1.Mechanism of Number 2 Feibi Recipe in Ameliorating Pulmonary Fibrosis in Mice by Modulating Endoplasmic Reticulum Stress in AT2 Cells to Attenuate Apoptosis and Promote Alveolar Repair
Yaodong CAI ; Jialing BEI ; Wan WEI ; Chengyan XU ; Yanli LIU ; Yong WANG ; Yang JIAO ; Yun CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):80-92
ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe (N2FBR) in idiopathic pulmonary fibrosis (IPF), focusing on its effects on endoplasmic reticulum (ER) stress, apoptosis, stemness maintenance, and regenerative capacity of alveolar type Ⅱ epithelial cells (AT2 cells), and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin (BLM). Mice were randomly divided into blank control, model, low-, and high-dose N2FBR intervention groups (9.1, 18.2 g·kg-1), and prednisolone intervention group (6.5 mg·kg-1). Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin (HE) and Masson's trichrome staining. Hydroxyproline (HYP) content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors, including collagen type Ⅰ alpha 1 chain (ColIa1), alpha-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase 1 (Timp1), were detected by real-time polymerase chain reaction (Real-time PCR). Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C (SPC) and cysteine-aspartic protease-3 (Caspase-3). Endoplasmic reticulum (ER) stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase (PERK). Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy (TEM). The expression levels of key proteins involved in ER stress and apoptosis pathways, including PERK, activating transcription factor 4 (ATF4), and Caspase-3, were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen (Ki-67) was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology (labeling AT2 cells with GFP) combined with Krt8 labeling was used to evaluate intermediate differentiation states, and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells (AT1) was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue, increased collagen deposition, elevated lung coefficient, decreased pulmonary function, and upregulation of fibrosis-related factors (P<0.01). High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction, significantly reduced HYP content (P<0.01), and significantly downregulated ColIa1, α-SMA, and Timp1 expression (P<0.01). Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group, which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group, which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group, which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4, as well as the apoptosis-related protein Caspase-3, were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group, which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells, the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group (P<0.01). Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive (Krt8⁺GFP⁺) cells increased in the model group, indicating differentiation arrest. This proportion was significantly reduced in the treatment group, and the morphology of GFP⁺ cells exhibited a flattened, extended shape, suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells, reduces AT2 cell apoptosis, restores lamellar body structure and function, enhances proliferation activity, and alleviates differentiation arrest to promote differentiation into AT1 cells, thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi, harmonizing Qi and blood, and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells, providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.
2.Mechanism of Number 2 Feibi Recipe in Ameliorating Pulmonary Fibrosis in Mice by Modulating Endoplasmic Reticulum Stress in AT2 Cells to Attenuate Apoptosis and Promote Alveolar Repair
Yaodong CAI ; Jialing BEI ; Wan WEI ; Chengyan XU ; Yanli LIU ; Yong WANG ; Yang JIAO ; Yun CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):80-92
ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe (N2FBR) in idiopathic pulmonary fibrosis (IPF), focusing on its effects on endoplasmic reticulum (ER) stress, apoptosis, stemness maintenance, and regenerative capacity of alveolar type Ⅱ epithelial cells (AT2 cells), and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin (BLM). Mice were randomly divided into blank control, model, low-, and high-dose N2FBR intervention groups (9.1, 18.2 g·kg-1), and prednisolone intervention group (6.5 mg·kg-1). Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin (HE) and Masson's trichrome staining. Hydroxyproline (HYP) content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors, including collagen type Ⅰ alpha 1 chain (ColIa1), alpha-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase 1 (Timp1), were detected by real-time polymerase chain reaction (Real-time PCR). Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C (SPC) and cysteine-aspartic protease-3 (Caspase-3). Endoplasmic reticulum (ER) stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase (PERK). Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy (TEM). The expression levels of key proteins involved in ER stress and apoptosis pathways, including PERK, activating transcription factor 4 (ATF4), and Caspase-3, were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen (Ki-67) was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology (labeling AT2 cells with GFP) combined with Krt8 labeling was used to evaluate intermediate differentiation states, and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells (AT1) was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue, increased collagen deposition, elevated lung coefficient, decreased pulmonary function, and upregulation of fibrosis-related factors (P<0.01). High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction, significantly reduced HYP content (P<0.01), and significantly downregulated ColIa1, α-SMA, and Timp1 expression (P<0.01). Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group, which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group, which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group, which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4, as well as the apoptosis-related protein Caspase-3, were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group, which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells, the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group (P<0.01). Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive (Krt8⁺GFP⁺) cells increased in the model group, indicating differentiation arrest. This proportion was significantly reduced in the treatment group, and the morphology of GFP⁺ cells exhibited a flattened, extended shape, suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells, reduces AT2 cell apoptosis, restores lamellar body structure and function, enhances proliferation activity, and alleviates differentiation arrest to promote differentiation into AT1 cells, thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi, harmonizing Qi and blood, and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells, providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.
3.Mechanism of Colquhounia Root Tablets against diabetic kidney disease via RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis.
Ming-Zhu XU ; Zhao-Chen MA ; Zi-Qing XIAO ; Shuang-Rong GAO ; Yi-Xin YANG ; Jia-Yun SHEN ; Chu ZHANG ; Feng HUANG ; Jiang-Rui WANG ; Bei-Lei CAI ; Na LIN ; Yan-Qiong ZHANG
China Journal of Chinese Materia Medica 2025;50(7):1830-1840
This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals
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Diabetic Nephropathies/metabolism*
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Receptor for Advanced Glycation End Products/genetics*
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NF-kappa B/genetics*
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Signal Transduction/drug effects*
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Rats
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Proto-Oncogene Proteins c-akt/genetics*
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Drugs, Chinese Herbal/administration & dosage*
;
Male
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Phosphatidylinositol 3-Kinases/genetics*
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Reactive Oxygen Species/metabolism*
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Humans
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Plant Roots/chemistry*
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Rats, Sprague-Dawley
;
Tablets/administration & dosage*
4.Advances in clinical pharmacotherapy for neonatal Ureaplasma urealyticum infection.
Bei-Bo CAI ; Fei-Fei CHEN ; Fang LUO
Chinese Journal of Contemporary Pediatrics 2025;27(10):1286-1290
Ureaplasma urealyticum (UU) is a common pathogen colonizing or infecting the neonatal respiratory tract. It can be vertically transmitted from mother to infant, irrespective of the duration of premature rupture of membranes and the mode of delivery. UU infection is an important factor contributing to preterm birth and low birth weight and is closely associated with adverse outcomes such as bronchopulmonary dysplasia and neurodevelopmental impairment. Given the immaturity of neonatal immune and organ systems, pharmacologic treatment must balance efficacy and safety. Currently, no unified standard regimen has been established for the treatment of neonatal UU infection. This review summarizes pharmacotherapeutic options for neonatal UU infection to inform clinical practice.
Humans
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Ureaplasma Infections/drug therapy*
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Infant, Newborn
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Ureaplasma urealyticum
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Anti-Bacterial Agents/therapeutic use*
5.Traditional Chinese Medicine approaches to syndrome differentiation and treatment of sleep disorders based on the theory of"One Guiding Principle and Four Specific Methods"
Bei CHEN ; Yulun WU ; Weijie ZHU ; Junjie CAI ; Menghan ZHANG ; Xuejuan LIN ; Yimeng CHEN
Space Medicine & Medical Engineering 2025;36(4):337-342
This paper focuses on extreme environments and systematically analyzes sleep disorders caused by multiple pathogenesis,including circadian rhythm disorder,yin-yang imbalance and qi-blood disorder under weightlessness,emotional depression due to environmental changes,abnormal diet and excretion,and six excesses pathogenic factors,in accordance with the theory of correspondence between nature and human.It proposes harmonizing yin and yang as the core therapeutic principle and guiding framework,with specific methods including calming rebellious qi-blood,regulating qi movement,harmonizing heart and kidney,and dredging and regulating blood vessels,thus forming the"one guiding principle and four specific methods"treatment strategy.Additionally,by integrating the modified application of classic formulas,a diagnostic and therapeutic approach targeting multi-dimensional pathogenesis is established.This study aims to promote the in-depth integration of Traditional Chinese Medicine(TCM)in extreme environmental medicine through TCM theories and innovative application of prescriptions,provide TCM-characterized solutions for health management of workers in extreme environments,and facilitate the transformation of extreme environmental medicine toward the modern medical model of"prevention-treatment integration".
6.Anatomical structures of the matrix channel network for interstitial fluid flow in the human hand
Tian-Tian LI ; Jian-Ping ZHAO ; Chao-Zhi YANG ; Zhen CHEN ; Nai-Li WANG ; Bei LI ; Jin CAI ; Xiao-Yu WANG ; Hong-Yi LI
Acta Anatomica Sinica 2025;56(3):307-314
Objective To investigate the anatomical and microscopic structures of interstitial fluid flow channels in the skin tissue of hand dorsum in human cadavers.Methods Totally 7 fresh cadavers within 12 hours post-mortem were included.MRI was used to observe the distribution of interstitial fluid flow from the first phalanx of the fingers to the wrist,precisely locating the flow channels.Based on imaging results,histological analyses were conducted to determine the histological characteristics of the flow channels.Furthermore,multi-immunofluorescence and microcomputed tomography(Micro-CT)techniques were employed to analyze the channels,and image post-processing was used to elucidate their anatomical structures at the microscopic level.Results After injecting a contrast agent into the first phalanx of ten finger specimens and applying repeated pressure,MRI image revealed centripetal long-range interstitial fluid flow along channels distinct from blood vessels and lymphatic vessels.Histological analysis and Micro-CT further confirmed that the flow primarily occurred within the fibrous connective tissue and adventitia of the skin.Conclusion The orderly fibrous connective tissue and adventitia in the skin form the interstitial fluid flow channels in the human hand dorsum skin,named as"stromal membrane channels"in the skin.
7.The characteristics and implication of WHO Essential Medicines Model List 2023
Yu-Bei HAN ; Wen-Chen LIU ; Chen CHEN ; Cai-Jun YANG ; Yu FANG
Chinese Journal of Health Policy 2024;17(2):53-58
The present analysis was based on the iteration of the 2023 WHO Essential Medicines Model List(23rd list)and Essential Medicines Model List for Children(9th list).In a methodological fashion,the adjustment procedure of the basic drug list and the materials required to submit the application were sorted out.Subsequently,a comprehensive synthesis of predominant features characterizing the 2023 edition of the EML and EMLc are summarized(offered).Notably,this edition boasts the highest count of medicines ever included featuring extensive inclusion of innovative drugs to fill the gap,select medicines for children carefully,and the emphasizing on clinical benefit evidence and public health affordability.It is suggested that China should update the NEML according to the national conditions and the experience of WHO as soon as possible,pay attention to the difference and connection between the list of essential medicines and the list of medical insurance,and play a meticulous role for establishing effective linkages between two lists.Such measures are envisaged to meet the basic drug needs,and ensure the accessibility and affordability of drugs,thereby optimizing the allocation of health resources.
8.Analysis of the effectiveness of cross-reactive carbohydrate antigen determinant antibody adsorbents in identifying allergen-specific IgE antibodies
Wenling ZHAO ; Bei CAI ; Chuqi SHI ; Zhenzhen SU ; Weihua FENG
Chinese Journal of Preventive Medicine 2024;58(9):1379-1383
This study aimed to investigate the influence of anti-cross-reactive carbohydrate determinant IgE antibodies (anti-CCD IgE) on the detection of allergen-specific IgE (sIgE) antibodies, as well as the application value of anti-CCD IgE adsorbents in detecting allergen sIgE. In this cross-sectional study, a total of 2 636 test samples from patients who received treatment in West China Hospital of Sichuan University and tested allergen sIgE using the western blot method from October 2020 to May 2021 were analyzed. In these samples, 709 samples tested postive of allergen sIgE. 46 stochastic venous serum samples that tested positive in both sIgE and anti-CCD IgE and 1 serum sample that tested positive in sIgE but negative in anti-CCD IgE were collected. These samples were processed by anti-CCD IgE adsorbents, followed by allergen sIgE detection. The difference between the two detection results before and after adsorption was analyzed. The allergen test results showed that the positive rate of anti-CCD IgE in samples was 2.6% (69/2 636) during the period of sample collection. After treatment with anti-CCD IgE adsorbents, the top three allergen-sIgE of the positive rate changed from tree combination 2 (willow/poplar/elm), common ragweed and peanut to dust mite combination, cockroach and crab. The positive anti-CCD IgE results of 46 samples all turned negative and the total positive sIgE antibody dropped by 62.8%; the positive rate of sIgE antibodies with the class result ≥2 significantly decreased after treatment with anti-CCD IgE adsorbents, especially the positive rate of common ragweed dropped by 96.2%. The results of positive samples showed that multiple sIgE antibodies declined by different ranges, involving up to 11 antibodies with a maximum decline of 4 classes. Strongly positive sIgE antibodies (the class result ≥4) also had a high conversion rate of negative (25.0%-100%). The positive sIgE antibodies in about 60% of the samples decreased by more than 2, and the sIgE antibodies in 17.4% of the samples turned completely negative. There was no change in the allergen sIgE detection results of the sample with negative anti-CCD IgE after treatment. In conclusion, sIgE antibodies including targeting common ragweed, humulus, tree combination 2 (willow/poplar/elm), etc. are susceptible to false positives caused by anti-CCD IgE. Treatment of samples with anti-CCD IgE adsorbents can significantly reduce the risk of false positives caused by anti-CCD IgE. It is necessary to pretreat samples that were anti-CCD IgE positive with anti-CCD IgE adsorbents, which can make laboratory results more accurate and provide a reference for diagnosis and prevention of allergic diseases.
9.Factors affecting sleep disorders among pregnant women
CAI Fengcheng ; XU Mengyan ; WU Yingying ; LIU Bei ; ZHU Li
Journal of Preventive Medicine 2024;36(5):440-443
Objective:
To investigate the current status and influencing factors of sleep disorders among pregnant women, so as to provide insights into health management during pregnancy.
Methods:
Pregnant women who underwent prenatal checkups at Hangzhou Obstetrics and Gynecology Hospital from January to October 2023 were selected as subjects, and general data including age, pregnancy period and exercise were collected through questionnaire surveys. Sleep quality, pregnancy stress, anxiety and depression were evaluated using Pittsburgh Sleep Quality Index, Pregnancy Stress Rating Scale, Pregnancy-related Anxiety Scale and Edinburgh Postnatal Depression Scale, respectively. Factors affecting sleep disorders among pregnant women were analyzed using a multivariable logistic regression model.
Results:
A total of 386 pregnant women was surveyed, with a mean age of (30.28±4.65) years, including 20.47% in the first trimester, 47.93% in the second trimester and 31.61% in the third trimester. Women with anxiety and depression accounted for 14.51% and 21.76%, respectively. Pregnancy stress was mainly moderate, accounting for 51.04%. There were 106 pregnant women with sleep disorders, accounting for 27.46%. Mutivariable logistic regression analysis showed that age (≥35 years, OR=1.656, 95%CI: 1.094-2.503), pregnancy period (third pregnancy, OR=2.097, 95%CI: 1.213-3.621), regular exercise in the past 6 months (OR=0.376, 95%CI: 0.210-0.670), anxiety (OR=2.794, 95%CI: 1.545-5.048), depression (OR=3.501, 95%CI: 1.877-6.529) and pregnancy stress (moderate, OR=1.355, 95%CI: 1.018-1.801; severe, OR=2.538, 95%CI: 1.417-4.540) were the factors affecting sleep disorders among pregnant women.
Conclusions
Sleep disorders of pregnant women is influenced by age, pregnancy period, pregnancy stress, anxiety, depression and exercise. It is necessary to identify high-risk individuals with sleep disorders early, and to provide psychological intervention and prenatal health guidance.
10.Clinical effects of Xiao'er Chiqiao Qingre Granules combined with conventional treatment on patients with pediatric acute viral infection of lower respiratory tract
Ying-Nan SUN ; Li YANG ; Bei-Bei CAI ; Wei PAN
Chinese Traditional Patent Medicine 2024;46(11):3640-3644
AIM To investigate the clinical effects of Xiao'er Chiqiao Qingre Granules combined with conventional treatment on patients with pediatric acute viral infection of lower respiratory tract.METHODS Ninety-nine patients were randomly assigned into control group(49 cases)for intervention of conventional treatment,and observation group(50 cases)for intervention of both Xiao'er Chiqiao Qingre Granules and conventional treatment.The changes in clinical effects,TCM syndrome scores,symptom disappearing time[fever reduction time,nasal congestion(lung rales,wheezing,cough)disappearance time],CRP,TNF-α,CD4+,CD8+,CD4+/CD8+and lung function indices(FEV1,FVC,PEF,MVV)were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05),along with shorter symptom disappearing time(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,CRP,TNF-α,CD8+(P<0.05),and increased CD4+,CD4+/CD8+,lung function indices(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with pediatric acute viral infection of lower respiratory tract,Xiao'er Chiqiao Qingre Granules combined with conventional treatment can regulate body immunity,decrease CRP,TNF-α levels,reduce inflammatory injury


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