1.Diabetes-associated sleep fragmentation impairs liver and heart function via SIRT1-dependent epigenetic modulation of NADPH oxidase 4.
Yuanfang GUO ; Jie WANG ; Dongmei ZHANG ; Yufeng TANG ; Quanli CHENG ; Jiahao LI ; Ting GAO ; Xiaohui ZHANG ; Guangping LU ; Mingrui LIU ; Xun GUAN ; Xinyu TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(3):1480-1496
Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.
2.Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.
Xiaohui ZHANG ; Xinyu TANG ; Ting GAO ; Yuanfang GUO ; Guangping LU ; Qingbo LIU ; Jiahao LI ; Jie WANG ; Mingrui LIU ; Dongmei ZHANG ; Yufeng TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(7):3591-3610
A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO +/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.
3.Central nervous system infection:Expert consensus on imaging examination standards(2024 edition)
Chen QIAO ; Ting LIU ; Jianming CAI ; Qing LU ; Weijun SITU ; Meng ZHENG ; Zhenying XIA ; Yuan QU ; Ting LIANG ; Guangping ZHENG ; Hongkai ZHANG ; Shengyuan LAI ; Hongjun LI
Chinese Journal of Medical Imaging Technology 2025;41(6):857-860
Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.
4.Central nervous system infection:Expert consensus on imaging examination standards(2024 edition)
Chen QIAO ; Ting LIU ; Jianming CAI ; Qing LU ; Weijun SITU ; Meng ZHENG ; Zhenying XIA ; Yuan QU ; Ting LIANG ; Guangping ZHENG ; Hongkai ZHANG ; Shengyuan LAI ; Hongjun LI
Chinese Journal of Medical Imaging Technology 2025;41(6):857-860
Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.
5.The challenging blood cross-matching and resolution for multiple myeloma patients in different disease stages
Ying LU ; Baoying FENG ; Lijuan XU ; Peibin LAI ; Lingling LIU ; Guangping LUO ; Qing YUAN
Chinese Journal of Blood Transfusion 2022;35(3):257-261
【Objective】 To explore the challenging blood cross-matching and resolution for multiple myeloma (MM) patients in different disease stages. 【Methods】 For a patient who was first diagnosed as MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method and tube test. When the major side of cross-matching was agglutinated, the patient’s plasma was cross matched with donors’ red blood cell (RBC) by polybrene test, then plasma dilution cross matched with donors’ RBC by microcolumn gel method. For a patient who was diagnosed as recurrent refractory MM and scheduled for blood transfusion, his blood was cross matched with donors’ blood by microcolumn gel method. 【Results】 1) Case 1 was a first-visit outpatient. The major side of microcolumn cross-match test was agglutinated with the shape of fine line. The result of tube method also showed agglutination of major sides, and the rouleaux were detected by the microscopy. Then polybrene method and microcolumn gel method (after plasma diluted) were applied for cross-matching again with the above two donors’ blood and showed compatibility. 2) Case 2 was a recurrent refractory MM patient. The major and minor sides of microcolumn cross-match test were both agglutinated with the shape of granular. The patient was treated with anti-CD38 monoclonal antibody. The RBCs, after treated with dithiothreitol (DTT) was used to cross match with patient plasma by microcolumn test, and the result was compatible. 【Conclusion】 Polybrene method and microcolumn gel method after plasma diluted are suitable for blood cross-matching of newly diagnosed MM patients, also for those treated with CD38 monoclonal antibody, as the drug interference with cross-matching can be eliminated by DTT.
6.Acute pancreatitis induced by tacrolimus in a patient after kidney transplantation
Guangping LI ; Jiangtao WU ; Qi WANG ; Bo CUI ; Xu WANG ; Lu LU ; Tongwen OU
Adverse Drug Reactions Journal 2022;24(4):213-215
A 38-year-old female patient with uraemia received tacrolimus 1 mg orally twice daily after kidney transplantation. The serum trough concentration of tacrolimus was 9.8 μg/L on the 15th day. On the 17th day, the patient developed abdominal pain, nausea, and vomiting. The abdominal CT showed that the volume of pancreas increased, the edge was irregular, and obvious exudation appeared around the pancreas and in the abdominal cavity. Laboratory tests showed blood amylase 430 U/L and lipase 231 U/L.The acute pancreatitis related to tacrolimus was considered. Tacrolimus was stopped and replaced by cyclosporine A 100 mg orally twice daily. Meanwhile, symptomatic and supportive treatments such as fasting, gastrointestinal decompression, lipid-lowering, acid inhibition, anti-infection, and parenteral nutrition were given. Three days later, the above symptoms were relieved. Nineteen days later, laboratory tests showed blood amylase 173 U/L and lipase 51 U/L; abdominal CT showed that the outline of the pancreas was clearer than before, and the exudation around was significantly reduced.
7.Acute pancreatitis induced by tacrolimus in a patient after kidney transplantation
Guangping LI ; Jiangtao WU ; Qi WANG ; Bo CUI ; Xu WANG ; Lu LU ; Tongwen OU
Adverse Drug Reactions Journal 2022;24(4):213-215
A 38-year-old female patient with uraemia received tacrolimus 1 mg orally twice daily after kidney transplantation. The serum trough concentration of tacrolimus was 9.8 μg/L on the 15th day. On the 17th day, the patient developed abdominal pain, nausea, and vomiting. The abdominal CT showed that the volume of pancreas increased, the edge was irregular, and obvious exudation appeared around the pancreas and in the abdominal cavity. Laboratory tests showed blood amylase 430 U/L and lipase 231 U/L.The acute pancreatitis related to tacrolimus was considered. Tacrolimus was stopped and replaced by cyclosporine A 100 mg orally twice daily. Meanwhile, symptomatic and supportive treatments such as fasting, gastrointestinal decompression, lipid-lowering, acid inhibition, anti-infection, and parenteral nutrition were given. Three days later, the above symptoms were relieved. Nineteen days later, laboratory tests showed blood amylase 173 U/L and lipase 51 U/L; abdominal CT showed that the outline of the pancreas was clearer than before, and the exudation around was significantly reduced.
8.Infection of Oligochaetes, Limnodrilus hoffmeisteri (Annelida: Oligochaeta), in the Nasal Cavity of a Chinese Man.
Hongbin LIU ; Zhenming ZHANG ; Guangping HUANG ; Xiaolong GU ; Chunmiao WANG ; Yan WANG ; Zhimin LU
The Korean Journal of Parasitology 2017;55(1):77-79
The infection by Limnodrilus hoffmeisteri Claparède, 1862 (Oligochaeta: Tubificinae) in humans is relatively uncommon. The present report is to describe an incidental human infection with oligochaetes in the nasal cavity of a Chinese man, a 25-year-old man residing in Zhangjiakou city, Hebei province, China presenting with nose bleed, severe itching, continuous sneezing, and rhinorrhea. A lot of oligochaete worms were found in the nasal discharge of the patient. The detected worms were identified as Limnodrilus hoffmeisteri (Annelida: Oligochaeta) based on morphological and molecular characteristics. This incidental L. hoffmeisteri nasal infection is the first case in China and indicates that oligochaete worms can be encountered in humans.
Adult
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Asian Continental Ancestry Group*
;
China
;
Epistaxis
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Humans
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Nasal Cavity*
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Pruritus
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Sneezing
9.Tree shrew umbilical cord mesenchymal stem cells:isolation, cultivation and osteogenic and adipogenic differentiation
Guangping RUAN ; Lu ZHU ; Jufen LIU ; Zian LI ; Jinxiang WANG ; Rongqing PANG ; Xinghua PAN
Chinese Journal of Tissue Engineering Research 2017;21(9):1373-1377
BACKGROUND: Studies have shown that umbilical cord mesenchymal stem cells are ideal seed cells for tissueengineering research.OBJECTIVE: To isolate, culture and identify tree shrew umbilical cord mesenchymal stem cells, in order toestablish a standardized tree shrew umbilical cord mesenchymal stem cell lines.METHODS: Caesarean-isolated tree shrew umbilical cord samples were used to isolate and culture umbilical cordmesenchymal stem cells using tissue explant adherent method. Flow cytometry assay was used to detect cellsurface markers. Osteogenic and adipogenic induction media were used to induce umbilical cord mesenchymalstem cells to differentiate into osteoblasts and adipocytes.RESULTS AND CONCLUSION: The cultured umbilical cord mesenchymal stem cells expressed CD90 and CD105 with the positive rate of 99.9% and 99.8% respectively. Hematopoietic stem cell marker CD34 expression ratewas 0.0% and the endothelial cell marker CD31 expression rate was 0.7%, in line with the characteristics of umbilicalcord mesenchymal stem cell surface markers. Calcium nodules by alizarin red staining and lipid droplets by oil red Ostaining were observed in the induced cells. These experimental findings indicated that umbilical cord mesenchymalstem cells from tree shrews capable of osteogenic and adipogenic differentiation were successfully isolated and cultured.
10.Effects of liraglutide on eNOS and IRS-1 expressions in human umbilical vein endothelial cells cultured with high glucose
Ling YUE ; Jing DONG ; Guangda XIANG ; Linshuang ZHAO ; Junxia ZHANG ; Guangping ZHU ; Lin XIANG ; Min LIU ; Junyan LU
Chinese Journal of Endocrinology and Metabolism 2016;32(4):327-329
Humanumbilicalveinendothelialcells(HUVECs)weretreatedwith3nmol/Lliraglutidefor10, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, and 270 minutes at the concentrations of 5. 5 or 30 mmol/L glucose. Western blot analysis was used to detected protein expression and phosphorylation of insulin receptor substrates-1 ( IRS-1 ) and endothelial nitric oxide synthase ( eNOS ) . The results showed that the baseline level of phosphorylated-eNOS/eNOS was lower in high glucose group than that in normal group(0. 239 ± 0. 016 vs 0. 400 ± 0. 02,P<0. 05). Liraglutide time-dependently increased phosphorylated-eNOS/eNOS and phosphorylated-IRS-1/IRS-1 levels at 5. 5 or 30 mmol/L glucose.

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