1.CD38 regulates macrophagic cholesterol efflux by promoting lysosome reformation via TFEB
Hao XU ; Xueni SUN ; Tianqi WU ; Jinyuan LIU ; Qianlin HUANG ; Die MO ; Jiaxin WANG ; Shenxian CHEN ; Bodan DENG ; Xiaoyang XU
Chinese Journal of Pathophysiology 2024;40(1):28-37
AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.
2.Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management.
Yao YANG ; Zimu LI ; Ping HUANG ; Jiachan LIN ; Jinyuan LI ; Kexin SHI ; Jiahui LIN ; Jingwen HU ; Zhuoxian ZHAO ; Yongkang YU ; Hongzhong CHEN ; Xiaowei ZENG ; Lin MEI
Acta Pharmaceutica Sinica B 2023;13(8):3454-3470
Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.
3.Treatment of vascular paralysis syndrome with methylene blue during kidney transplantation: one case report
Mei DING ; Weihua LIU ; Jinyuan LI ; Min ZHU ; Ying SUN ; Wenli YU
Chinese Journal of Organ Transplantation 2023;44(5):304-306
The report described one case of vascular paralysis syndrome during kidney transplantation to provide references for clinical practice.After intraoperative opening of kidney artery and vein, the recipient developed vascular paralysis syndrome.However, the efficacy is not obvious after dosing of norepinephrine.After an intravenous infusion of methylene blue, the recipient has a successful removal of tracheal intubation and recovered well.
4.Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase.
Meng CHEN ; Zhengyan GUO ; Jinyuan SUN ; Wei TANG ; Min WANG ; Yue TANG ; Pengwei LI ; Bian WU ; Yihua CHEN
Acta Pharmaceutica Sinica B 2023;13(2):765-774
l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.
5.Effact of 3D simulation on Rhinoplasty Outcomes Evaluation
Jinyuan CHANG ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Fanglin ZENG ; Yuanming YANG ; Ying LIANG ; Yiming HU ; Conghang JIANG ; Xiaofang LI ; Borong FANG
Chinese Journal of Plastic Surgery 2021;37(8):949-952
Objective:To evaluate the effect of preoperative 3D simulation on the evaluation of rhinoplasty.Methods:From December 2017 to March 2019, patients in the Department of Burn and Plastic Surgery of the Second Xiangya Hospital of Central South University were randomly selected as the research subjects. According to whether they had received 3D simulation before surgery, they were divided into the experimental group (after 3D simulation before comprehensive surgery) and the control group (without 3D simulation before comprehensive surgery). Visual analogue scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE ) questionnaires were used to evaluate the satisfaction of all patients preoperative and one month after surgery.Results:At the beginning of this study, a total of 97 cases were included, 97 cases were given questionnaires, and 60 cases were effectively recovered, 30 cases in each group.There was statistical significance in the improvement of the postoperative VAS scores between the experimental group and the control group ( P<0. 05). The mean improvement in the experimental group was (4. 10±0. 88) points, while the mean improvement in the control group was (2. 53±0. 73) points. There was statistical significance in the improvement of the postoperativeROE satisfaction scores between the two groups. The average preoperative satisfaction score of the experimental group was (29. 5±9. 7) points, which increased to (77. 3±13. 7) points after surgery. In the control group, the average satisfaction score was (30. 4±11. 3) points before surgery and increased to (62. 7±23. 4) points after surgery. Conclusions:3D simulation before nasal synthesis can improve the postoperative satisfaction of patients.VAS and ROE questionnaires are good tools for evaluating the effect of comprehensive rhinoplastic surgery.
6.Effact of three-dimentional simulation on rhinoplasty outcomes evaluation
Jinyuan CHANG ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Fanglin ZENG ; Yuanming YANG ; Ying LIANG ; Yiming HU ; Conghang JIANG ; Xiaofang LI ; Borong FANG
Chinese Journal of Plastic Surgery 2021;37(11):1256-1259
Objective:To evaluate the effect of preoperative 3D simulation on the evaluation of rhinoplasty.Methods:From December 2017 to March 2019, patients in the Department of Burn and Plastic Surgery of the Second Xiangya Hospital of Central South University were randomly selected as the research subjects. According to whether they had received 3D simulation before surgery, they were divided into the experimental group (after 3D simulation before comprehensive surgery) and the control group (without 3D simulation before comprehensive surgery). Visual analogue scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) questionnaires were used to evaluate the satisfaction of all patients preoperatively and one month after surgery.Results:At the beginning of this study, a total of 97 cases were included. 97 cases were given questionnaires, and 60 cases were effectively recovered.There were 30 cases in each group. There was statistical significance in the improvement of the postoperative VAS scores between the experimental group and the control group ( P<0.05). The mean improvement in the experimental group was (4.10±0.88) points, while the mean improvement in the control group was (2.53±0.73) points. There was statistical significance in the improvement of the postoperative ROE satisfaction scores between the two groups. The average preoperative satisfaction score of the experimental group was (29.5±9.7) points, which increased to (77.3±13.7) points after surgery.In the control group, the average satisfaction score was (30.4±11.3) points before surgery and increased to (62.7±23.4) points after surgery. Conclusions:3D simulation before nasal synthesis can improve the postoperative satisfaction of patients. VAS and ROE questionnaires are good tools for evaluating the effect of comprehensive rhinoplastic surgery.
7.Viral pathogenic spectrum analysis of severe acute respiratory infection cases in Luohe City, Henan province from 2017 to 2019
Jin XU ; Zhibo XIE ; Jinyuan GUO ; Jinhua SONG ; Pei HE ; Xiaoyu MIN ; Shanshan ZHOU ; Qiang ZHANG ; Kaixuan SUN ; Manli HU ; Baicheng XIA ; Ying LIU ; Jie JIANG ; Zhen ZHU ; Naiying MAO ; Yan ZHANG ; Wenbo XU
Chinese Journal of Preventive Medicine 2021;55(8):931-937
Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.
8.Viral pathogenic spectrum analysis of severe acute respiratory infection cases in Luohe City, Henan province from 2017 to 2019
Jin XU ; Zhibo XIE ; Jinyuan GUO ; Jinhua SONG ; Pei HE ; Xiaoyu MIN ; Shanshan ZHOU ; Qiang ZHANG ; Kaixuan SUN ; Manli HU ; Baicheng XIA ; Ying LIU ; Jie JIANG ; Zhen ZHU ; Naiying MAO ; Yan ZHANG ; Wenbo XU
Chinese Journal of Preventive Medicine 2021;55(8):931-937
Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.
9.Effact of 3D simulation on Rhinoplasty Outcomes Evaluation
Jinyuan CHANG ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Fanglin ZENG ; Yuanming YANG ; Ying LIANG ; Yiming HU ; Conghang JIANG ; Xiaofang LI ; Borong FANG
Chinese Journal of Plastic Surgery 2021;37(8):949-952
Objective:To evaluate the effect of preoperative 3D simulation on the evaluation of rhinoplasty.Methods:From December 2017 to March 2019, patients in the Department of Burn and Plastic Surgery of the Second Xiangya Hospital of Central South University were randomly selected as the research subjects. According to whether they had received 3D simulation before surgery, they were divided into the experimental group (after 3D simulation before comprehensive surgery) and the control group (without 3D simulation before comprehensive surgery). Visual analogue scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE ) questionnaires were used to evaluate the satisfaction of all patients preoperative and one month after surgery.Results:At the beginning of this study, a total of 97 cases were included, 97 cases were given questionnaires, and 60 cases were effectively recovered, 30 cases in each group.There was statistical significance in the improvement of the postoperative VAS scores between the experimental group and the control group ( P<0. 05). The mean improvement in the experimental group was (4. 10±0. 88) points, while the mean improvement in the control group was (2. 53±0. 73) points. There was statistical significance in the improvement of the postoperativeROE satisfaction scores between the two groups. The average preoperative satisfaction score of the experimental group was (29. 5±9. 7) points, which increased to (77. 3±13. 7) points after surgery. In the control group, the average satisfaction score was (30. 4±11. 3) points before surgery and increased to (62. 7±23. 4) points after surgery. Conclusions:3D simulation before nasal synthesis can improve the postoperative satisfaction of patients.VAS and ROE questionnaires are good tools for evaluating the effect of comprehensive rhinoplastic surgery.
10.Effact of three-dimentional simulation on rhinoplasty outcomes evaluation
Jinyuan CHANG ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Fanglin ZENG ; Yuanming YANG ; Ying LIANG ; Yiming HU ; Conghang JIANG ; Xiaofang LI ; Borong FANG
Chinese Journal of Plastic Surgery 2021;37(11):1256-1259
Objective:To evaluate the effect of preoperative 3D simulation on the evaluation of rhinoplasty.Methods:From December 2017 to March 2019, patients in the Department of Burn and Plastic Surgery of the Second Xiangya Hospital of Central South University were randomly selected as the research subjects. According to whether they had received 3D simulation before surgery, they were divided into the experimental group (after 3D simulation before comprehensive surgery) and the control group (without 3D simulation before comprehensive surgery). Visual analogue scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) questionnaires were used to evaluate the satisfaction of all patients preoperatively and one month after surgery.Results:At the beginning of this study, a total of 97 cases were included. 97 cases were given questionnaires, and 60 cases were effectively recovered.There were 30 cases in each group. There was statistical significance in the improvement of the postoperative VAS scores between the experimental group and the control group ( P<0.05). The mean improvement in the experimental group was (4.10±0.88) points, while the mean improvement in the control group was (2.53±0.73) points. There was statistical significance in the improvement of the postoperative ROE satisfaction scores between the two groups. The average preoperative satisfaction score of the experimental group was (29.5±9.7) points, which increased to (77.3±13.7) points after surgery.In the control group, the average satisfaction score was (30.4±11.3) points before surgery and increased to (62.7±23.4) points after surgery. Conclusions:3D simulation before nasal synthesis can improve the postoperative satisfaction of patients. VAS and ROE questionnaires are good tools for evaluating the effect of comprehensive rhinoplastic surgery.

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