1.Study on the effect of apoptosis stimulation protein 2 on traumatic proliferative vitreoretinopathy in rabbits
Xiaoli CHEN ; Yuze MAO ; Wenhui CAI ; Haiwei WANG ; Yankun YUE
International Eye Science 2026;26(1):16-20
AIM:To investigate the effect of apoptosis stimulation protein 2(ASPP2)on the development of traumatic proliferative vitreoretinopathy(PVR)in a rabbit model.METHODS:A total of 30 New Zealand white rabbits were selected, and the right eyes of all rabbits were inflicted with a scleral penetrating wound of approximately 6 mm. Then rabbits were randomly and evenly divided into experimental and control group. The experimental group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with lentivirus-ASPP2, while the control group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with negative control lentivirus. At 1, 2, 3, and 4 wk after PVR modeling, a handheld tonometer was used to measure the intraocular pressure. Moreover, fundus photography and ocular ultrasound examination were performed to detect the retinal proliferation. At 4 wk after modeling, hematoxylin-eosin staining was used to observe the morphological retinal changes, and Western blot was used to determine the protein expressions of ASPP2 and the epithelial-mesenchymal transition(EMT)marker Vimentin in the rabbit retinas.RESULTS:At 1, 2, 3, and 4 wk after modeling, there were no significant changes in intraocular pressure within the experimental and control group of rabbit eyes, either before or after PVR modeling, the success rate of PVR modeling in the experimental group was lower than that in the control group(P<0.05), and the retinal proliferation and structural disorder was less severe in the experimental group. At 4 wk after modeling, the retinal protein expression level of ASPP2 in the experimental group was significantly higher than that in the control group(t=3.193, P=0.033), while the Vimentin protein expression level was significantly lower in the experimental group(t=-3.599, P=0.023).CONCLUSION:ASPP2 may be involved in regulating the process of EMT in retinal pigment epithelial cells, thereby delaying the development and progression of traumatic PVR in rabbit eyes.
2.Correlation Analysis of Serum miR-489-3p and miR-214-3p Level Expression with Disease Severity in Psoriasis Patients
Xing GUO ; Qing LI ; Peining MA ; Dengxin JIA ; Zengshan JIN ; Jing XU ; Xuesong HAN ; Zhifeng YUE ; Yubao CHEN
Journal of Modern Laboratory Medicine 2025;40(5):52-56,72
Objective To investigate the correlation between serum levels of microRNA(miR)-489-3p and miR-214-3p in patients with Psoriasis and the severity of disease.Methods From March 2022 to January 2024,138 Psoriasis patients who visited Zhangjiakou First Hospital were regarded as the study subjects(disease group).According to the psoriasis area and severity index(PASI)score,the 138 Psoriasis patients were separated into mild group(n=46),moderate group(n=54)and severe group(n=38).112 healthy individuals who underwent physical examinations in Zhangjiakou First Hospital during the same period were included in the control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to determine the serum levels of miR-489-3p and miR-214-3p in the subjects.The serum levels of miR-489-3p and miR-214-3p were compared between the disease group and the control group,and among patients with different degrees of disease.Spearman correlation analysis was applied to explore the relationship between serum miR-489-3p,miR-214-3p levels and disease severity in Psoriasis patients.Logistic regression analysis was performed to analyze the related factors affecting the severity of Psoriasis.Receiver operating characteristic(ROC)curve was applied to investigate the diagnostic value of serum miR-489-3p and miR-214-3p levels for severe Psoriasis.Results The serum levels of miR-489-3p(0.81±0.23)and miR-214-3p(0.79±0.22)in the disease group were lower than those in the control group(1.05±0.28,1.02±0.25),and the differences were statistically significant(t=7.441,7.732,all P<0.05).Serum miR-489-3p in mild,moderate and severe Psoriasis groups(0.93±0.24,0.80±0.23,0.69±0.22),miR-214-3p levels(0.91±0.24,0.77±0.22,0.66±0.21)decreased gradually,and the differences were statistically significant(F=12.423,13.168,all P<0.05).Spearman's results showed that serum levels of miR-489-3p and miR-214-3p were negatively correlated with the severity of Psoriasis in patients(r=-0.490,-0.463,all P<0.05).Serum miR-489-3p and miR-214-3p were independent protective factors for the severity of Psoriasis patients(Wald χ2=5.751,8.753,all P<0.05).ROC curve results showed that the area under the curve(AUC)of serum miR-489-3p and miR-214-3p for diagnosing severe Psoriasis alone was 0.785 and 0.792,with sensitivity of 78.9%and 73.7%,specificity of 49.9%and 54.7%,respectively.The AUC of the combined diagnosis for severe Psoriasis was 0.931,the sensitivity and specificity were 71.7%,71.1%,respectively,and the combined diagnostic efficacy of the two was better than that of miR-489-3p and miR-214-3p alone,and the differences were statistically significant(Z=3.018,2.773,all P<0.05).Conclusion The serum levels of miR-489-3p and miR-214-3p in patients with Psoriasis are both reduced,and both are negatively correlated with the severity of the disease in Psoriasis patients.The combined determination of the two has high efficacy in the diagnosis of severe Psoriasis.
3.Construction and validation of a risk prediction model for hypoglycemia in adult intensive care unit patients
Mengdie CHEN ; Yan YUE ; Shuhan TU ; Qian LI ; Qian XING ; Gang YI
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(4):460-466
Objective To screen the risk factors for hypoglycemia in adult intensive care unit(ICU)patients,construct a risk prediction model,and validate its predictive effect.Methods A retrospective study was conducted on adult critically ill patients admitted to the general ICU of Hospital of Chengdu University of Traditional Chinese Medicine from December 2023 to September 2024.Patients admitted from December 2023 to June 2024 served as the modeling group,and those from July to September 2024 as the validation group.A total of 928 patients were included,with 650 in the modeling group and 278 in the validation group.After literature review and expert consultation,27 potential risk factors for hypoglycemia in ICU patients were initially screened,and data were collected including general information[gender,age,acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,nutrition risk in critically ill(NUTRIC)score,mechanical ventilation status,hemodialysis status,enteral nutrition status],disease data(sepsis,liver disease history,kidney disease history,diabetes history,hypoglycemia history),blood glucose-related indicators[mean blood glucose,blood glucose coefficient of variation,insulin dosage,intravenous insulin titration use,inotropic drug use,insulin secretagogues(Sulfonylureas and Glinides),and combined use of hypoglycemic drugs(two or more)],and laboratory indicators[serum creatinine(SCr),blood urea nitrogen(BUN),serum albumin(Alb),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),glomerular filtration rate(GFR)].The patients were divided into a hypoglycemia group and a non-hypoglycemia group based on the occurrence of hypoglycemia.Univariate analysis and binary Logistic regression analysis were used to identify influencing factors of hypoglycemia in adult ICU patients,and a nomogram prediction model was constructed.The area under the receiver operator characteristic curve(AUC)and calibration curves were employed to evaluate the discrimination and calibration of the model.Results The modeling cohort included 552 non-hypoglycemic patients and 98 hypoglycemic patients,with an ICU hypoglycemia incidence rate of 15.1%.Compared with the hypoglycemia group,the non-hypoglycemia group showed significantly lower proportions of patients with renal disease history,diabetes history,hypoglycemia history,undergoing hemodialysis,using intravenous insulin titration,and combined use of hypoglycemic drugs,as well as lower blood glucose coefficient of variation,lower APACHEⅡ scores,and significantly elevated GFR(all P<0.05).Binary Logistic regression analysis was performed using the 9 variables with statistically significant differences in univariate analysis as independent variables and hypoglycemia occurrence as the dependent variable.The results indicated that a history of diabetes,a history of hypoglycemia,APACHEⅡ score,GFR,blood glucose coefficient of variation,and combined use of hypoglycemic drugs were independent risk factors for hypoglycemia in ICU patients[odds ratios(OR)were 1.761,2.095,1.048,0.990,1.029,and 1.975,respectively,and 95%confidence intervals(95%CI)were 1.052-2.949,1.220-3.600,1.022-1.074,0.982-0.997,1.013-1.046,and 1.145-3.408,respectively.The corresponding Pvalues were 0.031,0.007,0.000,0.009,<0.001,0.014].A nomogram prediction model for hypoglycemia in ICU patients was constructed using six independent predictors selected through binary logistic regression analysis.The ROC curve AUC for the modeling group was 0.884(95%CI 0.826-0.941,P=0.250),with a maximum Youden index of 0.713,sensitivity of 92.1%,and specificity of 79.2%.The validation cohort included 38 patients with hypoglycemia and 240 patients without hypoglycemia.Compared with the hypoglycemia group,the non-hypoglycemia group showed significantly lower proportions of patients with a history of diabetes,a history of hypoglycemia,and combined use of hypoglycemic drugs,as well as lower APACHEⅡ scores and lower blood glucose coefficient of variation,with significantly increased GFR(all P<0.05).The ROC curve AUC for the validation cohort was 0.803(95%CI was 0.757-0.849,P=0.138),indicating high discriminatory ability.The predicted probability at the diagnostic cutoff point was P=0.138.The model's diagnostic threshold for predicted probability was P=0.138,while the optimal cut-off value based on the Youden index was 0.513,yielding a sensitivity of 76.5%and specificity of 74.8%,indicating predictive value for hypoglycemia in adult ICU patients.The mean absolute error(MAE)results for the modeling group and validation group were<0.05.The calibration curves of both the modeling and validation groups showed close alignment with the ideal curve,indicating excellent calibration performance of the model.Conclusion The constructed hypoglycemia risk prediction model for adult ICU patients has good predictive performance,which can quickly identify high-risk populations of hypoglycemia in ICU and provide reference for clinical preventive nursing.
4.Expert consensus on pre-hospital emergency management of heatstroke(2024 edition)
Tao WANG ; Yue ZHAO ; Meng WANG ; Hai-Yan ZHU ; Chen LI ; Yu-Jian CHEN ; Qin-Rui XING ; Qing SONG
Medical Journal of Chinese People's Liberation Army 2025;50(3):245-253
Heatstroke,especially in high-temperature and high-humidity environments,is a life-threatening acute heat-injury disease that seriously endangers human health.Timely and effective on-site treatment is crucial for patients'survival and prognosis.Early recognition,rapid assessment,and on-site cooling are the core of pre-hospital treatment of heatstroke.Currently,there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke.Therefore,the"Expert Consensus on Pre-hospital Emergency Management of Heatstroke(2024 edition)"was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care,emergency departments,and intensive care units.This consensus focuses on heatstroke prevention,on-site and ambulance-based treatment,and early emergency room interventions,and puts forward 10 evidence-based recommendations,aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.
5.Correlation Analysis of Serum miR-489-3p and miR-214-3p Level Expression with Disease Severity in Psoriasis Patients
Xing GUO ; Qing LI ; Peining MA ; Dengxin JIA ; Zengshan JIN ; Jing XU ; Xuesong HAN ; Zhifeng YUE ; Yubao CHEN
Journal of Modern Laboratory Medicine 2025;40(5):52-56,72
Objective To investigate the correlation between serum levels of microRNA(miR)-489-3p and miR-214-3p in patients with Psoriasis and the severity of disease.Methods From March 2022 to January 2024,138 Psoriasis patients who visited Zhangjiakou First Hospital were regarded as the study subjects(disease group).According to the psoriasis area and severity index(PASI)score,the 138 Psoriasis patients were separated into mild group(n=46),moderate group(n=54)and severe group(n=38).112 healthy individuals who underwent physical examinations in Zhangjiakou First Hospital during the same period were included in the control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to determine the serum levels of miR-489-3p and miR-214-3p in the subjects.The serum levels of miR-489-3p and miR-214-3p were compared between the disease group and the control group,and among patients with different degrees of disease.Spearman correlation analysis was applied to explore the relationship between serum miR-489-3p,miR-214-3p levels and disease severity in Psoriasis patients.Logistic regression analysis was performed to analyze the related factors affecting the severity of Psoriasis.Receiver operating characteristic(ROC)curve was applied to investigate the diagnostic value of serum miR-489-3p and miR-214-3p levels for severe Psoriasis.Results The serum levels of miR-489-3p(0.81±0.23)and miR-214-3p(0.79±0.22)in the disease group were lower than those in the control group(1.05±0.28,1.02±0.25),and the differences were statistically significant(t=7.441,7.732,all P<0.05).Serum miR-489-3p in mild,moderate and severe Psoriasis groups(0.93±0.24,0.80±0.23,0.69±0.22),miR-214-3p levels(0.91±0.24,0.77±0.22,0.66±0.21)decreased gradually,and the differences were statistically significant(F=12.423,13.168,all P<0.05).Spearman's results showed that serum levels of miR-489-3p and miR-214-3p were negatively correlated with the severity of Psoriasis in patients(r=-0.490,-0.463,all P<0.05).Serum miR-489-3p and miR-214-3p were independent protective factors for the severity of Psoriasis patients(Wald χ2=5.751,8.753,all P<0.05).ROC curve results showed that the area under the curve(AUC)of serum miR-489-3p and miR-214-3p for diagnosing severe Psoriasis alone was 0.785 and 0.792,with sensitivity of 78.9%and 73.7%,specificity of 49.9%and 54.7%,respectively.The AUC of the combined diagnosis for severe Psoriasis was 0.931,the sensitivity and specificity were 71.7%,71.1%,respectively,and the combined diagnostic efficacy of the two was better than that of miR-489-3p and miR-214-3p alone,and the differences were statistically significant(Z=3.018,2.773,all P<0.05).Conclusion The serum levels of miR-489-3p and miR-214-3p in patients with Psoriasis are both reduced,and both are negatively correlated with the severity of the disease in Psoriasis patients.The combined determination of the two has high efficacy in the diagnosis of severe Psoriasis.
6.Preliminary establishment of reference intervals for 12 cytokines in adult plasma by multiplex bead-based flow fluorescent immunoassay
Xinyu WANG ; Xing CHENG ; Lu ZHENG ; Yue ZHANG ; Yuting MA ; Guoping NIU ; Feng GU ; Yongqiang CHEN
Chinese Journal of Immunology 2025;41(5):1202-1207
Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95%reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.
7.Preliminary establishment of reference intervals for 12 cytokines in adult plasma by multiplex bead-based flow fluorescent immunoassay
Xinyu WANG ; Xing CHENG ; Lu ZHENG ; Yue ZHANG ; Yuting MA ; Guoping NIU ; Feng GU ; Yongqiang CHEN
Chinese Journal of Immunology 2025;41(5):1202-1207
Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95%reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.
8.Processing technology of calcined Magnetitum based on concept of QbD and its XRD characteristic spectra.
De-Wen ZENG ; Jing-Wei ZHOU ; Tian-Xing HE ; Yu-Mei CHEN ; Huan-Huan XU ; Jian FENG ; Yue YANG ; Xin CHEN ; Jia-Liang ZOU ; Lin CHEN ; Hong-Ping CHEN ; Shi-Lin CHEN ; Yuan HU ; You-Ping LIU
China Journal of Chinese Materia Medica 2025;50(9):2391-2403
Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods*
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Drugs, Chinese Herbal/chemistry*
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Quality Control
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Particle Size
9.Tanreqing Capsules protect lung and gut of mice infected with influenza virus via "lung-gut axis".
Nai-Fan DUAN ; Yuan-Yuan YU ; Yu-Rong HE ; Feng CHEN ; Lin-Qiong ZHOU ; Ya-Lan LI ; Shi-Qi SUN ; Yan XUE ; Xing ZHANG ; Gui-Hua XU ; Yue-Juan ZHENG ; Wei ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2270-2281
This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified_f_Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Lung/metabolism*
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Mice, Inbred C57BL
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Capsules
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Orthomyxoviridae Infections/virology*
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Gastrointestinal Microbiome/drug effects*
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Male
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Humans
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Female
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Influenza A virus/physiology*
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Influenza, Human/virology*
10.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C

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