1.Effects of Shenfuhuang Formula (参附黄配方) on Potential Targets of Action in the Brain Tissue of Sepsis Model Mice:Transcriptomics-Based Exploration
Yuchen WANG ; Xuerui WANG ; Xiaolong XU ; Jingxia ZHAO ; Jiabo WANG ; Yuan GAO ; Weijun KONG ; Qingquan LIU
Journal of Traditional Chinese Medicine 2025;66(1):65-70
ObjectiveTo investigate the possible mechanism of Shenfuhuang Formula (参附黄配方) in prevention and treatment of epsis-associated encephalopathy from the perspective of brain genomics. MethodsC57BL/6 mice were randomly divided into sham surgery group, sepsis group, and Shenfuhuang group, with 20 mice in each group. The sepsis group and Shenfuhuang group were induced to develop sepsis by cecal ligation and puncture (CLP) procedure. At 4 hours after modelling, Shenfuhuang group were gavaged with 2.5 g/(kg·d) of Shenfuhuang Formula, 0.5 ml each time, at 12 hours intervals, for a total of 4 times after modelling. Sepsis group and sham surgery group were given 0.5 ml of purified water orally. At 48 hours after modeling, the transcriptome sequencing was used to explore the differential gene expression in the effects of Shenfuhuang Formula on the brain regions of septic mice, and real-time PCR and ELISA were later used to further validate the differential gene and proteins expression. ResultsA total of 4605 genes were differentially expressed in Shenfuhuang group compared with sepsis group, of which 2353 genes were up-regulated and 2252 genes were down-regulated. According to the results of previous publications, six key genes were screened, including serine/threonine-protein kinase (Nek1), myelin-associated glycoprotein (Mag), endothelial cell-specific tyrosine kinase receptor (Tek), a disintegrin and metalloproteinase with thrombospondin motifs 20 (Adamts20), lymphocyte antigen 86 (Ly86), and E3 ubiquitin-protein ligase (Traip). Further genetic and protein validation revealed that, compared to the sham surgery group, the mRNA levels and corresponding protein levels of Nek1, Mag, Tek, Adamts20, Ly86, and Traip in the brain tissue of septic mice significantly reduced (P<0.05). In comparison to the sepsis group, Shenfuhuang group showed significantly increased mRNA levels and corresponding protein levels of Nek1, Mag, Tek, Adamts20, Ly86, and Traip (P<0.05). ConclusionThe potential therapeutic targets of Shenfuhuang Formula for treating sepsis-associated encephalopathy may be related to the Nek1, Mag, Tek, Adamts20, Ly86, and Traip genes and their encoded proteins.
2.Genomic characteristics and phylogenetic analyses of enteroaggregative Escherichia coli infection in diarrhea outpatients in Pudong New Area, Shanghai
Qiqi CUI ; Yuchen LU ; Suping WU ; Yinwen ZHANG ; Bing ZHAO ; Lifeng PAN ; Yingjie ZHENG ; Lipeng HAO
Shanghai Journal of Preventive Medicine 2025;37(4):342-349
ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.
3.Longitudinal associations between organophosphate esters exposure and blood pressure among school aged children in Beijing
Chinese Journal of School Health 2024;45(4):560-564
Objective:
To explore the longitudinal association between organophosphate esters (OPEs) exposure and blood pressure in children, so as to provide a reference for identifying the effects of OPEs exposure on child health.
Methods:
A total of 404 children from the Beijing Child Growth and Health Cohort (PROC) were enrolled using a case cohort study design, baseline physical examination, urine collection, questionnaires survey were administered in 2018 and follow up surveys in 2019-2020 and 2023. Participants were divided into case group ( n =140) and control group ( n =264) according to the observation of new onset of high blood pressure during the follow up period. High performance liquid chromatography tandem mass spectrometry was used to detect diethyl phosphate (DEP),bis (2-chloroethyl) phosphate (BCEP),bis (1-chloro-2-propyl) phosphate, (BCIPP), diphenyl phosphate(DPHP), dibutyl phosphate (DnBP), bis (1,3-dichloro-2-propyl) phosphate(BDCIPP), bis(2-butoxyethyl) phosphate(BBOEP), bis (2-butoxyethyl) 2-hydroxyethyl phosphate (BBOEHEP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP). Generalized linear mixed models and Quantile g computation models were developed to analyze the longitudinal associations between OPEs individual/mixed exposure and blood pressure in children.
Results:
The detection range of 9 OPEs metabolites,including DEP, BCEP, BCIPP, DPHP, DnBP, BDCIPP, BBOEP, BBOEHEP and 4-OH-TPHP at three time points (baseline, first follow up and second follow up) were 27.7%-92.1%, 24.0%-99.3% and 39.2%-90.9% respectively. Without adjustment for covariates such as gender, age, body mass index, Tanner stage, parental education, and monthly household income, and family history of hypertension, the increase of BDCIPP concentration and mixed exposure of OPEs may reduce children s systolic blood pressure( β= -0.85,-2.40,95%CI=-1.69--0.01,-3.30--1.50,P <0.05). After adjusting for the covariates, the longitudinal association of individual OPEs or mixed exposure with pediatric BP was not statistically significant ( P >0.05).
Conclusion
Children are commonly exposed to OPEs, and although no significant longitudinal associations are observed between exposure to OPEs and blood pressure among school aged children in Beijing, it is recommended that child exposure should be minimized whenever possible.
4.Evaluation of Juanbi Tongluo Oral Liquid on Improving Sciatic Neuronal Apoptosis in Type 2 Diabetic Model Mice
Fei HUANG ; Jiaxiang TONG ; Wei LIU ; Mengqiu LIU ; Ting CHEN ; Yuanjun LIU ; Mingying ZHANG ; Yuchen WU ; Wei WEI ; Yuting ZHAO ; Lie TIAN ; Yue ZHU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(9):932-940
OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.
5.One case of myelosuppression caused by pamiparib in combination with temozolomide in the treatment of small cell lung cancer
Yuchen YANG ; Yuting ZHAO ; Shiqi LI ; Jiayu GONG ; Riguga SU ; Yanyan SUN ; Zhihui CAI
Chinese Journal of Pharmacoepidemiology 2024;33(7):824-829
A 50-year-old male patient diagnosed with extensive stage small cell lung cancer was treated with pamiparib in combination with temozolomide.Five days later,the patient developed fever with fatigue.After 10 days,the patient stopped taking the drug due to worsening symptoms and was diagnosed with chemotherapy-induced myelosuppression(grade 4).The clinicist evaluated the patient's condition and assessed the association of adverse reactions using the Naranjo's evaluation scale,and concluded that myelosuppression may be induced by the combination of pamiparib and temozolomide.After symptomatic treatment,the patient's myelosuppression recovered completely.This article discusses the correlation between myelosuppression and the combination of the two drugs,provides treatment measures for this situation,briefly describes the risk factors of myelosuppression,treatment and prevention,and guides medical personnel to adjust the treatment plan in time according to different individuals in the process of using similar programs,and strengthens the monitoring and education of adverse drug reactions,so as to provide references for safe drug use.
6.Therapeutic Effect of Bushen Huoxue Prescription on Diuretic Resistance in Chronic Heart Failure
Yuchen SUN ; Yan ZHANG ; Wenhao YIN ; Shujun ZHAO ; Muchen ZHANG ; Guohua LIU ; Yaqin WANG ; Yilin ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):123-129
ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function, inflammation, and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups (39 cases). Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition, the observation group received Bushen Huoxue prescription. The cardiac function indicators, total response rate regarding symptom alleviation, exercise endurance, urine volume, body mass, quality of life, and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment, the two groups of patients showed no significant differences in terms of 24 h urine volume, body mass, 6 minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left ventricular ejection fraction (LVEF), stroke volume (SV), and serum levels of interleukin-6 (IL-6), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α). After treatment, the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association (NYHA) grading of cardiac function (P<0.05). After treatment, the body mass, MLHFQ score, and IL-6, TNF-α, and NT-proBNP levels decreased in both groups (P<0.05, P<0.01), and the observation group showed more significant decreases than the control group (P<0.05, P<0.01). Both groups showed increases in 24-h urine volume, 6MWT, LVEF, SV, and IL-4 after treatment (P<0.05, P<0.01), and the observation group showed more significant increases than the control group (P<0.05, P<0.01). ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover, it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.
7.Clinical Efficacy and Effect on Inflammatory Cytokines of Huangjin Shuangshen Jiawei Granules in Treating Patients with Postoperative Anxiety and Depression After PCI for Coronary Heart Disease
Muchen ZHANG ; Yuchen SUN ; Yaqin WANG ; Shujun ZHAO ; Sanchun TANG ; Ju YIN ; Yilin ZHAO ; Yan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):138-144
ObjectiveTo explore the clinical efficacy of Huangjin Shuangshen Jiawei (HJSSJW) granules in treating postoperative anxiety and depression after percutaneous coronary intervention (PCI) for coronary heart disease and the effects of this medicine on inflammatory cytokines. MethodNinety-four patients diagnosed with anxiety and depression after PCI were randomized into observation and control groups (47 cases) by the double-blind method. On the basis of conventional Western medical treatment, the observation group was treated with HJSSJW granules for 12 weeks, and the control group with the simulant of HJSSJW granules for 12 weeks. The two groups were compared in terms of Hamilton Anxiety and Depression Scales (HAMA-14, HAMD-24), Pittsburgh Sleep Quality Inventory (PSQI), Seattle Angina Score (SAQ), TCM symptom scores, traditional Chinese medicine (TCM) symptom score and response rate, serum levels of hypersensitive-C reactive protein (hs-CPR), tumor necrosis factor (TNF)-α, and interleukin (IL-6), and incidence of major adverse cardiovascular events (MACEs) and adverse reactions. ResultAfter treatment, both groups showed declined scores of HAMA-14, HAMD-24, and PSQI (P<0.05, P<0.01) and the observation group had lower scores of HAMA-14, HAMD-24, and PSQI than the control group (P<0.01). The scores of SAQ in both groups increased after treatment (P<0.01), and the observation group had higher score of each dimension than the control group (P<0.05). The TCM symptom scores decreased in both groups after treatment (P<0.01), and they were lower in the observation group than in the control group (P<0.05). The total response rate regarding TCM symptoms in the observation group was higher than that in the control group (χ2=9.225, P<0.01). After treatment, the levels of hs-CPR, IL-6, and TNF-α became lowered in both groups (P<0.01), and the observation group had lower levels of hs-CPR, IL-6, and TNF-α than the control group (P<0.05). The incidence of MACEs in the observation group was lower than that in the control group during the 90 d of the follow-up period (χ2=4.242, P<0.05). No adverse reactions associated with the use of HJSSJW granules were observed during the trial period. ConclusionHJSSJW granules can alleviate the bad mood, improve sleep, mitigate somatic symptoms, improve the quality of life, reduce inflammatory damage, and improve prognosis, being safe for clinical use in patients with postoperative anxiety and depression after PCI for coronary heart disease.
8.Consistency and difference analysis of ultrasound and dual-energy computed tomography in assessing gouty knee arthritis
Mengmeng YAN ; Meixia DU ; Lishan XIAO ; Yuchen LI ; Xiaoli LI ; Cheng ZHAO ; Chunping NING
Chinese Journal of Ultrasonography 2024;33(7):597-602
Objective:To assess the consistency of ultrasound and dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis(GA), reasons of the differences were further analyzed.Methods:The ultrasound and DECT images of 150 knee joints from 147 patients diagnosed with gout at the Gout Specialty Clinic of Qingdao University Affiliated Hospital from February 2022 to October 2023 were retrospectively analyzed. According to anatomy, the knee joint was anatomically segmented into five regions: intra-articular, anterior, posterior, medial, and lateral.Location of monosodium urate (MSU) deposition was meticulously recorded. The Kappa consistency test was employed to assess the consistency of the two examination results in different regions of the knee joint. The McNemar chi-square test was utilized to conduct a differential analysis between DECT and ultrasound results.Results:Double contour sign(DCS) (81.2%, 92/112) was the most common intra-articular ultrasound sign in knee joints with GA. In the extra-articular region, MSU was commonly deposited in and around the popliteal tendon (ultrasound: 51.6%, 66/128; DECT: 54.7%, 70/128). Corresponding MSU deposits on DECT were found in 9 of 92 joints with DCS and in 9 of 49 joints with aggregates detected on ultrasound.In the assessment of MSU deposits, ultrasound showed an overall higher positive rate than DECT (87.3% vs. 72.3%, P=0.001), with poor consistency between the two examinations (Kappa=0.153). In distinct anatomical regions, ultrasound and DECT showed high consistency in the medial (Kappa=0.697) and lateral (Kappa=0.718) sides and the difference was not statistically significant ( P>0.05). Intra-articular (Kappa=0.289) and anterior (Kappa=0.303) regions exhibited only fair consistency, with statistically significant diagnostic differences ( P<0.05). When exclusively assessing cases with tophus, ultrasound and DECT demonstrated high consistency in the medial and lateral aspects(Kappa=0.685, 0.748) without statistical difference ( P>0.05). In the anterior region, the consistency between the two examinations was moderate (Kappa=0.256), while in the intra-articular region, the consistency of the two methods was lower (Kappa=0.147), and the differences was statistically significant ( P<0.001). Conclusions:Both ultrasound and DECT exhibit good diagnostic capabilities for gouty knee arthritis.However, the consistency between the two techniques varies in different anatomical locations. Clinical assessment should be tailored based on the specific anatomical position. DECT has an advantage in evaluating intra-articular MSU deposits, while ultrasound is more sensitive to detect early and scattered MSU deposits.
9.Clinical value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System in differentiating thyroid follicular carcinoma and follicular adenoma
Lishan XIAO ; Yuchen LI ; Mengmeng YAN ; Meixia DU ; Cheng ZHAO ; Chunping NING
Chinese Journal of Ultrasonography 2024;33(9):791-799
Objective:To assess the discriminatory value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System (F-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and to compare its performance with other risk stratification systems(RSS).Methods:A retrospective analysis was conducted on 325 patients (327 thyroid nodules) diagnosed postoperatively as FTC or FTA at Affiliated Hospital of Qingdao University from January 2016 to December 2023. The cases were divided into FTC group (81 nodules) and FTA group (246 nodules). The nodules were classified based on F-TIRADS, the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS), the 2015 American Thyroid Association guidelines (ATA guidelines), and the 2017 European Thyroid Association Thyroid Imaging Reporting and Data System (EU-TIRADS) by two ultrasound physicians. Multivariate Logistic regression analysis was used to identify independent predictors associated with FTC. Diagnostic performance of the 4 RSS was compared using postoperative pathological results as the gold standard.Results:Multivariate Logistic regression analysis showed maximum diameter, solid composition, hypoechogenicity, unclear or angular margins, marginal or ring calcifications, trabecular structure, and central blood flow were independent predictors of FTC( OR=1.914, 3.427, 9.926, 9.163, 45.918, 3.191, 8.936, respectively; all P<0.05). Within each RSS, the actual malignancy rate increased with higher risk categories, aligning closely with the recommended malignancy rates (except for ATA guidelines). The optimal cut-off values for distinguishing FTC from FTA were FTC risk 50%-90% in F-TIRADS, C-TIRADS 4B, moderately suspicious nodules in ATA guidelines, and EU-TIRADS 4, with areas under the curve of 0.916, 0.808, 0.827, and 0.836, respectively. F-TIRADS demonstrated the best overall performance (sensitivity: 82.72%, specificity: 82.93%), with significant differences compared with C-TIRADS, ATA guidelines, and EU-TIRADS (all P<0.05). Conclusions:F-TIRADS is highly effective in distinguishing FTA from FTC, outperforming C-TIRADS, ATA Guidelines, and EU-TIRADS. Clinicians should pay close attention to solid hypoechoic nodules with unclear or angular margins, marginal or ring calcifications, central blood flow, or a trabecular structure.
10.Effect of medium and low doses X-ray irradiation on polarization type changes of tumor associated macrophages
Chaonan SUN ; Yuxin LIU ; Yunyun CHENG ; Yuchen WU ; Jiguo LIN ; Yuyao WANG ; Gang ZHAO
Chinese Journal of Immunology 2024;40(12):2465-2470,2477
Objective:To explore effects and mechanisms of medium and low doses X-ray irradiation on polarization type changes of tumor associated macrophages(TAMs).Methods:Mouse RAW264.7 macrophage line was cultured with supernatant of 4T1 tumor cell culture(4T1-TCS)of mouse breast cancer,and induced to M2 TAMs.On this basis,medium and low doses X-ray irra-diation was conducted,and NO was detected by Griess method,CD86 and CD206 were detected by flow cytometry.ELISA was use to detect cytokines IL-10 and IL-12p70,immunofluorescence was use to detect iNOS and Arg-1.Western blot was used to detect polariza-tion related pathway proteins,and whether medium and low doses of radiation could alter polarization type of TAMs was observed.Results:4T1-TCS induced TAM had decreasing NO secretion and increasing CD206 and Arg-1 expressions,iNOS expression was decreased;with low doses irradiation(0.075 Gy,0.5 Gy,1 Gy)of TCS-TAM,compared with non irradiation group,NO secretion,expressions of CD86,CD206,Arg-1 and iNOS showed no significant changes;medium doses(2 Gy,4 Gy,6 Gy)of irradiation on TCS-TAM resulted in increased secretion of NO,and flow cytometry results showed increased expressions of CD86,decreased CD206 expression;immunofluorescence results showed an increase in iNOS expression and a decrease in Arg-1 expression in cells;ELISA results showed an increase in secretion of IL-12p70 by cells and a decrease in secretion of IL-10.Western blot results showed that NOX2,ATMS1981*,IRF5 proteins expressions were increased.Conclusion:4T1-TCS can successfully induce macrophage RAW264.7 polarize into M2 phenotype,while low dose irradiation has no significant effect on polarization phenotype of TCS-TAM.Medium dose irradiation can induce TCS-TAM polarization into M1 phenotype that inhibits tumor growth,and reversal mechanism of polarization may be related to IRF5 pathway.


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