1.Non-suicidal self-injury behavior in adolescents: the impact of mobile phone social media dependence and related factors
Honghui WEI ; Ying ZHANG ; Ningning SUN ; Yue WANG ; Yang LI
Sichuan Mental Health 2025;38(3):211-216
BackgroundNon-suicidal self-injury (NSSI) behaviors are prevalent among adolescents, significantly affecting their physical and mental well-being. Understanding the risk factors associated with adolescent NSSI is crucial for prevention. Previous studies have identified mobile phone dependence as a risk factor for NSSI in adolescents. However, as a key form of mobile phone dependence, the evidence regarding the impact of mobile phone social media dependence on adolescent NSSI behavior remains insufficient. ObjectiveTo explore the impact of mobile phone social media dependence and its associated factors on adolescent NSSI behavior, so as to provide references for intervention strategies targeting NSSI in adolescents. MethodsA total of 100 adolescents diagnosed with NSSI according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), and receiving treatment at Tongde Hospital of Zhejiang Province from January 2022 to December 2023 were included in the study group. Concurrently, 100 age- and sex-matched students from Hangzhou were recruited as the control group. Assessments were conducted using Ottawa Self-injury Inventory(OSI) Function Subscale and Addiction Features Subscale, Adolescents Self-Harm Scale(ASHS), and Mobile Phone Social Media Dependence Questionnaire. Multiple linear regression was used to analyze the factors influencing NSSI behaviors. ResultsThe research group had a total of 99 patients (99.00%) who completed the study, while the control group consisted of 97 (97.00%) adolescents who finished this research.The study group had statistically significantly higher total scores on the Mobile Phone Social Media Dependence Questionnaire, as well as higher scores on the conflict and withdrawal dimensions, compared with control group(t=-3.061, -2.874, -2.368, P<0.05 or 0.01). The study group also scored significantly higher on the OSI Function Subscale for internal emotion regulation, social influence, external emotion regulation, and sensation-seeking factors, as well as on the OSI Addiction Features Subscale scores, compared to the control group(t=-22.249, -8.854, -17.968, -10.591, -20.157, P<0.01). OSI Function Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores (r=0.321, P<0.01), and OSI Addiction Features Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores (r=0.282, P<0.01). ASHS scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores (r=0.145, P<0.05). Multiple linear regression analysis showed that compulsivity (β=0.416, P<0.01) and conflict (β=0.256, P<0.05) were significant predictors for adolescent NSSI behaviors. ConclusionAdolescent NSSI behaviors are associated with mobile phone social media dependence. The compulsivity and conflict dimension of mobile phone social media dependence are influencing factors for adolescent NSSI behaviors. The higher level of the compulsivity and conflict are associated with an increased risk of the NSSI behaviors in adolescents. [Funde by Zhejiang Medical and Health Science and Technology Plan Project in 2022 (number, 2022KY704]
2.Tumor-intrinsic PRMT5 upregulates FGL1 via methylating TCF12 to inhibit CD8+ T-cell-mediated antitumor immunity in liver cancer.
Jiao SUN ; Hongfeng YUAN ; Linlin SUN ; Lina ZHAO ; Yufei WANG ; Chunyu HOU ; Huihui ZHANG ; Pan LV ; Guang YANG ; Ningning ZHANG ; Wei LU ; Xiaodong ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):188-204
Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8+ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8+ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.
3.A study on clinical manifestations and correlation of symptoms of traditional Chinese medicine in emigrated plateau population
Tiantian XIA ; Wei ZHOU ; Li TONG ; Pan SHEN ; Ningning WANG ; Nan ZHANG ; Zhexin NI ; Yue GAO
Military Medical Sciences 2025;49(8):610-616
Objective To investigate the clinical manifestations of traditional Chinese medicine(TCM)and their associations with TCM constitutions in individuals who have migrated to plateau areas,and to provide a scientific basis for plateau health management.Methods Migrants living in areas above 3000 m were selected as research subjects.Data were collected by using TCM symptom assessment scales and constitution assessment scales.Descriptive statistical analysis was conducted to determine the incidence and severity of symptoms among individuals with different migration durations,and core symptoms were identified.Factor analysis was performed by using SPSS software to extract symptom clusters and explore the correlation between core symptoms and TCM constitutions.Results Among individuals who migrated to plateau areas,the incidence of discomfort symptoms was 83.44%.The five most common symptoms were dry skin(67.94%),forgetfulness(56.03%),dry mouth(52.06%),yellow urine(48.73%),and insomnia(47.14%).In the top 10 symptoms with the highest increase in incidence,yellow urine(33.51%)and forgetfulness(26.33%)were both present in the top 10 symptoms across different migration durations.Factor analysis extracted 5,2,4,and 6 symptom clusters from the overall population,individuals who migrated within 1 year,those who migrated for 1-2 years,and those who migrated over 2 years,respectively.Qi-deficiency constitution(QDC),blood stasis constitution(BSC),qi stagnation constitution(QSC),phlegm-dampness constitution(PDC),and dampness-heat constitution(DHC)were significantly positively correlated with forgetfulness.Conclusion Migrating to plateau areas can induce discomfort symptoms,and both the number and incidence of symptoms increase with longer migration durations.The number and incidence of high-frequency symptoms(incidence≥30%)increase with prolonged migration time.There are differences in the composition and severity of symptom clusters across different migration durations.QDC,BSC,QSC,PDC,and DHC are closely related to forgetfulness and can be considered risk constitutions for forgetfulness.Timely attention to changes in symptom clusters and constitutions can help prevent and mitigate the occurrence and development of symptoms.
4.A study of suctioning flexible ureteroscopy with intelligent pressure-control in treating patients with urogenic sepsis after drainage at different times
Wei MENG ; Feng LYU ; Huajun ZHANG ; Bo CHEN ; Shuaijiang LU ; Ningning LI ; Bo CAI ; Limin MA ; Yangbo GUAN
Journal of Modern Urology 2024;29(2):126-129
【Objective】 To investigate the safety and effectiveness of suctioning flexible ureteroscopy with intelligent pressure-control at different times after drainage for patients with urogenic sepsis complicated with upper urinary tract stones. 【Methods】 Clinical data of 59 patients treated in the Department of Urology, Affiliated Hospital of Nantong University during May 2022 and May 2023 were collected.The patients were divided into early lithotripsy (≤1 week) group (n=27) and late lithotripsy (>1 week) group (n=32).Baseline data, imaging data and postoperative data of the two groups were compared. 【Results】 There were no significant differences between the two groups in the stone-free rate, total incidence of complications, incidence of high-grade complications, length of stay after lithotripsy, hospitalization costs after lithotripsy and total hospitalization costs (P>0.05). 【Conclusion】 Both early lithotripsy (<1 week) and late lithotripsy (>1 week) are safe and effective in the treatment of urogenic sepsis after drainage.
5.Diagnostic value of cervical cell DNA ploidy analysis combined with B7-H4 and PKCδ for cervical cancer
Ningning ZHANG ; Zhe YANG ; Limei TAN ; Zhenning LI ; Di WANG ; Yongzhi WEI
Journal of International Oncology 2024;51(5):286-291
Objective:To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 (B7-H4) and protein kinase Cδ (PKCδ) for cervical cancer.Methods:A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime, 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results, they were divided into normal or inflammatory group ( n=52), low-grade cervical intraepithelial neoplasia (CIN) group ( n=68) and high-grade CIN group ( n=40). The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic (ROC) curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results:The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were 16 (30.8%), 27 (39.7%), 26 (65.0%) and 127 (79.4%), respectively, with a statistically significant difference ( H=55.86, P<0.001). Further pin-by-pair comparison showed that compared with normal or inflammatory groups, the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher (both P<0.05). The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group ( P<0.05). Serum B7-H4 levels in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were (57.21±10.21), (79.17±11.34), (92.73±15.36), (126.56±20.25) ng/ml, respectively, with a statistically significant difference ( F=285.45, P<0.001). Serum PKCδ levels were (89.34±18.29), (71.79±15.82), (53.39±11.84), (40.23±10.21) ng/ml, respectively, with a statistically significant difference ( F=216.28, P<0.001). Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups, low-grade CIN group, high-grade CIN group and cervical cancer group increased in turn (all P<0.05). Serum PKCδ levels in normal or inflammatory groups, high-grade CIN group and cervical cancer group were decreased in turn (all P<0.05). Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated ( r=-0.47, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 (95% CI: 0.78-0.86), and the sensitivity and specificity were 83.9% and 79.9%, respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 95.7% and 76.1%, respectively, and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 85.6% and 88.9%, respectively, and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 (95% CI: 0.97-0.99), and the sensitivity and specificity were 98.3% and 75.9%, respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy ( Z=8.00, P<0.001), serum B7-H4 ( Z=4.34, P<0.001), and serum PKCδ ( Z=4.61, P<0.001) alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum ( OR=2.94, 95% CI: 1.78-4.84, P<0.001), low level of PKCδ ( OR=4.33, 95% CI: 1.88-10.00, P=0.001) and positive DNA ploidy in cervical cells ( OR=5.77, 95% CI: 2.38-13.99, P<0.001) were independent risk factors for cervical cancer. Conclusion:The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased, the serum B7-H4 level is increased, the PKCδ level is decreased, and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.
6.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
7.Interaction between remimazolam and propofol for sedation during hysteroscopy
Leting JI ; Peipei HAO ; Ning DING ; Ningning DU ; Guangchao ZHU ; Changsheng LI ; Xiaoyong WEI
Chinese Journal of Anesthesiology 2024;44(2):204-208
Objective:To evaluate the interaction between remimazolam and propofol for sedation during hysteroscopy.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 20-45 yr, with body mass index of 18-28 kg/m 2, scheduled for elective hysteroscopy, were included. The test was conducted in two steps. Up-and-down sequential allocation was used to determine the median effective dose (ED 50) of remimazolam (group A) and propofol (group B). The ED 50 obtained in A and B groups were then used as the standard to determine the combination regimen in group C (0.25×ED 50 of remimazolam+ 0.75×ED 50 of propofol as the initial dose), in group D (0.5×ED 50 of remimazolam+ 0.5×ED 50 of propofol as the initial dose), and in group E (0.75×ED 50 of remimazolam+ 0.25×ED 50 of propofol as the initial dose). Up-and-down sequential allocation was used to determine the ED 50 of propofol when propofol and remimazolam were combined in C, D and E groups. The interaction between the sedative effects of two drugs was analyzed using the isobolographic analysis method, and the interaction coefficient and synergistic dose ratio of two drugs were calculated. Results:The ED 50 of remimazolam was 0.180 mg/kg in group A, and the ED 50 of propofol was 1.167 mg/kg in group B. The results of isobolographic analysis showed that remimazolam and propofol had a synergistic effect. When remimazolam 0.045, 0.090 and 0.135 mg/kg were combined with propofol 0.546, 0.288 and 0.160 mg/kg, the interaction coefficients were 1.393, 1.339 and 1.127 respectively. The synergistic dosage ratio of remimazolam and propofol was 1.0∶(3.2 to 12.0). Conclusions:Remimazolam and propofol have a synergistic effect on sedation when used for hysteroscopy, and the dose ratio is 1.0∶(3.2-12.0).
8.Modified YOLO-V5 model for identifying inflammatory bowel disease on CT enterography
Fujin WANG ; Mingzhu MENG ; Xin WANG ; Ningning WEI
Chinese Journal of Medical Imaging Technology 2024;40(10):1593-1598
Objective To investigate the value of modified YOLO-V5 model for identifying inflammatory bowel disease(IBD)displayed on CT enterography(CTE).Methods Totally 192 patients with IBD(103 cases of Crohn disease[CD subgroup]and 89 cases of ulcerative colitis[UC subgroup])and 103 patients with clinically suspected IBD but CTE showed no abnormality(no abnormality subgroup)were retrospectively collected as study group,while 5 patients with CD and 3 with UC were collected as test group.CTE images with diseased intestinal tubes present as thickened intestinal wall or no abnormality intestinal tubes were selected as data set(n=3 511).CTE in study group were divided into training set(n=3 160,including 1 063 from CD subgroup,931 from UC subgroup and 1 166 from no abnormality subgroup)and verification set(n=351,including 118 from CD subgroup,103 from UC subgroup and 130 from no abnormality subgroup)at the ratio of 9∶1,while 25 CET images(17 from 5 cases of CD and 8 from 3 cases of UC)in test group were used as test set.Diseased tubes of CD,UC and no abnormality tubes were labeled.Then 5 sub-models,including YOLO-V5n,YOLO-V5s,YOLO-V5m,YOLO-V5l and YOLO-V5x were constructed and trained with modified YOLO-V5,and their efficacy were verified in test set.Precision(Pr),recall(Rc)and mean average precision(mAP)were used to evaluate the efficacy of each sub-model for identifying IBD lesions displayed on CTE.Results The complexity of the above 5 sub-models increased successively.YOLO-V5l and YOLO-V5x sub-model had better diagnostic efficacy,the overall Pr,Rc,mAP_0.5 and mAP_0.5.0.95 of the former for identifying IBD lesions in training and validation sets was 0.97,0.93,0.96 and 0.91,while of the latter was 0.97,0.95,0.96 and 0.92,respectively.In test set,the efficacy of YOLO-V5n sub-model for identifying IBD lesions was low,with mAP_0.5∶0.95 of 0.66 and AUC of 0.82,whereas mAP_0.5∶0.95 of YOLO-V5x sub-model for identifying CD was as high as 0.92,and of YOLO-V5l sub-model for identifying UC was as high as 0.91.Conclusion YOLO-V5l and YOLO-V5x sub-models based on modified YOLO-V5 could effectively identify IBD lesions displayed on CTE.
9.Effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer evaluated as indeterminate response after surgery
Ningning ZHAO ; Zhuanzhuan MU ; Wenting GUO ; Xing WEI ; Yansong LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(12):736-740
Objective:To investigate the effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer (DTC) who were evaluated as indeterminate response (IDR) after surgery and before 131I therapy. Methods:A total of 281 DTC patients (89 males, 192 females, age (38.4±10.2)years ) assessed as IDR before 131I therapy and after total or near-total thyroidectomy in the Department of Nuclear Medicine of Peking Union Medical College Hospital from April 2009 to March 2022 were retrospectively analyzed. Patients were divided into 131I therapy group ( 131I group) and just thyroid stimulating hormone (TSH) suppressive therapy group (TSH group) according to whether receiving 131I therapy, and the efficacies of two groups at the end of follow-up were compared. Subgroup analysis was conducted in different risk stratifications (low-risk, moderate-risk and high-risk), positive thyroglobulin antibody (TgAb) group (TgAb≥115 kU/L) and negative TgAb group (TgAb<115 kU/L). For patients with positive TgAb, the duration and rate for TgAb declining to negative level under the 2 regimens were compared. Independent-sample t test, Mann-Whitney U test, χ2 test and Fisher exact test were performed to compare the differences between groups. Results:Median follow-up time was 39(6-146) months. There was no statistical difference between patients in 131I group and TSH group in baseline characteristics, and the efficacies at the end of follow-up was similar between the 2 groups ( χ2=6.50, P=0.075). For low-, moderate- and high-risk stratification, there were also no statistical differences of response to 2 regimens ( P=0.221; χ2=4.21, P=0.223; χ2=3.01, P=0.274). Similar results were showed for patients with positive and negative TgAb ( n=50, n=231; χ2=4.02, P=0.242; χ2=3.14, P=0.341). For patients with positive TgAb, the duration and rate for TgAb declining to negative level were not statistically different either between 2 regimens (71.0%(22/31) vs 14/19, χ2=0.04, P=0.836; 7.0(5.0, 9.3) vs 7.0(5.0, 7.3) months, z=-0.89, P=0.375). Conclusion:For DTC patients assessed as IDR after surgery, 131I therapy may not provide more benefit than follow-up with TSH suppressive therapy.
10.Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation
Ningning WANG ; Entao LI ; Huifang DENG ; Lanxin YUE ; Lei ZHOU ; Rina SU ; Baokun HE ; Chengcai LAI ; Gaofu LI ; Yuwei GAO ; Wei ZHOU ; Yue GAO
Journal of Pharmaceutical Analysis 2023;13(1):11-23
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Gluco-corticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by mul-tiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

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