1.Construction and Application of An Animal Model of Respiratory Syncytial Virus Infection Based on Humanized IGF1R Mice
Xiaowei YANG ; Dan XIE ; Shuran LI ; Lei BAO ; Zihan GENG ; Xian LIU ; Mengyao CUI ; Yaxin WANG ; Shan CAO ; Xiaolan CUI ; Jing SUN ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):48-53
ObjectiveTo construct an animal model of respiratory syncytial virus(RSV)-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect (CPE), and 50% tissue culture infective dose(TCID50) was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group, the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor (IGF1R) mice was evaluated by measuring organ indices, peripheral blood lymphocyte percentages, pulmonary pathology and imaging, and pulmonary viral load. Additionally, ten BALB/c mice served as normal group, and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group, ribavirin group (82.5 mg·kg-¹·d-¹), and high and low dose groups of Lianhua Qingwen (3.3 mg·kg-¹·d-¹ , 1.65 mg·kg-¹·d-¹), with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention, and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group, large solid and diffuse ground-glass shadows were seen, and the lung volume was significantly increased (P<0.01). The lung index was significantly increased (P<0.01), and both the spleen index and thymus index were significantly decreased (P<0.01). The percentages of CD3+ and CD4+T cells were significantly decreased (P<0.05), and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue, which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached, with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV, the expression of viral nucleic acids in the lung tissue of the mice was significantly increased, with significant differences compared with the normal group (P<0.01). The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced, with significant differences compared with the normal group (P<0.01). ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC, and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed, which is suitable for the evaluation of anti-RSV drugs.
2.Construction and Application of An Animal Model of Respiratory Syncytial Virus Infection Based on Humanized IGF1R Mice
Xiaowei YANG ; Dan XIE ; Shuran LI ; Lei BAO ; Zihan GENG ; Xian LIU ; Mengyao CUI ; Yaxin WANG ; Shan CAO ; Xiaolan CUI ; Jing SUN ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):48-53
ObjectiveTo construct an animal model of respiratory syncytial virus(RSV)-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect (CPE), and 50% tissue culture infective dose(TCID50) was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group, the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor (IGF1R) mice was evaluated by measuring organ indices, peripheral blood lymphocyte percentages, pulmonary pathology and imaging, and pulmonary viral load. Additionally, ten BALB/c mice served as normal group, and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group, ribavirin group (82.5 mg·kg-¹·d-¹), and high and low dose groups of Lianhua Qingwen (3.3 mg·kg-¹·d-¹ , 1.65 mg·kg-¹·d-¹), with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention, and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group, large solid and diffuse ground-glass shadows were seen, and the lung volume was significantly increased (P<0.01). The lung index was significantly increased (P<0.01), and both the spleen index and thymus index were significantly decreased (P<0.01). The percentages of CD3+ and CD4+T cells were significantly decreased (P<0.05), and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue, which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached, with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV, the expression of viral nucleic acids in the lung tissue of the mice was significantly increased, with significant differences compared with the normal group (P<0.01). The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced, with significant differences compared with the normal group (P<0.01). ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC, and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed, which is suitable for the evaluation of anti-RSV drugs.
3.Effect of Influenza A Virus on BEAS-2B in Human Lung Epithelial Cells and Intervention Effect of Shufeng Jiedu Capsule-containing Serum
Shan CAO ; Zihan GENG ; Lei BAO ; Yingli XU ; Bo PANG ; Jingsheng ZHANG ; Yu ZHANG ; Mengping CHEN ; Yaxin WANG ; Ronghua ZHAO ; Shanshan GUO ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):90-97
ObjectiveTo observe the effect of Shufeng Jiedu capsule (SFJD)-containing serum on human lung epithelial cells infected by influenza A virus, and investigate the protective effect of the drug on the cells and the potential antiviral effect. MethodThe SFJD-containing serum was prepared and used to treat human lung epithelial cells (BEAS-2B) cultured in vitro. The viability of cells treated with different concentrations of SFJD-containing serum was measured by the cell counting kit-8 (CCK-8), and the optimal concentration of SFJD-containing serum was screened for subsequent experiments. BEAS-2B cells were classified into normal control, virus infection, and SFJD-containing serum groups, and the CCK-8 method was used to detect the survival rate of BEAS-2B cells after virus infection and drug administration. The expression of influenza virus nucleic acid in the cells of each group was determined, and the apoptosis of cells in different groups was observed by fluorescence microscopy. Real-time PCR was employed to determine the mRNA levels of influenza virus nucleoprotein (NP), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88) in each group of cells. The immunofluorescence assay was used to detect the fluorescence intensities of TLR4, MyD88, and phosphorylated nuclear factor-κB (p-NF-κB) in lung epithelial cells. ResultCompared with that in the control group (normal serum), the cell survival rates in the blank serum and the SFJD-containing serum (5%, 10%, and 20%) groups were 100.00%±0.00%, 89.05%±4.80%, 87.13%±5.90%, 93.83%±6.03%, and 99.33%±3.39%, respectively (P<0.01). The SFJD-containing serum of 20% was selected as the optimal treatment for subsequent experiments. Compared with the normal control group, the virus infection group showed reduced cell survival rate (P<0.01), and the reduction was increased by the SFJD-containing serum (P<0.01). Compared with the virus infection group, SFJD-containing serum reduced the virus load (P<0.01) to decrease apoptosis. Compared with the normal control group, the virus infection group showed up-regulated mRNA levels of NP, TLR4, and MyD88 (P<0.01), and the up-regulation was down-regulated by the SFJD-containing serum (P<0.05, P<0.01). The fluorescence intensities of TLR4, MyD88, and p-NF-κB proteins in the cells increased after virus infection compared with those in the normal control (P<0.05, P<0.01), and they were decreased after administration with the SFJD-containing serum (P<0.05). ConclusionThe SFJD-containing serum can inhibit influenza virus in vitro by increasing the survival rate, reducing the apoptosis, and down-regulating the protein levels of TLR4, MyD88, and p-NF-κB in BEAS-2B cells.
4.Identification and anti-inflammatory activity of chemical constituents and a pair of new monoterpenoid enantiomers from the fruits of Litsea cubeba
Mei-lin LU ; Wan-feng HUANG ; Yu-ming HE ; Bao-lin WANG ; Fu-hong YUAN ; Ting ZHANG ; Qi-ming PAN ; Xin-ya XU ; Jia HE ; Shan HAN ; Qin-qin WANG ; Shi-lin YANG ; Hong-wei GAO
Acta Pharmaceutica Sinica 2024;59(5):1348-1356
Eighteen compounds were isolated from the methanol extract of the fruits of
5.Standardized operational protocol for the China Human Brain Bank Consortium(2nd edition)
Xue WANG ; Zhen CHEN ; Juan-Li WU ; Nai-Li WANG ; Di ZHANG ; Juan DU ; Liang YU ; Wan-Ru DUAN ; Peng-Hao LIU ; Han-Lin ZHANG ; Can HUANG ; Yue-Shan PIAO ; Ke-Qing ZHU ; Ai-Min BAO ; Jing ZHANG ; Yi SHEN ; Chao MA ; Wen-Ying QIU ; Xiao-Jing QIAN
Acta Anatomica Sinica 2024;55(6):734-745
Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.
6.Clinical characteristics and prognostic factors of 145 patients with drug-induced liver injury
Hongli DU ; Xu LI ; Xuechun SHAN ; Yunying HU ; Leilei BAO ; Hui WANG
Academic Journal of Naval Medical University 2024;45(10):1259-1265
Objective To explore the clinical characteristics of patients with drug-induced liver injury(DILI),so as to provide references for its diagnosis and treatment.Methods The clinical data of inpatients diagnosed as DILI in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University),from Jan.2017 to Dec.2021 were retrospectively analyzed,including basic information,underlying diseases,drug use history,clinical manifestations,laboratory indexes,severity and prognosis of DILI.Results Among 145 patients with DILI,112 cases(77.24%)were hepatocellular type,25 cases(17.24%)were cholestatic type,and 8 cases(5.52%)were mixed type.The types of drugs causing DILI mainly included traditional Chinese medicine,proprietary Chinese medicine and anti-infective drugs,and the proportions were 48.72%(76/156),16.03%(25/156),and 10.26%(16/156),respectively.The common clinical manifestations of DILI patients were jaundice(76.55%),poor appetite(52.41%),and fatigue(49.66%).The levels of alanine transaminase(ALT),aspartate transaminase,alkaline phosphatase(ALP),total bilirubin(TBil),γ-glutamyl transferase and albumin(ALB),as well as the length of hospital stay and severity distribution were significantly different among different types of liver injury(all P<0.05).The levels of ALT and ALB in the good prognosis group were significantly higher than those in the poor prognosis group,while the levels of TBil and international normalized ratio in the good prognosis group were significantly lower than those in the poor prognosis group(all P<0.05).Multivariate analysis showed that INR was an independent predictor of the prognosis of DILI(P<0.05).Conclusion Serum biochemistry indicators can help to identify the clinical classification and prognosis of DILI.Traditional Chinese medicine,proprietary Chinese medicine and other drugs can cause DILI.Medical staff should pay attention to it and strengthen public health education.
7.Efficacy and Mechanism of Lutongning Granules in Treatment of Trigeminal Neuralgia Induced by Injection of Talc into Infraorbital Foramen of Model Rats Based on P2X7R-mediated Neuroinflammation
Qiyue SUN ; Shuran LI ; Shuangrong GAO ; Shanshan GUO ; Zihan GENG ; Lei BAO ; Ronghua ZHAO ; Jingsheng ZHANG ; Bo PANG ; Yingli XU ; Yu ZHANG ; Shan CAO ; Yaxin WANG ; Xiaolan CUI ; Bing HAN ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):56-63
ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.
8.Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis
Bao YINI ; Shan QIYUAN ; Lu KEDA ; Yang QIAO ; Liang YING ; Kuang HAODAN ; Wang LU ; Hao MIN ; Peng MENGYUN ; Zhang SHUOSHENG ; Cao GANG
Journal of Pharmaceutical Analysis 2024;14(8):1099-1109
Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.
9.Sentinel surveillance data of influenza in Hunan Province from 2014 to 2023
Xiao-Lei WANG ; Chao-Yang HUANG ; Qian-Lai SUN ; Zhi-Hong DENG ; Yi-Wei HUANG ; Shan-Lu ZHAO ; Kai-Wei LUO ; Xiang REN ; Sheng-Bao CHEN ; Zhi-Hui DAI
Chinese Journal of Infection Control 2024;23(11):1413-1420
Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI%]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI%of 4.70%.ILI%among different years presented statistically significant differences(P<0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90%.The positive rate of influenza virus in ILI specimens was 14.14%,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P<0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People<15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).
10.Transcatheter edge-to-edge repair in acute mitral regurgitation following acute myocardial infarction:a case report
Tong KAN ; Xing-Hua SHAN ; Song-Hua LI ; Fei-Fei DONG ; Ke-Yu CHEN ; Hua WANG ; Rui BAO ; Sai-Nan GU ; Yong-Wen QIN ; Yuan BAI
Chinese Journal of Interventional Cardiology 2024;32(11):658-660
Acute mitral regurgitation(MR)in the setting of myocardial infarction(MI)may be the result of papillary muscle rupture(PMR).The clinical presentation can be catastrophic,with refractory cardiogenic shock.This condition is associated with high morbidity and mortality.Transcatheter edge-to-edge repair(TEER)has become increasingly common in treating severe mitral regurgitation.This case details a successful TEER is feasible and safe in patients with acute MR following MI.TEER is an emerging treatment option in this clinical scenario that should be taken into consideration.

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