-976
Objective:To explore the feasibility and value of performing a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection (LLND) for middle and low rectal cancer.Methods:This was a retrospective review. The study cohort comprised patients who met the diagnostic criteria for rectal cancer according to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer, had a short lymph node diameter of >5 mm on the lateral side within the 15 days before surgery, were evaluated as feasible candidates for laparoscopic total mesorectal excision+LLND surgery, had been diagnosed with low or intermediate level rectal cancer, and whose tumor was less than 8 cm away from the anal verge according to pathological examination of the operative specimen. Patients with a history of other malignant tumors of the abdomen or with incomplete follow-up data were excluded. Forty-two patients with middle and low rectal cancer who had undergone lateral lymph node dissection in diagnosis and treatment center of Gastrointestinal Cancer of Guangdong Hospital of Chinese Medicine from Jan.2018 to Dec.2022 were enrolled. There were 24 men (57.1%) and 18 women (42.9%) aged 58.4±11.8 years and the median BMI was 22.5 (19.3–24.1) kg/m 2. The main point of the three-sided encapsulation procedure is to expand the external side medial to the external iliac artery and vein, narrowing the range of exterior side dissection. The anterior-medial side is designed to expand the vesical fascia to define the range of anterior-medial side extension. The internal side is fully extended to the ureterohypogastric nerve fascia; the distal point of the caudal extension reaches the level of the Alcock canal and the bottom reaches the piriformis, enabling dissection of the obturator nerve and No.283 lymph nodes. No.263D lymph nodes are dissected by exposing the internal iliac artery and its branches, dissecting the group No.263P lymph nodes, and severing the inferior vesical artery. Finally, the lateral lymphatic tissue is completely resected. Relevant variables were recorded, including the number of lateral lymph nodes detected, the rate of lymph node metastasis, operation duration, intraoperative blood loss, postoperative complications, postoperative hospital stay, and 3-year overall survival rate. Results:Laparoscopic surgery was successfully completed in all patients with no conversions to open surgery and no intraoperative complications. Twenty-seven (64.3%) of the study patients underwent left-sided LLND, 10 (23.8%) right-sided LLND, and five (11.9%) bilateral LLND, with lymph nodes cleared on both sides. All patients' lymph nodes were examined pathologically. A median of 17.0 (11.7, 26.0) lymph nodes was detected, the median of lateral lymph nodes being 5.0 (2.0, 10.2). The median operation time was 254.5 (199.0, 325.2) minutes. The median intra-operative blood loss was 50.0 (30.0, 100.0) mL. All patients were diagnosed with adenocarcinoma by pathological examination of the operative specimen. Two patients developed postoperative intestinal obstruction, one lymphatic leakage, and one a perineal incision infection. There were no cases of anastomotic leakage. The median postoperative hospital stay was 6.0 (5.0, 7.0) days and the median follow-up time 23.5 (9.0, 36.7) months. During follow-up, three patients (7.1%) died of tumor recurrence and metastasis. Two (4.8%) experienced mild urinary dysfunction, and one (2.4%) had moderate postoperative erectile dysfunction. One patient (2.4%) was found to have prostate and lung metastases 3 month after surgery. The 3-year overall survival rate was 74.4%.Conclusions:Three sided encapsulation is a safe and feasible procedure for LLND, achieving accurate and complete clearance of lateral lymphatic tissue.
9.Artificial intelligence-assisted diagnosis and treatment system in prediction of benign or malignant lung nodules and infiltration degree
Mengkun CAO ; Jie JIANG ; Xiaolei ZHU ; Ning LI ; Jianweng WANG ; Junfeng LIN ; Hongming LIU ; Chengqing DENG ; Xiqian CAI ; Guojun GENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(03):283-287
Objective To evaluate the effectiveness of the artificial intelligence-assisted diagnosis and treatment system in distinguishing benign and malignant lung nodules and the infiltration degree. Methods Clinical data of 87 patients with pulmonary nodules admitted to the First Affiliated Hospital of Xiamen University from January 2019 to August 2020 were retrospectively analyzed, including 33 males aged 55.1±10.4 years, and 54 females aged 54.5±14.1 years. A total of 90 nodules were included, which were divided into a malignant tumor group (n=80) and a benign lesion group (n=10), and the malignant tumor group was subdivided into an invasive adenocarcinoma group (n=60) and a non-invasive adenocarcinoma group (n=20). The malignant probability and doubling time of each group were compared and its ability to predict the benign and malignant nodules and the invasion degree was analyzed. Results Between the malignant tumor group and the benign lesion group, the malignant probability was significantly different, and the malignant probability could better distinguish malignant nodules and benign lesions (87.2%±9.1% vs. 28.8%±29.0%, P=0.000). The area under the curve (AUC) was 0.949. The maximum diameter of nodules in the benign lesion group was significantly longer than that in the malignant tumor group (1.270±0.481 cm vs. 0.990±0.361 cm, P=0.026); the doubling time of benign lesions was significantly longer than that of malignant nodules (1 083.600±258.180 d vs. 527.025±173.176 d, P=0.000), and the AUC was 0.975. The maximum diameter of the nodule in the invasive adenocarcinoma group was longer than that of the non-invasive adenocarcinoma group (1.350±0.355 cm vs. 0.863±0.271 cm, P=0.000), and there was no statistical difference in the probability of malignancy between the invasive adenocarcinoma group and the non-invasive adenocarcinoma group (89.7%±5.7% vs. 86.4%±9.9%, P=0.082). The AUC was 0.630. The doubling time of the invasive adenocarcinoma group was significantly shorter than that of the non-invasive adenocarcinoma group (392.200±138.050 d vs. 571.967±160.633 d, P=0.000), and the AUC was 0.829. Conclusion The malignant probability and doubling time of lung nodules calculated by the artificial intelligence-assisted diagnosis and treatment system can be used in the assessment of the preoperative benign and malignant lung nodules and the infiltration degree.
10.Evaluation of drug-drug interactions between yimitasvir phosphate capsules with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets
Jiajia MAI ; Hong ZHANG ; Yuyu PENG ; Xia YANG ; Lei MAO ; Lin LUO ; Hongming XIE ; Yingjun ZHANG ; Xiaojiao LI ; Yanhua DING
Chinese Journal of Hepatology 2020;28(10):838-843
Objective:To evaluate the drug-drug interactions and the tolerability of combined medication between yimitasvir phosphate capsules with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets in healthy volunteers.Methods:A randomized, open, and continuous administration design was used in trial 1 (yimitasvir phosphate capsules with sofosbuvir tablets). 28 subjects were randomly divided into two groups. A non-randomized, open design was used in trial 2 (yimitasvir phosphate capsules with omeprazole magnesium enteric-coated tablets), and included 42 subjects divided into three groups. The open design method was used in trial 3 (yimitasvir phosphate capsules with rosuvastatin calcium tablets), and included 14 subjects. The plasma concentrations of yimitasvir phosphate, sofosbuvir and their main metabolites GS-331007, omeprazole and rosuvastatin were validated by a liquid chromatography/tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by Phoenix winNonlin software.Results:(1) in trial 1, after single and co-administration, the 90% CI of sofosbuvir C max and AUC 0-tau geometric mean ratio (GMR) were 152.0% (118.0% ~ 197.0%) and 230.0% (184.0% ~ 287.0%), with an increase of 52.0% and 130.0% compared to single dose of sofosbuvir, respectively. The 90% CI of GS-331007 C max GMR was 74.0% (67.5% ~ 81.2%) and reduced by 26% compared to single dose of sofosbuvir. (2) in trial 2, the 90% CI of C max GMR after yimitasvir single or co-administration at the same time, with a 4-hours interval, or with a 12- hours interval were 68.9% (44.5% ~ 106.7%) , 64.0% (43.8% ~ 93.6%) and 56.4%(38.9% ~ 81.9%), and the 90% CI of AUC 0-t GMR were 68.6% (46.5% ~ 101.2%), 68.3% (47.6% ~ 98.0%) and 60.5% (41.8% ~ 87.5%), respectively. Compared with single dose of yimitasvir, the C max and AUC 0-t were decreased by 31.1% and 31.4%, 36.0% and 31.7%, 43.6% and 39.5%, respectively. (3) In trial 3, after single and co-administration, the 90% CI of rosuvastatin C max and AUC 0-72 GMR were 172.4% (153.6% ~ 193.5%) and 158.0% (144.3% ~ 172.9%), respectively, with an increase of 74.9% and 60.5% compared to single dose of rosuvastatin. There were no serious adverse events and adverse events leading to withdrawal from the trial. Conclusion:Yimitasvir phosphate capsules have drug-drug interactions with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets.

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