1.A Single-cell Transcriptomic Study of Wenyang Jiedu Granules in Alleviating Influenza Virus Pneumonia by Suppressing Interferon Responses and Apoptotic Pathways in AT1 Cells
Jingyan XIN ; Shengle QIN ; Taoyu CHEN ; Yuntao LIU ; Xiaolu WANG ; Chaofeng LIANG ; Zhongde ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):76-85
ObjectiveTo investigate the molecular mechanisms by which Wenyang Jiedu granules (WYJD) alleviate influenza A virus (IAV)-induced pneumonia based on single-cell transcriptome sequencing. MethodsThirty female BALB/c mice were randomly divided into a blank control group (Control), IAV group, and WYJD low-, medium-, and high-dose groups (WYJD-L, WYJD-M, WYJD-H; 2.925, 5.85, 11.7 g·kg-1, n=6). Except for the Control group, all other groups were intranasally inoculated with IAV subtype H1N1 (A/PR/8/34) to establish an infection model. Two hours after modeling, drug administration was initiated and continued for 5 consecutive days, with daily monitoring of body weight and general condition. On day 6, mice were sacrificed and samples were collected. Lung index was calculated, and histopathological examination of lung tissue was performed. Lung tissues from the Control, IAV, and WYJD-H groups were subjected to single-cell transcriptome sequencing (n=3), focusing on type I alveolar epithelial cells (AT1) to analyze changes in gene expression and signaling pathways. Western blot was used to detect the expression changes of relevant proteins to validate the single-cell sequencing results. ResultsCompared with the Control group, the IAV group exhibited significantly decreased body weight (P<0.05) and significantly increased lung index (P<0.05). Compared with the IAV group, all WYJD-treated groups exhibited significantly increased body weight (P<0.01) and significantly decreased lung index (P<0.01). Single-cell sequencing analysis revealed that WYJD inhibited overactivation of interferon and inflammatory signaling pathways in AT1 cells after IAV infection, including interferon-γ response, interferon-α response, tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), and interleukin-6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) pathways. Compared with the Control group, the number of AT1 cells in the IAV group showed a decreasing trend. Compared with the IAV group, the WYJD-H group showed an increasing trend, although neither difference was statistically significant. Further analysis of AT1 cell subpopulation gene expression showed that, compared with the Control group, the IAV group exhibited increased expression of pro-apoptotic genes FAS cell surface death receptor (FAS) and cyclin-dependent kinase inhibitor 1A (CDKN1A), a significant increase in tumor protein p53 (Tp53) expression (P<0.05), and significant decreases in expression of the AT1 marker gene advanced glycosylation end-product-specific receptor (AGER) and membrane structural gene caveolin1 (CAV1) (P<0.05, P<0.01). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of FAS, CDKN1A, and Tp53 (P<0.05, P<0.01), and significantly increased expression of AGER and CAV1 (P<0.05, P<0.01). Regarding interferon response-related genes, compared with the Control group, the IAV group showed increased expression of interferon-stimulated gene 15 (ISG15), interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), signal transducer and activator of transcription 2 (STAT2), bone marrow stromal cell antigen 2 (BST2), and C-X-C motif chemokine ligand 10 (CXCL10), with a significant increase in 2′,5′-oligoadenylate synthetase-like protein 1 (OASL1) (P<0.05). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of all the above genes, with highly significant differences for ISG15, IFIT3, STAT2, BST2, and OASL1 (P<0.01), and a significant difference for CXCL10 (P<0.05). Among inflammation-related genes, compared with the Control group, the IAV group showed significantly increased expression of intercellular adhesion molecule 1 (ICAM1), tumor necrosis factor alpha-induced protein 3 (TNFAIP3), keratin 8 (KRT8), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), and TNFRSF1B (P<0.01), and increased expression of NFKBIA, a negative regulator of NF-κB (P<0.05). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of KRT8 and TNFRSF1B (P<0.05), while ICAM1, NFKBIA, TNFAIP3, and TNFRSF1A showed decreasing trends without statistical significance. Western blot validation showed that, compared with the Control group, protein expression levels of ISG15, FAS, p53, and phosphorylated p65 (p-p65) in lung tissue of the IAV group were significantly increased (P<0.05, P<0.01). Compared with the IAV group, the WYJD-H group showed significantly decreased expression of these proteins (P<0.05, P<0.01). ConclusionWYJD may alleviate viral pneumonia by targeting gene expression in AT1 cells, inhibiting overactivated interferon and inflammatory signaling pathways after IAV infection, and downregulating pro-apoptotic signaling, thereby reducing alveolar epithelial injury.
2.Analysis of plasma metabonomic characteristics of type 2 diabetes mellitus patients with turbid toxin accumulation syndrome
Ziqi ZHAO ; Pai PANG ; Yue REN ; Bin WANG ; Yuntao MA ; Qianjing YANG ; Shentao WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):34-42
Objective:
To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome.
Methods:
One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website.
Results:
There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways.
Conclusion
Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.
3.Role and mechanism of hypoxia-inducible factor 1 alpha regulating bone homeostasis in oral and maxillofacial diseases
Zeming LI ; Yuntao ZHANG ; Maolin WANG ; Yudong HOU
Chinese Journal of Tissue Engineering Research 2025;29(26):5680-5687
BACKGROUND:More and more scholars are investigating the mechanism of hypoxia-inducible factor-1α in regulating bone homeostasis and oral and maxillofacial diseases to provide new targets and strategies for the treatment of related disorders,but there is no relevant review.OBJECTIVE:To summarize the regulatory potential of hypoxia-inducible factor-1α in a variety of oral and maxillofacial diseases and bone homeostasis with the aim of providing a new research direction for oral and maxillofacial bone tissue engineering.METHODS:A literature review was conducted in databases such as PubMed,Web of Science and CNKI,for articles Published from 2003 to 2024.The keywords were"hypoxia inducible factor-1α,oral cavity,bone formation,osteoclast,angiogenesis,oxidative stress,tissue engineering,periodontitis,pulpitis,temporomandibular joint osteoarthritis"in Chinese and English.Finally,84 articles were included for review.RESULTS AND CONCLUSION:(1)Hypoxia-inducible factor-1α is essential in promoting bone tissue regeneration,facilitating osteogenic-angiogenic coupling,and mitigating damage from oxidative stress in bone tissue.(2)Increasing levels of hypoxia-inducible factor-1α in tissue cells reduces inflammation in periodontitis and promotes periodontal tissue remodeling,pulp regeneration,and involves in joint remodeling after temporomandibular joint osteoarthritis.(3)By stabilizing the level of hypoxia-inducible factor-1α in tissue cells,the micronutrient-carrying biomaterial promotes bone marrow mesenchymal stem cells to migrate and attach to the bone defect area,coupling angiogenesis and osteogenesis to achieve bone regeneration.(4)How to increase the level of hypoxia-inducible factor-1α in oral and maxillofacial tissues using bioactive materials to achieve bone regeneration at maxillofacial bone defects remains to be investigated.
4.The effect of cumulative non-high density lipoprotein cholesterol/high density lipo-protein cholesterol exposure on atherosclerotic cardiovascular disease
Luqing LIU ; Meixiao WANG ; Shihe LIU ; Xiaoxue ZHANG ; Yixiu CHEN ; Zhihui LIU ; Shouling WU ; Yuntao WU
Chinese Journal of Arteriosclerosis 2025;33(1):58-67
Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49%,8.71%,10.86%and 14.85%,respectively(Log-rank P<0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95%CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03~1.24),1.18(1.07~1.29),1.22(1.12~1.34),respectively;the HR(95%CI)of myocardial infarction were 1.15(0.87~1.53),1.44(1.10~1.88),1.67(1.29~2.17),respectively;the HR(95%CI)of revascularization were 1.21(0.99~1.49),1.31(1.07~1.60)and 1.49(1.22~1.81),respectively;the HR(95%CI)of ischemic stroke were 1.17(1.03~1.32),1.17(1.04~1.33)and 1.21(1.06~1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.
5.Role and mechanism of hypoxia-inducible factor 1 alpha regulating bone homeostasis in oral and maxillofacial diseases
Zeming LI ; Yuntao ZHANG ; Maolin WANG ; Yudong HOU
Chinese Journal of Tissue Engineering Research 2025;29(26):5680-5687
BACKGROUND:More and more scholars are investigating the mechanism of hypoxia-inducible factor-1α in regulating bone homeostasis and oral and maxillofacial diseases to provide new targets and strategies for the treatment of related disorders,but there is no relevant review.OBJECTIVE:To summarize the regulatory potential of hypoxia-inducible factor-1α in a variety of oral and maxillofacial diseases and bone homeostasis with the aim of providing a new research direction for oral and maxillofacial bone tissue engineering.METHODS:A literature review was conducted in databases such as PubMed,Web of Science and CNKI,for articles Published from 2003 to 2024.The keywords were"hypoxia inducible factor-1α,oral cavity,bone formation,osteoclast,angiogenesis,oxidative stress,tissue engineering,periodontitis,pulpitis,temporomandibular joint osteoarthritis"in Chinese and English.Finally,84 articles were included for review.RESULTS AND CONCLUSION:(1)Hypoxia-inducible factor-1α is essential in promoting bone tissue regeneration,facilitating osteogenic-angiogenic coupling,and mitigating damage from oxidative stress in bone tissue.(2)Increasing levels of hypoxia-inducible factor-1α in tissue cells reduces inflammation in periodontitis and promotes periodontal tissue remodeling,pulp regeneration,and involves in joint remodeling after temporomandibular joint osteoarthritis.(3)By stabilizing the level of hypoxia-inducible factor-1α in tissue cells,the micronutrient-carrying biomaterial promotes bone marrow mesenchymal stem cells to migrate and attach to the bone defect area,coupling angiogenesis and osteogenesis to achieve bone regeneration.(4)How to increase the level of hypoxia-inducible factor-1α in oral and maxillofacial tissues using bioactive materials to achieve bone regeneration at maxillofacial bone defects remains to be investigated.
6.Prediction of very early recurrence of pancreatic head cancer after radical surgery by preoperative enhanced CT imaging features and postoperative pathology
Yuan LI ; Weijun QI ; Yuntao BING ; Hangyan WANG ; Lei LI ; Chaolai MA ; Chunhui YUAN ; Dianrong XIU
Chinese Journal of General Surgery 2025;40(9):700-705
Objective:To predict very early recurrence after radical resection in patients with pancreatic head cancer by combining preoperative enhanced CT imaging findings and clinicopathological features.Methods:The clinicopathological and preoperative enhanced CT imaging features of 241 patients who underwent radical pancreaticoduodenectomy at Peking University Third Hospital from Jan 2010 to Dec 2022 were retrospectively collected and analyzed.Results:Using recurrence within 3 months after surgery as the definition for very early recurrence, 49 out of 241 patients experienced very early recurrence. Multivariate analysis showed that preoperative BMI<18.5 kg/m2( P=0.040), rim enhancement( P=0.028), lymphovascular invasion( P<0.001), and poor tumor differentiation ( P=0.013) were independent risk factors for very early recurrence. Conclusion:Enhanced CT imaging features combined with clinicopathological characteristics can predict very early recurrence after resection of pancreatic head cancer.
7.5G Remote Robot-assisted Sleeve Gastrectomy:First Case Report
Xiaopeng WANG ; Yan WANG ; Yuntao MA
Chinese Journal of Minimally Invasive Surgery 2025;25(1):46-51
The article reported a case of 5G remote robot-assisted sleeve gastrectomy completed on December 14,2023,by using the Minimally Invasive Tumai Laparoscopic Surgical Robotic System(MT-1000)and a 5G signal network system in a dual-master-knife mode.The patient's platform was located in the operating room of the Gansu Provincial People's Hospital(GSPH),and the main manipulator's table was located in the operating room of the Lanzhou New District Branch of the Gansu Provincial People's Hospital(straight-line distance between the two being 75.6 km).The total duration of the surgery was 120 min,including 30 min of loading time and 90 min of robotic operation time.The average intraoperative network delay was(55.16±25.33)ms,and the packet loss rate was 0.01%-0.1%.No adverse network events such as network interruption occurred,and the surgery was completed successfully.
8.Characteristics of traditional Chinese medicine syndromes in patients with Chikungunya hemorrhagic fever:a cross-sectional study
Shiying LU ; Danwen ZHENG ; Xintian HONG ; Yuping LIU ; Guangzong LI ; Zhifeng HONG ; Jinghua YANG ; Yan ZHANG ; Banghan DING ; Yuntao LIU ; Yuanyuan WANG ; Xin YIN ; Jingwei SHUI ; Xiaofei FAN ; Hai LAN ; Zhongde ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(11):1531-1539
Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.
9.Risk factors of silicon oil dependent after pars plana vitrectomy in open globe injuries: Eye Injury Vitrectomy Study
Wan LU ; Kang FENG ; Qihua WANG ; Bingjie WANG ; Tong SUN ; Zhizhong MA ; Yuntao HU
Chinese Journal of Ocular Fundus Diseases 2025;41(4):277-281
Objective:To observe and preliminarily analyze the risk factors related to silicone oil dependence after pars plana vitrectomy (PPV) in open globe injuries (OGI) .Methods:A retrospective clinical study. This study included 211 patients with OGI who received PPV treatment from January 1, 2005 to December 31, 2016 in Eye Injury Vitrectomy Study database. Silicone oil dependence was defined as the intraocular pressure <10 mm Hg (1 mm Hg= 0.133 kPa) in silicone oil tamponade eye 6 months after PPV. The patient's age, intraocular pressure, type of injury, length of eyeball wound, as well as the presence of ciliary body injury, choroidal injury, and retinal resection and/or defect area were recorded in detail. Logistic multifactorial regression analyzed the correlation between age, eye wound length and ciliary body iinjury, choroidal injury and retinal resection and/or defect severity and silicone oil dependence.Results:211 OGI eyes underwent vitrectomy were included, the mean age of the study population was 32.93 years (range 1-73 years), and the median follow-up period was 20.06 months (range 5.85-90.58 months). Among the 211 eyes, 121 (57.3%, 121/211), 52 (24.6%, 52/211), 23 (10.9%, 23/211) and 15 (7.1%, 15/211) were rupture, perforation, intraocular foreign bodies and penetrating injury, respectively. 98 eyes (46.4%, 98/211) of silicone oil dependence in total, among them, 64 (65.3%, 64/98), 19 (19.4%, 19/98), 9 (9.2%, 9/98) and 6 (6.1%, 6/98) eyes were rupture, perforation, intraocular foreign body and penetrating injury, respectively. Correlation analysis revealed that silicone oil dependence was significantly associated with ciliary body injury [odds ratio ( OR) = 2.150, 95% confidence interval ( CI) 1.052-4.393], choroidal injury ( OR=3.233, 95% CI 1.454-7.191), and retinal injury ( OR=2.731, 95% CI 1.393-5.353). No correlation was found with age ( OR= 0.981, 95% CI 0.960-1.002) or ocular wound length ( OR=1.716, 95% CI 0.987-2.984) ( P> 0.05). Conclusion:Silicone oil dependency following PPV in OGIs are associated with ciliary body, choroidal, and retinal injuries, but no association with age or length of the ocular wound.
10.The effect of cumulative non-high density lipoprotein cholesterol/high density lipo-protein cholesterol exposure on atherosclerotic cardiovascular disease
Luqing LIU ; Meixiao WANG ; Shihe LIU ; Xiaoxue ZHANG ; Yixiu CHEN ; Zhihui LIU ; Shouling WU ; Yuntao WU
Chinese Journal of Arteriosclerosis 2025;33(1):58-67
Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49%,8.71%,10.86%and 14.85%,respectively(Log-rank P<0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95%CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03~1.24),1.18(1.07~1.29),1.22(1.12~1.34),respectively;the HR(95%CI)of myocardial infarction were 1.15(0.87~1.53),1.44(1.10~1.88),1.67(1.29~2.17),respectively;the HR(95%CI)of revascularization were 1.21(0.99~1.49),1.31(1.07~1.60)and 1.49(1.22~1.81),respectively;the HR(95%CI)of ischemic stroke were 1.17(1.03~1.32),1.17(1.04~1.33)and 1.21(1.06~1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.


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