1.The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia.
Jian LU ; Xuyang SHANG ; Bingyi YAO ; Dongyi SUN ; Jie LIU ; Yuanjin ZHANG ; He WANG ; Jingru SHI ; Huaqing CHEN ; Tieliu SHI ; Mingyao LIU ; Xin WANG
Acta Pharmaceutica Sinica B 2023;13(2):648-661
Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
2.Application of flipped classroom teaching mode in community clinical pharmacist training
Yanru LIU ; Jingru GONG ; Tongtong ZHANG ; Huiping LU ; Jianfeng LI ; Deduo XU
Chinese Journal of Medical Education Research 2023;22(8):1242-1245
Objective:To explore the application and effect of flipped classroom in community clinical pharmacist training.Methods:Seventeen pharmacists trained in 2017-2018 were used as the control group and received traditional teaching mode. Fourteen pharmacists trained in 2019-2020 were used as the experimental group and received the flipped classroom teaching mode. Finally, the teaching effect was evaluated through the trainees' graduation examination results and satisfaction degree. The SPSS 25.0 was used to conduct the t test and chi-square test. Results:The task performance, prescription audit scores, clinical practice scores, and total scores in the experimental group were significantly higher than those in the control group ( P<0.05). However, there was no significant difference in usual performance between the two groups ( P>0.05). For satisfaction survey, the total score of Likert scale in the experimental group was (20.1±3.4), which was significantly higher than that in the control group (16.9±3.4). However, there was no significant difference in the satisfaction of clinical practice and teachers' level between the two groups ( P>0.05). Conclusion:Flipped classroom can improve the enthusiasm of community clinical pharmacist trainees to participate in learning, increase the level of the trainees' theoretical knowledge and professional practice, and is conducive to the cultivation of high-quality community clinical pharmacists.
3.Functional magnetic resonance imaging study of drug-resistant medial temporal lobe epilepsy
Jingru HAO ; Qiang XU ; Qirui ZHANG ; Fang YANG ; Kangjian SUN ; Guangming LU ; Zhiqiang ZHANG
Chinese Journal of Neurology 2022;55(1):41-46
Objective:To explore the changes of brain activity in drug-resistant or drug-controlled medial temporal lobe epilepsy patients by the method of functional connectivity density (FCD), and to analyze their correlation with the course of the disease.Methods:According to the definition of drug-resistant epilepsy by the International League Against Epilepsy in 2010, 146 patients with medial temporal lobe epilepsy who were clearly diagnosed as unilateral hippocampal sclerosis in Jinling Hospital, Nanjing University School of Medicine from July 2009 to February 2019 were divided into drug control group ( n=73) and drug-resistant group ( n=73). The 3.0 T resting state functional magnetic resonance scan was performed on all subjects to compare the difference in FCD between the two groups, and calculate the correlation between the FCD value of the brain area and the course of the disease between the two groups of patients. Results:There was significant difference between the two groups in FCD. Compared with the drug control group, the drug-resistant group had significantly lower FCD values in the insula, lenticular nucleus, thalamus, hippocampus and precentral gyrus on the side of the epileptogenic focus. The FCD value of the precuneus on the side of the epileptogenic focus in the drug-resistant group was negatively correlated with the duration ( r=-0.30, P=0.01). Conclusions:The FCD of patients with drug-resistant medial temporal lobe epilepsy was lower than that of the drug control group. In addition, there may be progressive damage to the brain. The difference is helpful for exploring the pathophysiological mechanisms related to drug resistance in patients with medial temporal lobe epilepsy, and finding reliable neuroimaging markers related to drug resistance.
4.Integrated metabolism and epigenetic modifications in the macrophages of mice in responses to cold stress.
Jingjing LU ; Shoupeng FU ; Jie DAI ; Jianwen HU ; Shize LI ; Hong JI ; Zhiquan WANG ; Jiahong YU ; Jiming BAO ; Bin XU ; Jingru GUO ; Huanmin YANG
Journal of Zhejiang University. Science. B 2022;23(6):461-480
The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.
Acetylation
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Animals
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Cold-Shock Response
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Epigenesis, Genetic
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Macrophages/metabolism*
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Mice
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Mitochondria/metabolism*
5.Determination of lanthanum in whole blood by microwave digestion-inductively coupled plasma optical emission spectrometry
Jingru ZHANG ; Junjie HUA ; Ling HAN ; Min ZHU ; Ying LU
Journal of Pharmaceutical Practice 2021;39(2):118-120
Objective To evaluate the transdermal safety of lanthanum (La) in sunscreen and jellyfish sting protective lotion, establish a microwave digestion-inductively coupled plasma opticalemission spectroscopy (ICP-OES) method for determination of lanthanum (La) in rat’s whole blood. Methods The whole blood samples were digested by microwave and analyzed by inductively coupled plasma emission spectrometer (ICP-OES). Using 333.749 nm as the analysis line, the content of La in rat whole blood was determined. Results The correlation linearity of the standard curve of this method was good (r>0.9994), the detection limit of the method was 0.0025 μg/ml, the limit of quantification was 0.0077 μg/ml, the precision was less than 3%, and the recovery rate was between 94.9% and 102.0%. Conclusion The ICP-OES method based on microwave digestion is stable and reliable, and can provide an important basis for the study of the transdermal safety of lanthanum.
6.Value of multi-label learning MRI model assisting radiological diagnosis of sports injury in knee
Guang LIN ; Qirui ZHANG ; Yuexiang LI ; Jianrui LI ; Jingru HAO ; Qiang XU ; Kai MA ; Guangming LU ; Zhiqiang ZHANG
Chinese Journal of Radiology 2021;55(11):1191-1196
Objective:To construct a multi-label learning MRI model for assisting diagnosis of sports injury in knee.Methods:A total of 1 391 knee MRI cases from 1 343 young adults with sports injury in Affiliated Jinling Hospital Nanjing University School of Medicine were retrospectively enrolled. The image cases were randomly divided into training set ( n=973), validation set ( n=139) and test set ( n=279) with ratio of 7∶1∶2. The knee injuries were divided into six categories: meniscus injury, tendon injury, ligament injury, osteochondral injury, synovial bursa disorder and soft tissue injury. Using PyTorch V1.1.0 algorithm package, the Yolo model of deep learning was used to construct the MRI knee joint sports injury detection model. The model was validated on the test set, and the sensitivity, specificity and mean average precision of lesion detection were evaluated. Results:Among the 279 patients in test set, the mean average precision of meniscus injury, tendon injury, ligament injury, osteochondral injury, synovial bursa disorder and soft tissue injury were 83.1%, 89.0%, 88.0%, 85.8%, 85.5% and 83.2%, respectively, and the overall mean average precision was 85.8%. The model was most effective in detecting tendon injury. The sensitivity and specificity of the model for tendon injury were 91.2% and 87.1% respectively.Conclusions:The multi-label MRI knee joint exercise-related injury detection model based on deep learning can effectively assist in detecting the exercise-related injury of knee joint in each tissue structure, and is expected to improve the efficiency of diagnosis and treatment in orthopedics.
7.Effect of auricular combined with rhubarb powder acupoint application on improving the quality of bowel preparation in colonoscopy patients
Jie LI ; Juan CHENG ; Yunshan DUAN ; Huiying LI ; Jingru LI ; Yingjuan ZHANG ; Yeli LU ; Qian ZHAO
International Journal of Traditional Chinese Medicine 2021;43(7):658-662
Objective:To explore the effect of auricular point pressing pill combined with rhubarb acupoint application on intestinal preparation and prevention of adverse events in colonoscopy.Methods:A total of 220 patients who met the inclusion criteria from May 2019 to February 2020 were randomly divided into 4 groups, 55 in each group. The control group was only given compound polyethylene glycol electrolyte powder. The auricular plaster group was combined with auricular point pressing pill on the basis of the control group. The acupoint sticking group was combined with rhubarb acupoint application on the basis of the control group. The combination group was combined with auricular point pressing pill and rhubarb acupoint application on the basis of the control group. The quality of bowel preparation was evaluated by Boston Bowel Preparation Scale(BBPS), and the adverse events such as perianal discomfort, defecation discomfort, abdominal pain and abdominal distension were observed.Results:After treatment, there was significant difference in BBPS score among the four groups ( F=3.038, P=0.030). The BBPS score in the acupoint sticking group (7.45 ± 1.20 vs. 6.78 ± 1.32) and combination group (7.26 ± 1.11 vs. 6.78 ± 1.32) were significantly higher than those in the control group( P<0.05). After treatment, there were significant differences in abdominal pain and abdominal distension scores among the four groups ( F=2.947, 5.879, P=0.034, 0.001). The scores of perianal discomfort (0.07 ± 0.38 vs. 0.44 ± 1.07), defecation discomfort (0.40 ± 0.81 vs. 0.87 ± 1.32) and abdominal pain (0.93 ± 1.32 vs. 1.69 ± 1.61) in the combination group were significantly lower than those in the control group ( P<0.05), and the abdominal distension score (1.05 ± 1.00 vs. 1.64 ± 0.95) in the acupoint sticking was significantly lower than that of the control group ( P<0.05). Conclusion:Auricular combined with rhubarb powder acupoint application can improve the quality of bowel preparation and reduce intestinal adverse reactions. It can be used with polyethylene glycol electrolyte powder for the intestinal preparation process.
8.Construction and effect evaluation of tuberculosis information platform in Ningxia
Xiaolin WANG ; Juan LEI ; Xiaowei WANG ; Tao LIU ; Jingru LU ; Xiaomei TIAN
Chinese Journal of Preventive Medicine 2021;55(4):517-520
Objective:To explore the value of information technology in management of tuberculosis patients.Methods:The data comes from the case reports of Ningxia tuberculosis patients in the national tuberculosis special report system from March to December 2019 and the data of Ningxia tuberculosis information management platform. Using the computer Information and communication technologies and the Internet platform, unified data collection and data interface standards,Hospital Information System(HIS) of 18 (90%)TB specific Hospitals in Ningxia 22 counties are linked together, forming a closed loop management System, to realize Information interconnection, compare the patients′ diagnostic rate before and after the application, and standardize treatment differences.Results:The system automatically collected and uploaded valid data for 2 918 times, and the consistency rate of uploaded data was 94.8%.The clinical diagnostic rate was 18.23% (1 154/6 332) before and 39.1% (914/2 335) after using the AI imaging screening subsystem (χ2=235.56, P<0.001).The regular medication rate of patients after system use was 86.89% (510/587), which was higher than that before [73.72% (544/738)] (χ2=3.94, P<0.05).The cure rate of etiologically positive tuberculosis patients (2019) was 86.03% (788/916), which was higher than that of 83.45% (1 008/1 208) before the use of the system (2018) (χ2=435.43, P<0.001). Conclusion:The tuberculosis information management platform in Ningxia has achieved tuberculosis information interconnection, significantly improving the standard diagnosis, treatment and management level of tuberculosis.
9.Construction and effect evaluation of tuberculosis information platform in Ningxia
Xiaolin WANG ; Juan LEI ; Xiaowei WANG ; Tao LIU ; Jingru LU ; Xiaomei TIAN
Chinese Journal of Preventive Medicine 2021;55(4):517-520
Objective:To explore the value of information technology in management of tuberculosis patients.Methods:The data comes from the case reports of Ningxia tuberculosis patients in the national tuberculosis special report system from March to December 2019 and the data of Ningxia tuberculosis information management platform. Using the computer Information and communication technologies and the Internet platform, unified data collection and data interface standards,Hospital Information System(HIS) of 18 (90%)TB specific Hospitals in Ningxia 22 counties are linked together, forming a closed loop management System, to realize Information interconnection, compare the patients′ diagnostic rate before and after the application, and standardize treatment differences.Results:The system automatically collected and uploaded valid data for 2 918 times, and the consistency rate of uploaded data was 94.8%.The clinical diagnostic rate was 18.23% (1 154/6 332) before and 39.1% (914/2 335) after using the AI imaging screening subsystem (χ2=235.56, P<0.001).The regular medication rate of patients after system use was 86.89% (510/587), which was higher than that before [73.72% (544/738)] (χ2=3.94, P<0.05).The cure rate of etiologically positive tuberculosis patients (2019) was 86.03% (788/916), which was higher than that of 83.45% (1 008/1 208) before the use of the system (2018) (χ2=435.43, P<0.001). Conclusion:The tuberculosis information management platform in Ningxia has achieved tuberculosis information interconnection, significantly improving the standard diagnosis, treatment and management level of tuberculosis.
10.Mutation analysis of 5 children with primary distal renal tubular acidosis
Ruixiao ZHANG ; Yanhua LANG ; Yanxia GAO ; Zeqing CHEN ; Cui WANG ; Jingru LU ; Leping SHAO
Chinese Journal of Nephrology 2018;34(6):410-417
Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA),and explore their association of genotype and phenotype,so as to raise the awareness of the disease.Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families.Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children,including a novel heterozygous intron mutation (c.639 + 1G> A),a reported heterozygous nonsense variant (c.580C >T,p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT,p.Tyr502Leufs*22;c.2351dupT,p.Phe785Ilefs*28).Two novel heterozygous missense mutations of ATP6V 1B 1 gene (c.409C > T,p.Pro 137Ser;c.904C > T,p.Arg302Trp) were identified in the third child,and a heterozygous missense mutation of SLC4A1 gene (c.1765C > A,p.Arg589Ser) previously reported was found in the fourth child.No mutation of the dRTA-related causal genes was found in the fifth child.Furthermore,the mutations of causal genes in each of the first three children were compound heterozygous,which were consistent with the autosomal recessive inheritance pattern,and the variant from the fourth child was de novo.Conclusions The present study has found 7 mutations,including 5 novel variants,which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.

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