1.The diagnostic value of lung ultrasound in children with community-acquired pneumonia
Shujing CAI ; Lele ZHANG ; Siyue CHEN ; Tingting ZHU ; Ming XU ; Yangming ZHENG ; Hailin ZHANG
Chinese Journal of Pediatrics 2024;62(4):331-336
Objective:To investigate the diagnostic value of lung ultrasound in hospitalized children with community-acquired pneumonia (CAP).Methods:In the cross-sectional study, a total of 422 children with CAP who were hospitalized in the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University, from February 2021 to August 2022 and completed lung ultrasound examination within 48 hours after admission were enrolled. The clinical characteristics, lung ultrasound and chest CT were collected. The patients were divided into two groups according to the signs of pneumonia indicated by chest CT, and the signs of lung ultrasound with diagnostic value were screened according to the signs of pneumonia indicated by chest CT by least absolute shrinkage and selection operator (Lasso) regression. According to severity of the disease, the children were divided into the severe group and the mild group, and the differences of lung ultrasound signs between the two groups were compared. Kruskal-Wallis test, Fisher′s exact test was selected for comparison between groups. Random forest classifier wes used to evaluate the value of lung ultrasound in the diagnosis of CAP and prediction of severe pneumonia in children. The receiver operating characteristic curve was used to evaluate the prediction effect. Use DeLong test to compare the area under the curve.Results:Among the 422 cases of CAP, there were 258 males and 164 females, and the age of onset was 2.8 (1.3, 4.3) years. The confluent B-line, consolidation and pleural effusion detected by lung ultrasound were 309 cases (73.2%), 232 cases (55.0%) and 16 cases (3.8%), respectively, and the size of consolidation was 3.0 (0, 11.0) mm. One hundred and ten children (26.1%) with CAP completed chest CT. There were 90 cases with signs of pneumonia in chest CT and 20 cases without signs of pneumonia. Lasso was used for feature selection.Lung consolidation ( OR=2.46), bilateral lung consolidation ( OR=1.16) and confluent B-line ( OR=1.34) were the main index. With random forest classifier, the accuracy of models using full variables and Lasso-selected variables were 0.79 (95% CI 0.70-0.86) and 0.79 (95% CI 0.70-0.86), the sensitivity were 0.81 and 0.81, and the specificity were 0.75 and 0.70, and the area under curve were 0.87 (95% CI 0.81-0.94, P<0.001) and 0.84 (95% CI 0.76-0.91, P<0.001), respectively. There were 97 cases in severe group and 325 cases in mild group. Compared with the mild group, the detection rate of consolidation, multiple consolidation, the size of consolidation and the size of consolidation was adjusted by body surface area (consolidation size/body surface area) in severe group were higher (66 cases (68.0%) vs. 166 cases (51.1%), 42 cases (43.3%) vs. 93 cases (28.6%), 8.0 (0, 17.0) vs. 1.0 (0, 9.0) mm, 12.5 (0, 24.6) vs. 2.1 (0, 17.6), χ2=8.59, 9.98, Z=14.40, 12.79, all P<0.05). Using lung ultrasound lung consolidation size and consolidation size/body surface area to predict the severe CAP, the optimal cut-off value were 6.7 mm and 10.2, the accuracy was 0.80 (95% CI 0.75-0.83) and 0.89 (95% CI 0.86-0.92), the sensitivity was 0.99 and 0.99, the specificity was 0.14 and 0.56, respectively, and the area under the curve was 0.66 (95% CI 0.60-0.72, P<0.001) and 0.76 (95% CI 0.70-0.83, P<0.001), respectively. The area under the curve of consolidation size/body surface area was higher than that of consolidation size ( Z=5.50, P<0.001). Conclusions:Consolidation and confluent B-line, are important index for lung ultrasound diagnosis of CAP in children. The actual consolidation size adjusted by body surface area is superior to the size of consolidation in predicting severe CAP.
2.Analysis of the current status of cancer incidence and mortality in Shanghai,2017 and trends of 2002-2017
Kai GU ; Yi PANG ; Chunxiao WU ; Chunfang WANG ; Liang SHI ; Yongmei XIANG ; Yangming GONG ; Peng PENG ; Jianming DOU ; Mengyin WU ; Xiaocong ZHANG ; Ganling DING ; Jianying YAN ; Yan SHI ; Chen FU
Tumor 2023;43(4):241-256
Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai.This study aimed to investigate the cancer incidence and mortality in 201 7 and their trends from 2002 to 2017 in Shanghai. Methods:Data of new cancer diagnoses and deaths from 2002 to 2017 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Cancer incidence and mortality stratified by year of diagnosis or death,gender and age group were analyzed.Number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.The number,proportion and rates of common cancers in different groups were also calculated.Trends in age-standardized rate of incidence and death rates for all cancers combined and for the common cancer types by gender were estimated by joinpoint analysis and characterized by the annual percent change(APC)and average annual percent change(AAPC).Segi's 1960 world standard population was used for calculating age-standardized incidence and mortality. Results:The new cancer cases and deaths were 79 378 and 37 186 in Shanghai in 2017.The crude rate of incidence was 546.55/105,and the age-standardized rate was 246.31/105.The age-standardized rate of incidence was higher among females than among males.The crude rate of mortality was 256.04/1 05,and the age-standardized rate was 88.41/105.The age-standardized rate of mortality was higher among males than among females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among males reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among females reached the peak at the age groups of older than 85 years,respectively.The sites of top 10 common cancer types sorted by the number of incidence cases among males were lung,colorectum,stomach,prostate,liver,thyroid,pancreas,bladder,kidney and oesophagus,and among females were lung,breast,thyroid,colorectum,stomach,pancreas,liver,brain,central nervous system(CNS),cervix uteri and gallbladder,the sites of those sorted by the number of deaths among males were lung,stomach,colorectum,liver,pancreas,prostate,oesophagus,bladder,lymphoma and gallbladder,among females were lung,colorectum,breast,stomach,pancreas,liver,gallbladder,brain,CNS,ovary and lymphoma.The top 10 common cancer types stratified by gender and the top 5 common cancer types stratified by common age groups merged of incidence and mortality had wide variations.Overall,the age-standardized rates of incidence were stable from 2002 to 2009,and increased 2.88%on average per year from 2009 to 201 7.The age-standardized rates of mortality were stable from 2002 to 2011,and decreased 2.66%on average per year from 2011 to 201 7.The trends differed by gender and cancer type. Conclusion:Lung cancer,colorectal cancer,pancreatic cancer,thyroid cancer,female breast cancer,cervical cancer and male prostate cancer are the most common cancers in Shanghai,the appropriate screening technical scheme should be formulated according to the current situation of malignant tumors in Shanghai,promote cancer opportunistic screening,promote appropriate technologies for intervention and management of cancer patients in the community,reduce the disease burden of malignant tumors.
3.Survival analysis of cancer cases diagnosed during 2002-2013 in Shanghai:a population-based study
Chunxiao WU ; Kai GU ; Yi PANG ; Chunfang WANG ; Liang SHI ; Yongmei XIANG ; Yangming GONG ; Peng PENG ; Jianming DOU ; Mengyin WU ; Xiaocong ZHANG ; Ganling DING ; Jiaying YAN ; Yan SHI ; Chen FU
Tumor 2023;43(4):257-265
Objective:To investigate the survival of cancer cases diagnosed during 2002-2013 in Shanghai. Methods:Data on new cancer cases with dead and follow-up information were obtained from the population-based cancer registry and vital statistics system of Shanghai Municipal Center for Disease Control and Prevention.Survival indicators stratified by year of diagnosis,gender,site and age were analyzed.Number of cases and proportion were calculated.The observed survival rates were calculated based on the life table.The probabilities of surviving from 0 to 99 years old were estimated according to the Elandt-Johnson model,and then the cumulative expected survival rates were calculated according to the Ederer Ⅱ method.Finally,the relative survival rates and average annual percent changes of their trends were calculated.The age-standardized relative survival rates adjusted by International Cancer Survival Standard weights were calculated. Results:Total 644 520 new cancer cases were diagnosed during 2002-2013 in Shanghai,accounting for 643 545(99.85%)cases included in the observed cohort for survival analysis.The 5-year observed survival rate increased from 37.61%to 46.47%.The 5-year relative survival rate increased from 42.1 8%to 51.11%.The 5-year age-standardized relative survival rate increased from 40.57%to 49.80%.Among the 5-year relative survival rates of cases diagnosed during 2011 to 2013,99.43%of thyroid cancer was the highest,followed by female breast cancer(88.35%)and corpus uteri cancer(85.56%);5.87%of pancreas cancer was the lowest,followed by gallbladder cancer(13.64%)and oesophagus cancer(17.72%).the rate of lung cancer with the largest number of cases was 23.59%,followed by colorectal cancer(59.82%)and stomach cancer(38.65%).The 5-year relative survival rate of total cases of all sites increased from 40.55%in 2002 to 52.77%in 2013,with an average annual percent change of 2.40%.13 cancer types showed increasing trends,such as liver cancer and lung cancer,while the trends of other cancer types were not statistically significant,such as pancreatic cancer and gallbladder cancer. Conclusion:The diagnostic levels and survival rates of cancer cases have been improved continuously in Shanghai.The trends of different cancer types were varied.
4.The incidence and mortality of lung cancer in 2016 and their trends from 2002 to 2016 in Shanghai
Jianming DOU ; Chunxiao WU ; Yi PANG ; Pingping BAO ; Chunfang WANG ; Yangming GONG ; Liang SHI ; Yongmei XIANG ; Mengyin WU ; Xiaocong ZHANG ; Yan SHI ; Chen FU ; Kai GU
Tumor 2023;43(4):266-276
Objective:To investigate the lung cancer incidence and mortality in 2016 and their trends from 2002 to 2016 in shanghai. Methods:The data of incidence and death on lung cancer in shanghai from 2002 to 2016 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Lung Cancer incidence and mortality stratified by age of diagnosis or death,gender and age-group were analyzed.The number of cases and deaths,proportion,crude rates,age-specific rates,age-standardized rates,corresponding truncated age-standardized rates(35-64 years)and cumulative rates were calculated.Segi's 1960 world standard population was used for calculating age-standardized rates of incidence and mortality as well as truncated age-standardized rates.Trends in age-standardized rates of incidence and death for lung cancer in Shanghai from 2002-2016 were estimated by Joinpoint analysis and characterized by the annual percent change(APC). Results:The new lung cancer cases and deaths were 14 395 and 9 170 in Shanghai in 2016.The crude rate of incidence was 99.41/105,and the age-standardized rate of incidence was 39.76/105.New cases of lung cancer accounted for 19.34%of all malignant tumors in shanghai,ranking the first in the incidence spectrum of malignant tumors.The crude rate of mortality was 63.33/105,and the age-standardized rate was 21.57/105.Deaths of lung cancer accounted for 24.78%of all malignant tumor deaths in shanghai,ranking the first in the mortality spectrum of malignant tumors.The age-standardized rates of incidence and mortality for males were higher than those for females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age group of 60-64 years and 80-84 years respectively,and those of mortality peaked at the age group of 80-84 years and older than 85 years respectively.The incidence of lung cancer increased from 33.70/105 in 2002 to 39.76/1 05 in 2016 in Shanghai.Joinpoint analyses showed that the age-standardized rate of lung cancer incidence remained stable from 2002 to 2010(APC=-0.79,t=-1.46,P=0.175)but showed a significant upward trend with an average annual increase rate of 5.12%from 2010 to 2016(APC=5.12,t=6.97,P<0.001).The standardized mortality showed a downward trend with an average annual decrease rate of 0.87%from 2002 to 2016(APC=-0.87,t=-2.87,P=0.013). Conclusion:The incidence of lung cancer in Shanghai during 2002-2016 presented an upward trend while the mortality of lung cancer showed a gradual downward trend.There are differences in the incidence and mortality of lung cancer among different gender and age groups.
5.Analysis on the current status of liver cancer incidence and mortality in Shanghai,2016 and trends during 2002-2016
Liang SHI ; Kai GU ; Chunxiao WU ; Yi PANG ; Yangming GONG ; Yongmei XIANG ; Jianming DOU ; Xiaocong ZHANG ; Mengyin WU ; Chunfang WANG ; Yan SHI ; Chen FU
Tumor 2023;43(4):277-286
Objective:To investigate the liver cancer incidence and mortality in 2016 and their trends during 2002 through 2016 in Shanghai. Methods:Data on new liver cancer diagnoses and deaths during 2002 through 2016 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System,the numbers,crude rates and age-standardized rates of incidence and mortality of liver cancer were calculated.Segi's 1960 world standard population was used to calculate age-standardized rates.Joinpoint analysis was used to analyze the trend changes and to estimate the annual percent change of incidence and mortality rates. Results:There were 3 842 new liver cancer cases in Shanghai in 201 6,69.44%of which were males,and 3 275 deaths of liver cancer,69.44%of which were males.Mortality to incidence ratio was 0.85.The crude rate of incidence was 26.53/105,and the age-standardized rate was 10.60/105.The crude rate of mortality was 22.62/105,and the age-standardized rate was 8.65/105.The Sex ratios for age-standardized incidence and mortality were 2.91∶1 and 2.97∶1,respectively.The age-specific numbers and rates of incidence and mortality increased with age.Overall,the age-standardized rate of incidence of liver cancer was decreased 3.69%on average per year during 2002 through 2016,and the age-standardized rate of mortality of liver cancer was decreased 3.82%on average per year. Conclusion:The incidence and mortality of liver cancer in Shanghai have been remarkably decreased to a low level countrywide,while liver cancer is still one of the leading malignancies and it brings serious threat to public health,comprehensive prevention and control efforts should be strengthened according to its epidemic characteristics and risk factors.
6.Incidence and mortality of esophageal cancer in Shanghai 2016 and changing trend analysis from 2002 to 2016
Xiaocong ZHANG ; Peng PENG ; Chunxiao WU ; Yi PANG ; Chunfang WANG ; Mengyin WU ; Yangming GONG ; Ganling DING ; Chen FU ; Yan SHI ; Kai GU
Tumor 2023;43(4):287-296
Objective:More than half of esophageal cancer incidences and deaths occurred in China.Based on the Shanghai Tumor Registration data,this study analyzed the incidence and mortality of esophageal cancer in Shanghai in 2016 and the changing trend from 2002 to 2016,in order to provide an epidemic basis for the prevention and treatment of esophageal cancer. Methods:Data on esophageal cancer in Shanghai from 2002 to 2016 were obtained through Shanghai Municipal Center for Disease Control and Prevention Population-based Cancer Registry and Vital Statistics System.The number of cases and deaths,crude rates,composition ratios,age-specific rates and cumulative rates were counted according to the year of diagnosis or death,gender and age groups.Segi's 1960 world standard population was used to calculate age-standardized rates of incidence and mortality,and corresponding truncated age-standardized rate(35-64 years old)on esophageal cancer.Z-test and Cochran test were used to compare the differences of age-specific rates and age-standardized rates among different subgroups,respectively.Temporal trend analyses were conducted by Joinpiont 4.9.1.0 software. Results:In 2016,the proportion of morphological verification of new cases of esophageal cancer in Shanghai was 73.1 8%,the proportion of death certificate only was 0.72%,and the ratio of death to incidence was 0.84.The number of new cases and deaths of esophageal cancer in Shanghai in 2016 were 1 398 and 1 171,accounting for 1.88%and 3.1 6%of all malignant tumors,respectively.The crude incidence and mortality of esophageal cancer were 9.65/100 000 and 8.09/100000,with age-standardized incidence and mortality of 3.36/100 000 and 2.67/100,000,respectively.The age-standardized incidence and mortality were significantly higher in males than in females.The age-specific incidence and mortality increased with age,and peaked at 50.54/100 000 and 53.35/1 00 000,respectively,among people aged 85 years and older.From 2002 to 2016,both the number of new cases and deaths of esophageal cancer in Shanghai showed a downward trend,and the age-standardized incidence and mortality also showed a downward trend,with an average annual deceleration of 4.45%[annual percent change(APC)=-4.45,P<0.001]and 4.1 7%(APC=-4.17,P<0.001),respectively. Conclusion:The incidence and mortality of esophageal cancer in Shanghai were at a low epidemic level across China,and showed a downward trend from 2002 to 2016.Esophageal cancer screening should focus on males and subjects aged 55 to 64 years.
7.Colorectal cancer incidence and mortality trends in urban Shanghai,China from 1973 to 2017:a Joinpoint regression and age-period-cohort analysis
Mengyin WU ; Kai GU ; Chunxiao WU ; Yi PANG ; Chunfang WANG ; Yangming GONG ; Peng PENG ; Jianming DOU ; Xiaocong ZHANG ; Yongmei XIANG ; Yan SHI ; Yingbin LIU ; Chen FU
Tumor 2023;43(4):325-336
Objective:To describe the epidemiological features and temporal trends of colorectal cancer in urban Shanghai from 1973 to 2017. Methods:Data on colorectal cancer in urban Shanghai was obtained through Shanghai Cancer Registry and Vital Statistics System.Joinpoint analysis was used to describe the temporal trends and annual percent change(APC)and age-period-cohort analysis was used to estimate the association between age,period and birth cohort and colorectal cancer. Results:A total of 105 847 cases and 60 447 deaths of colorectal cancer were diagnosed in urban Shanghai over the 45-year study period.Both the number of new cases and the number of deaths showed an increasing trend.In the same period,the age-standardized incidence of colorectal cancer in urban areas of Shanghai increased significantly from 14.1/100 000 in 1973 to 27.7/100 000 in 2017,while the age-standardized mortality rate increased from 8.2/100 000 to 10.7/100 000.The overall average annual age-standardized incidence and mortality rates were 20.4/100 000 and 11.0/100 000,respectively.With the increase of age,the age-standardized morbidity and mortality of colorectal cancer showed an obvious upward trend.Taking 1993-1997 as reference,the risk of colorectal cancer in Shanghai reached the highest in 2013-2017,and the corresponding relative risk was 1.2(95%confidence interval:1.2-1.3),while the lowest was 0.9(95%confidence interval:0.8-1.0)during 1973-1977.Mortality risk,on the contrary,decreased with the increase of time.Before 1953-1957,the risk of colorectal cancer in urban Shanghai increased with the increase of birth cohort time,and then showed a downward trend.There was a corresponding decline in the risk of colorectal cancer death among people born after 1957. Conclusion:The incidence and mortality of colorectal cancer in Shanghai showed an increasing trend from 1973 to 2017,but the prevalence trend of colorectal cancer is still different among different populations.
8.Can lung ultrasound replace the chest X-ray? A prospective multicenter study
Yangming QU ; Shuyu SI ; Huiqing SUN ; Pingyang CHEN ; Qianshen ZHANG ; Li MA ; Zhaoqing YIN ; Min XIAO ; Jimei WANG ; Xirong GAO ; Ling LIU ; Jinxing FENG ; Yanping ZHU ; Di JIN ; Jing ZHANG ; K. Shoo LEE ; Hui WU
Chinese Pediatric Emergency Medicine 2023;30(11):834-839
Objective:To analyze the accuracy of lung ultrasound and chest X-ray in the diagnosis of neonatal pulmonary disease.Methods:We prospectively collected newborns that needed chest X-ray examination to diagnose pulmonary disease from twelve neonatal intensive care units across the country between June 2019 and April 2020.Each newborn was examined by lung ultrasound within two hours after chest X-ray examination.All chest X-ray and lung ultrasound images were independently read by a radiologist and a sonographer.When there was a disagreement, a panel of two experienced physicians made a final diagnosis based on the clinical history, chest X-ray and lung ultrasound images.Results:A total of 1 100 newborns were enrolled in our study.The diagnostic agreement between chest X-ray and lung ultrasound(Cohen′s kappa coefficient=0.347) was fair.Lung ultrasound(area under the curve=0.778; 95% CI 0.753-0.803) performed significantly better than chest X-ray(area under the curve=0.513; 95% CI 0.483-0.543) in the diagnosis of transient tachypnea of the newborn( P<0.001). The accuracy of lung ultrasound in diagnosing neonatal respiratory distress syndrome, meconium aspiration syndrome, pneumonia and neonatal pulmonary atelectasis was similar to that of chest X-ray. Conclusion:Lung ultrasound, as a low-cost, simple and radiation-free auxiliary examination method, has a diagnostic accuracy close to or even better than that of chest X-ray, which may replace chest X-ray in the diagnosis of some neonatal lung diseases.It should be noted that both chest X-ray and lung ultrasound can only be used as auxiliary means for the diagnosis of lung diseases, and it is necessary to combine imaging with the clinical history and presentation.
9.Study on the harvest time of Astragali Radix and the revision of the content determination index in Chinese Pharmacopoeia
Pengpeng LIU ; Ji SHI ; Fan ZHANG ; Zixuan NIE ; Yangming WANG ; Hui ZHU
International Journal of Traditional Chinese Medicine 2023;45(7):868-874
Objective:To compare the quality of Astragali Radix at different harvest time; To revise the content determination indexes of Astragali Radix in Chinese Pharmacopoeia. Methods:An Agilent Eclipse XDB-C18 column (4.6 mm × 150 mm, 5 μm) was used for the determination of saponins with acetonitrile-water solution as mobile phase in a gradient mode. The drift tube temperature of ELSD was 60 ℃; the pressure was 30 psi; the gain was 800 ℃; the flow rate was 1.0 ml/min; the column temperature was 30 ℃; the injection volume was 20 μl; the acetonitrile-0.2% formic acid solution was used as mobile phase for the determination of flavonoids in a gradient mode; the flow rate was 1.0 ml/min; the detection wavelength was 260 nm; the column temperature was 30 ℃; the 10 μl was injected. The limited range as an indicator for determining Astragali Radix content was determined by investigating the extraction method and extraction time of Astragaloside Ⅰ and detecting the content of Astragaloside Ⅰ in 12 batches of Astragali Radix from different origins. The moisture, total ash, and water-soluble extracts in Astragali Radix were determined according to the drying method, total ash determination method, and cold soaking method in the four parts of Chinese Pharmacopoeia (2020 edition), respectively. Results:The content of total saponins in Astragali Radix harvested in spring and autumn in different origins was not significantly different, but the content of total flavonoids was significantly different. Except for H11, the content of Astragaloside Ⅰ in the other batches of Astragali Radix was ≥ 0.05%, so the content limit of Astragaloside Ⅰ was proposed to be≥0.05%. The results of moisture, total ash and water-soluble extracts in the 12 batches of Astragali Radix all meet the requirements in the Chinese Pharmacopoeia. Conclusions:Astragali Radix harvested in autumn is with higher content of active components and better quality. At the same time, this study can provide a reference that the new version of Chinese Pharmacopoeia can revise the Astragaloside Ⅳ in the content determination index of Astragali Radix to Astragaloside Ⅰ .
10.Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia.
Zhifu XIE ; Mei ZHANG ; Qian SONG ; Long CHENG ; Xinwen ZHANG ; Gaolei SONG ; Xinyu SUN ; Min GU ; Chendong ZHOU ; Yangming ZHANG ; Kexin ZHU ; Jianpeng YIN ; Xiaoyan CHEN ; Jingya LI ; Fajun NAN
Acta Pharmaceutica Sinica B 2023;13(2):739-753
Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC50 = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

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