1.Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy
Rui WANG ; Tiantian BAN ; Lihui XUE ; Xinyi FENG ; Jiyuan GUO ; Jiaqi LI ; Shenghe JIANG ; Xiaolei HAN ; Baofeng HU ; Wenli ZHANG ; Naijun WU ; Shuang LI ; Yajuan QI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):66-77
ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang (BWT) on non-alcoholic fatty liver disease (NAFLD) and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups: normal control, model, positive drug (pioglitazone hydrochloride 1.95×10-3 g·kg-1), and low-, medium-, and high-dose BWT (1.3,2.5 and 5.1 g·kg-1). Following a 12-week high-fat diet (HFD) inducement, the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week, glucose tolerance (GTT) and insulin tolerance (ITT) tests were conducted. Subsequently, the mice were euthanized for the collection of liver tissue and serum, and the subcutaneous adipose tissue (iWAT) and epididymal adipose tissue (eWAT) were weighed. Serum levels of total triglycerides (TG) and liver function indicators,such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. Histological examinations, including oil red O staining, hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy, were performed to evaluate hepatic lipid deposition, pathological morphology, and ultrastructural changes, respectively. Meanwhile, Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to analyze alterations, at both gene and protein levels, the insulin signaling pathway molecules, including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 (IRS1/2/Akt/FoxO1), glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase (Pepck) and glucose-6-phosphatase (G6Pase), lipid metabolism-related genes stearoyl-coA desaturase-1 (SCD-1) and carnitine palmitoyltransferase-1 (CPT-1), fibrosis-associated molecules α-smooth muscle actin (α-SMA), type Ⅰ collagen (CollagenⅠ), and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3(TGF-β1/p-Smad/Smad2/3), inflammatory factors such as interleukin(IL)-6, IL-8, IL-11, and IL-1β, autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1, and the expression of mammalian target of rapamycin (mTOR). ResultCompared with the model group, BWT reduced the body weight and liver weight of NAFLD mice(P<0.05, P<0.01), inhibited liver lipid accumulation, and reduced the weight of white fat: it reduced the weight of eWAT and iWAT(P<0.05, P<0.01) as well as the serum TG content(P<0.05, P<0.01). BWT improved the liver function as reflected by the reduced ALT and AST content(P<0.05, P<0.01). It improved liver insulin resistance by upregulating IRS2, p-Akt/Akt, p-FoxO1/FoxO1 expressions(P<0.05). Besides, it improved glucose and lipid metabolism disorders: it reduced fasting blood glucose and postprandial blood glucose(P<0.05, P<0.01), improved GTT and ITT(P<0.05, P<0.01), reduced the expression of Pepck, G6Pase, and SCD-1(P<0.01), and increased the expression of CPT-1(P<0.01). The expressions of α-SMA, Collagen1, and TGF-β1 proteins were down-regulated(P<0.05, P<0.01), while the expression of p-Smad/Smad2/3 was downregulated(P<0.05), suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6, IL-8, IL-11 and IL-1β(P<0.01) and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression(P<0.05)while downregulating the expression of p62/SQSTM1 and mTOR(P<0.05). ConclusionBWT ameliorates NAFLD by multifaceted improvements, including improving IR and glucose and lipid metabolism, anti-inflammation, anti-fibrosis, and enhancing autophagy. In particular, BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.
2.Expert consensus on the evaluation and management of dysphagia after oral and maxillofacial tumor surgery
Xiaoying LI ; Moyi SUN ; Wei GUO ; Guiqing LIAO ; Zhangui TANG ; Longjiang LI ; Wei RAN ; Guoxin REN ; Zhijun SUN ; Jian MENG ; Shaoyan LIU ; Wei SHANG ; Jie ZHANG ; Yue HE ; Chunjie LI ; Kai YANG ; Zhongcheng GONG ; Jichen LI ; Qing XI ; Gang LI ; Bing HAN ; Yanping CHEN ; Qun'an CHANG ; Yadong WU ; Huaming MAI ; Jie ZHANG ; Weidong LENG ; Lingyun XIA ; Wei WU ; Xiangming YANG ; Chunyi ZHANG ; Fan YANG ; Yanping WANG ; Tiantian CAO
Journal of Practical Stomatology 2024;40(1):5-14
Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.
3.Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice
FU XUFENG ; HAN HANG ; YANG HONG ; XU BO ; DAI WENJIE ; LIU LING ; HE TIANTIAN ; DU XING ; PEI XIUYING
Journal of Zhejiang University. Science. B 2024;25(4):307-323,中插1-中插15
Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.
4.Honokiol,an SIRT3 activator,alleviates postoperative cognitive dysfunc-tion via inhibiting hippocampal neuronal ferroptosis in mice
Tao HUANG ; Tiantian HAN ; Qianqian XU ; Zhen ZHANG ; Pengchao HU ; Xudong DING ; Huiyu LUO ; Lian ZENG
Chinese Journal of Pathophysiology 2024;40(5):827-835
AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.
5.Prevention effect of ceftriaxone sodium combined with bundle management on early ventilator-associated pneumonia
Yin HE ; Tiantian GAI ; Zunhai HAN
China Pharmacist 2024;27(6):1028-1033
Objective To observe the preventive effect of ceftriaxone sodium(CRO)combined with bundle management(BM)on early ventilator-associated pneumonia(VAP)in the intensive care unit(ICU)patients with mechanical ventilation(MV).Methods A total of 138 ICU patients treated with MV at Beijing Tongren Hospital affiliated to Capital Medical University were selected from May 2022 to April 2023.According to whether CRO was used,they were divided into CRO group and non-CRO(NCRO)group,and BM was performed during hospitalization in both groups.The incidence of early VAP,mortality,duration of mechanical ventilation,ICU stay,and total hospital stay were observed and compared between the two groups.In addition,the changes in inflammatory indicators[C-reactive protein(CRP),procalcitonin(PCT),and white blood cell count(WBC)]were compared before and after the intervention(on day 7).Results The incidence of early VAP was lower in the CRO group than in the NCRO group(P<0.05).The mortality rate of patients in the CRO group was lower than that in the NCRO group,but the difference was not statistically significant(P>0.05).The duration of mechanical ventilation,length of ICU stay and total hospital stay in the CRO group were shorter than those in the NCRO group(P<0.05).Before treatment,the CRP levels,serum PCT levels,and WBC were not significantly different between the two groups(P>0.05).Compared with before treatment,serum CRP levels,PCT levels and WBC were significantly decreased in the CRO and NCRO groups(P<0.05).In addition,serum CRP,PCT and WBC of the CRO group were lower than the NCRO group on the seventh day,with a statistically significant difference(P<0.05).Conclusion CRO combined with BM can reduce the incidence of early VAP in ICU patients undergoing MV,shorten MV time,ICU stay and total hospital stay,and reduce the level of inflammatory response.
6.The application and progress of machine learning and image recognition in predicting the prognosis of macular hiatus surgery
Tiantian CHENG ; Ruoan HAN ; Youxin CHEN
Journal of Chinese Physician 2024;26(5):656-662
Macular hiatus (MH) is a neuroepithelial deficiency that occurs in the macular area and can lead to severe central visual impairment. According to the different causes and stages of MH, clinical methods mainly include vitrectomy, inner limiting membrane dissection, and intraocular gas filling to achieve anatomical and functional recovery. The preoperative optical coherence tomography (OCT) parameters such as hole diameter, macular hole index, hole formation factor, and macular closure index, as well as patient baseline characteristics, are closely related to the prognosis of MH surgery. Artificial intelligence models based on machine learning and image recognition have shown potential in predicting surgical outcomes. This article aims to summarize the important parameters that affect the prognosis of MH surgery, analyze the current application status and possible improvement directions of machine learning and image recognition in MH surgery prediction, and provide a basis and new ideas for related research and clinical applications.
7.Effect of Different Noise Index and Adaptive Statistical Interactive Reconstruction-Veo Selection on Double Energy CT
Han ZHANG ; Tiantian YIN ; Qiushi YANG ; Zeguo WANG ; Heli HAN ; Wanjiang YU
Chinese Journal of Medical Imaging 2024;32(10):1069-1074
Purpose Based on European lumbar spine phantom,to investigate the effect of different noise index(NI)combined with adaptive statistical interactive reconstruction-veo(ASiR-V)weights on the measurement of lumbar spine bone density,and to explore the optimal combination of the two parameters.Materials and Methods Using GE Revolution CT spectral imaging scanning,54 groups of scanning parameters with NI values of 4-20(interval 2)combined with ASiR-V weights of 0-100%(interval 20%)were selected for spectral scanning of European lumbar spine phantom.Regions of interest were placed in the middle of L1,L2 and L3,respectively.hydroxyapatite(HAP)-H2O based substances were selected to measure the HAP content of each vertebral body.The differences between the measured bone density value and the true value under different NI combined with different ASiR-V were compared to evaluate its accuracy.Results There were statistically significant differences in HAP measurements of L1,L2 and L3 vertebra in 54 groups of scanning conditions(all P<0.001).When NI=14,ASiR-V80%;NI=16,ASiR-V100%;NI=18,ASiR-V60%;NI=18,ASiR-V80%;NI=20,ASiR-V60%;NI=20,ASiR-V80%;NI=20,ASiR-V100%,there was no statistically significant difference between HAP measured value and true body model value(P>0.05).Conclusion With NI=18,ASiR-V60%,spectral CT can accurately measure lumbar spine bone density and significantly reduce the radiation dose.In clinical application,bone density can be measured by low dose scanning by increasing the weight of NI and ASiR-V.
8.Correlation between cognitive impairment and cortical atrophy in elderly patients with asymptomatic carotid artery stenosis
Xiaokun YIN ; Jing YE ; Hailong YU ; Jing HANG ; Luhang TAO ; Chao JIANG ; Qian ZHANG ; Tiantian HAN ; Beilei CHEN
Chinese Journal of Health Management 2023;17(1):19-24
Objective:To analyze the correlation between cognitive impairment and cortical atrophy in elderly patients with asymptomatic carotid artery stenosis (ACAS).Methods:In this cross-sectional study, 40 consecutive elderly patients with ACAS treated in the Department of Neurology, Northern Jiangsu People′s Hospital from July 1, 2020 to June 30, 2021 (ACAS group), and 40 elderly healthy controls who accepted physical examination during the same period (control group) were included. Cognitive assessment was performed using the Mental State Examination Scale (MMSE) and the Montreal Cognitive Assessment Scale (MoCA), and brain magnetic resonance imaging scanning was performed in the ACAS group. The artificial intelligence technique was applied for brain lobe segmentation and cortical volume calculation. The χ2-test, independent sample t-test and Wilcoxon non-parametric test were used to analyze the difference of clinical data and cognitive scores between the two groups. In the ACAS group, the cortical volumes of the side with carotid stenosis was compared with that of the normal side, and Spearman′s correlation analysis was used to assess the correlation between cognitive scores and cortical atrophy. Results:Compared with the control group, the ACAS group got significantly lower scores of MMSE and MoCA, as well as lower scores of visuospatial executive function, attention and calculation, language function, abstraction ability and delayed recall [(25.60±2.49) vs (27.18±1.01), (22.05±3.59) vs (25.60±1.43), (2.73±1.04) vs (4.08±0.62), (4.53±0.93) vs (5.03±0.66), 2.00 (0.00) vs 3.00 (0.00), 1.00 (1.00) vs 2.00 (0.00), and (2.95±0.96) vs (3.35±0.62)] (all P<0.05). There was not significant differences in naming and orientation ability between the two groups (both P>0.05). The volume of cortical, temporal lobe, frontal lobe, parietal lobe and insular lobe on the side with carotid stenosis in the ACAS group were significantly smaller than those on the normal side [186.23 (177.97, 202.53) vs 194.67 (185.65, 204.82) cm 3, 54.74 (50.66, 56.95) vs 55.61 (51.24, 58.49) cm 3, 72.98 (70.76, 78.34) vs 75.27 (72.34, 80.66) cm 3, 53.66 (51.11, 57.86) vs 56.59 (52.80, 60.09) cm 3, 6.57 (6.35, 7.07) vs 6.72 (6.46, 7.34) cm 3] (all P<0.05). The MoCA score in the ACAS group was positively related to the cortical volume ratio of the two sides ( r=0.427, P<0.01). The attention ( r=0.353) and abstraction ( r=0.226) ability scores were positively correlated with the temporal lobe volume ratios of the two sides (both P<0.05). The visuospatial executive ( r=0.187) and language ( r=0.373) ability scores were positively correlated with frontal lobe volume ratios of the two sides (both P<0.05), and visuospatial executive ( r=0.386), naming ( r=0.344), language ( r=0.517), abstraction ( r=0.335) and delayed recall ( r=0.333) ability scores were positively correlated with parietal lobe volume ratios of the two sides (all P<0.05). Conclusion:In elderly patients with ACAS, the cognitive impairment and cortical atrophy on the sides with carotid stenosis are significant and a positive correlation is detected between them.
9.Construction and clinical empirical study of modular intervention for mechanical ventilation-dependent patients in ICU
Yin HE ; Zunhai HAN ; Tiantian GAI ; Zhenhui LU ; Ying YIN ; Ying SHI
Chinese Journal of Medical Physics 2023;40(12):1548-1553
Objective To explore the construction of modular intervention for patients dependent on mechanical ventilation in ICU,and to conduct the clinical empirical study.Methods A total of 100 mechanical ventilation-dependent patients in ICU were enrolled and divided into two groups according to the admission order,with 50 patients in each group.Control group received routine intervention,while observation group was treated with modular intervention in addition to the treatment given to control group.The weaning success rate,weaning time,complications,rehabilitation index,blood gas analysis index,psychological state,and nutritional status were compared between two groups.Results Compared with control group,observation group had higher weaning success rate,shorter weaning time,ICU stay and general ward admission,and lower incidence of complications(P<0.05).After intervention,observation group had lower PaCO2,and higher PaO2 and PaO2/FiO2 than control group(P<0.05);the scores of SAS,SDS and APACHEⅡwere lower in observation group than in control group(P<0.05);and the serum levels of ALB,PA,TRF and TP in observation group were higher than those in control group(P<0.05).Conclusion Modular intervention for mechanical ventilation-dependent patients in ICU can increase weaning success rate,improve blood gas analysis index and nutritional status,alleviate negative emotions,reduce complications and speed recovery.
10.E3 ubiquitin ligase alleviates DSS-induced colitis via regulating NLRP3 inflammasome activation
Tiantian TANG ; Wei HAN ; Ping LI ; Mengyi YANG ; Xiuqin FAN ; Rui WANG ; Kemin QI
Journal of Public Health and Preventive Medicine 2022;33(3):6-11
Objective To investigate the role of TRIM65 on DSS induced colitis and the underlying molecular mechanisms. Methods Trim65+/+ and Trim65-/- mice were administered with 3% (w/v) DSS in their drinking water for 5 consecutive days and then were switched to sterile water for 2 days. DSS treated mice were monitored daily for the clinical symptoms (bodyweight, stool consistency and rectal bleeding score). Mice were sacrificed on day 7 to measure colon length. Colon homogenates were collected to measure MPO activity and detect cleaved caspase-1 and mature IL-1β by Enzyme linked immunosorbent assay (ELISA) and Western blot. Trim65-/- mice were intraperitoneally injected with NLRP3 inflammasome inhibitor MCC950, and were given the above treatment to determine the effect of MCC950 on colitis in Trim65-/- mice. Results The results showed that deletion of Trim65 significantly enhanced weight loss and colon shortening in DSS mice, increased disease activity index and histopathological score, induced the activity of MPO, and promoted the F4/80+ immune cell infiltration, the activation of caspase-1 and the secretion of mature IL-1 in the colon of DSS mice. The NLRP3 inflammasome inhibitor MCC950 alleviated DSS induced colitis symptoms and inflammation levels in trim65 deficient mice. Conclusion TRIM65 plays an anti-inflammatory role in DSS induced colitis mice by inhibiting the activation of NLRP3 inflammasome.


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