1.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
2.Clinical analysis of re-fracture after bone healing treated with combined surgery for congenital pseudarthrosis of the tibia in children
Xiping LIU ; Kun LIU ; Guanghui ZHU
Chinese Journal of Orthopaedics 2024;44(5):315-321
Objective:To explore the possible risks of re-fracture after bone healing in children with congenital pseudarthrosis of the tibia, who were treated with combined surgery.Methods:56 children (35 males and 21 females, with an average age of 38.0±9.2 months ranging from 18 to 66 months) with re-fracture after bone healing were retrospectively enrolled from January 2007 to August 2016, during which a total of 142 children with CPT underwent combined surgical treatment in the orthopedics department of Hunan Children's Hospital. Complete healing of the tibial pseudarthrosis, trauma after surgery, breakage of fibula, and the distal end of the tibial intramedullary rod located in the tibial medullary cavity or not were hypothesized as 4 risk factors. Univariate logistic regression analysis was conducted to investigate the correlation between these factors and re-fractures after tibial pseudarthrosis healing.Results:The average follow-up was 81.7±10.8 months ranging from 60 to 120 months with at least 5 years after bone healing. For complete or partial healing of the tibial pseudarthrosis after surgery, the number of re-fractures was 48 and 8, respectively; For with or without a history of trauma, the number of re-fractures was 50 and 6, respectively; for with an intact or broken fibula after surgery, the number of re-fractures was 7 and 49, respectively; For entry or no entry of the intramedullary rod into the tibial medullary cavity, the number of re-fractures was 44 and 12, respectively. The results of univariate logistic regression analysis showed that partial healing of the tibial pseudarthrosis after surgery [ OR=0.255, 95% CI (0.107, 0.605), P=0.002], history of trauma [ OR=36.458, 95% CI (13.332, 99.701), P<0.001], incomplete fibula [ OR=0.267, 95% CI (0.108, 0.661), P=0.004], and intramedullary rod insertion into the tibial medullary cavity [ OR=2.640, 95% CI (1.224, 5.695), P=0.013] were associated with re-fracture after bone healing. The number and proportion of cases with recurrent fractures occurring ≤1, 1-3, 3-6, ≥6 years after bone healing were 5 cases, 9% (5/56), 14 cases, 25% (14/56), 22 cases, 39% (22/56), 15 cases, and 27% (15/56), respectively, the difference was statistically significant (χ 2=11.569, P=0.009). With the extension of follow-up time, the number of cases of re-fractures after bone healing increases, mostly occurring more than one year after bone healing. There were 44 cases (47%, 44/94) and 12 cases (25%, 12/48) of re fractures after bone healing in 94 cases of distal intramedullary rods in the tibial medullary cavity and 48 cases of cross ankle joint fixation, respectively. The difference in the incidence of re-fractures was statistically significant (χ 2=6.327, P=0.018). The incidence of intramedullary rod displacement in cases where the distal end of the intramedullary rod is located within the tibial medullary cavity was 100%. Conclusions:Factors of partial healing of the tibial pseudarthrosis, a history of trauma, incomplete status of the fibula after surgery, and intramedullary rod's entry into the tibia were risk factors for re-fracture after bone healing treated with combined surgery for CPT. After the healing of the tibial pseudarthrosis, it is not advisable to push the tibial intramedullary rod into the tibial medullary cavity, which can cause unstable fixation of the tibial intramedullary rod and result in displacement, and even affect the development of the tibial mechanical axis or the occurrence of re-fractures.
3.Application of Suture Traction Suspension Method in Anterior Chest Approach Endoscopic Thyroid Cancer Radical Surgery
Zhenhua ZHOU ; Xiping LIU ; Ke SUN
Chinese Journal of Minimally Invasive Surgery 2024;24(1):19-24
Objective To explore the application value of suture traction suspension method in endoscopic thyroid cancer radical surgery through the anterior chest approach.Methods A retrospective analysis was made on 108 cases of papillary thyroid cancer from January 2020 to December 2022,who underwent unilateral lobectomy and ipsilateral central lymph node dissection through anterior chest approach.After May 2021,the suture traction and suspension method was gradually carried out by using 2-0 polypropylene suture to suspend the muscles,trachea,and thyroid gland lobes.There were 51 cases in the suture traction suspension group and 57 cases in the conventional endoscopic group.The intraoperative and postoperative indicators were compared between the two groups.Results The surgery was successfully completed in both groups.As compared to the conventional endoscopic group,the suture traction suspension group had shorter surgical time for thyroidectomy[(35.3±7.3)min vs.(43.4±8.4)min,t =-5.342,P<0.001],shorter surgical time for central lymph node dissection[(20.1±3.5)min vs.(27.7±4.9)min,t =-9.271,P<0.001],less intraoperative bleeding[10(5-15)ml vs.15(5-30)ml,Z =-6.250,P<0.001],and more central lymph nodes dissected[8(3-13)vs.6(4-10),Z =3.272,P =0.001].There were fewer cases of transient recurrent laryngeal nerve injury after surgery in the suture traction suspension group,but no statistical significance was noted(1 case vs.8 cases,χ2 =3.678,P =0.055).There were no statistically significant differences in postoperative hospitalization time,postoperative lymph leakage,parathyroid gland detection in postoperative specimens,postoperative hypoparathyroidism,postoperative pain score,and postoperative cosmetic effect score between the two groups(P>0.05).Conclusion Suture traction suspension method can shorten surgical time,reduce intraoperative bleeding,reduce the occurrence of recurrent laryngeal nerve injury,and increase the number of central lymph node dissection.
4.Effects of Lumbricus Protein on Phenotypic Transformation of Corporal Cavernous Smooth Muscle Cells and Erectile Dysfunction in Rats with Diabetic Erectile Dysfunction
Xiaowei JI ; Aiping ZHANG ; Liming LIU ; Jiashu YANG ; Xiping XING
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):325-333
Objective To investigate the effect of Lumbricus protein on the phenotypic transformation of corporal cavernosum smooth muscle cells(CCSMC)and erectile function in diabetic erectile dysfunction(DMED)rats.Methods Sixty male SD rats with normal erectile function were randomly divided into a blank group,a model group,a Sildelafil group(5 mg·kg-1),and a Lumbricus protein low-,medium-,and high-dose group(45,90,and 180 mg·kg-1),with 10 rats in each group.The diabetic rat model was established by intraperitoneal injection of Streptozotocin(STZ,50 mg·kg-1)combined with high-fat feed feeding;after 8 weeks,the DMED rat model was prepared by neck injection of Apomorphine(APO,100 μg·kg-1).After successful modeling,the rats were administered with a dose of Apomorphine by gavage once a day for 4 weeks.The blood glucose levels and body mass of rats in each group were measured before modeling,on the third day of modeling,and after 4 weeks of drug administration.The intracavernous pressure(ICP)and carotid artery pressure(MAP)were measured by multi-channel physiological recorder,and the ICP/MAP ratio was calculated.The expressions of contractile markers α-smooth muscle actin(α-SMA),smooth muscle myosin heavy chain(SMMHC)and synthetic markers Collagen I and osteopontin(OPN)in corpus cavernosum were detected by immunohistochemistry.The mRNA expression levels of α-SMA,SMMHC and Collagen I in corpus cavernosum were detected by RT-PCR.The protein expression levels of α-SMA,Desmin,Collagen I and OPN in corpus cavernosum were detected by Western Blot.Results Compared with the blank group,the blood glucose levels of the rats in the model group were significantly increased on the third day of modeling and after 4 weeks of administration(P<0.01),and the body mass was significantly decreased after 4 weeks of administration(P<0.01).ICP and ICP/MAP ratio were significantly decreased(P<0.01).The protein expression levels of α-SMA,SMMHC and Desmin in penile corpus cavernosum were significantly decreased(P<0.01),and the protein expression levels of Collagen I and OPN were significantly increased(P<0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly decreased(P<0.01),and the mRNA expression level of Collagen I was significantly increased(P<0.01).Compared with the model group,there was no significant change in blood glucose and body mass of rats in the administration group(P>0.05).ICP and ICP/MAP ratio were significantly increased(P<0.01).The expression levels of α-SMA,SMMHC and Desmin in corpus cavernosum were significantly increased(P<0.01),while the expression levels of Collagen I and OPN were significantly decreased(P<0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly increased(P<0.01),and the mRNA expression level of Collagen I was significantly decreased(P<0.01).Conclusion Lumbricus protein can improve the erectile function of DMED rats,and its mechanism may be related to the inhibition of CCSMC from'contractile'to'synthetic(proliferative)'transformation.
5.Exploration on the TCM Pathogenesis of Pulmonary Fibrosis Based on the Theory of"Lung Connecting to Large Intestine"
Yawei DONG ; Zhongbo ZHU ; Fan YANG ; Quan MA ; Hongmei LI ; Yanmei ZHANG ; Lanlan HE ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):19-23
Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".
6.Effects of acute lung injury on apoptosis in rat splenic T cells and the interventional effect of Yifei Jianpi formula
Yujie YANG ; Zhongbo ZHU ; Yanmei ZHANG ; Xiping LIU ; Xuhui ZHANG ; Zhiming ZHANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(9):1160-1170
Objective To observe splenic T cell apoptosis and XIAP-associated factor 1(XAF1),FAS,and tumor necrosis factor(TNF)-α protein expression levels in rats with acute lung injury(ALI),and to determine their roles in the protective effect of Yifei Jianpi formula.Methods Sixty male specific pathogen-free SD rats were divided randomly into blank,model,positive control,and high-,medium-,and low-dose Yifei Jianpi formula groups.Rats in the positive control group were given 0.5 g/kg dexamethasone by gavage,and rats in the high-,medium-,and low-dose Yifei Jianpi formula groups were given 12,6,and 3 g/kg Yifei Jianpi formula by gavage,respectively.Rats in the model and blank groups were given equal amounts of saline by gavage.All medications were administered once a day for 14 days.Lung function testing was carried out in all rats.We observed the imaging characteristics of the lungs and changes in the organ index and lung tissue wet/dry weight(W/D)in each group,and detected the pathological changes in lung tissues by hematoxylin-eosin staining.Splenic T-cell subpopulations(CD4+/CD8+)and apoptosis of splenic T-cells were detected by flow cytometry and XAF1,FAS,and TNF-α protein expression levels in the spleen were detected by Western Blot.Results Rats in the model group showed reduced lung function,decreased spleen and thymus organ indexes,and significantly higher W/D of lung tissue(P<0.01).In addition,they had inflammatory exudation and alveolar rupture in the lung tissue,accompanied by thickening of the lung texture and large areas of ground-glass shadows,with a significant decrease in T-cell subsets(CD4+/CD8+)and significant increases in XAF1,FAS,and TNF-α proteins,and in the rate of T-cell apoptosis(P<0.01).Yifei Jianpi formula significantly reduced the W/D spleen of rat lung tissues,significantly increased the thymus organ index(P<0.05,P<0.01)and the T-cell subpopulation(CD4+/CD8+),and significantly decreased the protein expression levels of XAF1,FAS,and TNF-α,and the T-cell apoptosis rate(P<0.05,P<0.01).Conclusions ALI induced up-regulation of XAF1,FAS,and TNF-α protein expression and T-cell apoptosis in the spleen of rats,and Yifei Jianpi formula may protect against ALI by down-regulating these factors.
7.Clinical features and stroke etiology in 10 patients with bilateral middle cerebellar peduncle infarctions: a preliminary study
Jiwei JIANG ; Ya'ou LIU ; Xiping GONG ; Linlin WANG ; Wenyi LI ; Xinying ZOU ; Junjie LI ; Jun XU
Chinese Journal of Neurology 2023;56(6):654-660
Objective:To characterize clinical and neuroimaging features, etiologies, and mechanisms of bilateral middle cerebellar peduncle (MCP) infarctions.Methods:Consecutive patients with bilateral MCP infarctions treated in the Beijing Tiantan Hospital, Capital Medical University between January 1, 2020 and April 30, 2022 were enrolled in this retrospective study. The demographic data, vascular risk factors, clincial manifestations and the National Institutes of Health Stroke Scale (NIHSS) scores were collected. Brain diffusion-weighted imaging was used to assess the regions of cerebral infarction, and the extracranial and intracranial segments of the vertebrobasilar artery were evaluated using magnetic resonance angiography, or computed tomography angiography. The stroke etiology and underlying mechanism were evaluated according to the Chinese Ischemic Stroke Subclassification.Results:Ten patients with bilateral MCP infarctions (8 men and 2 women) were analyzed ultimately. The onset age were 51.0-86.0 (64.8±11.4) years. NIHSS scores were 2.0-12.0 (4.9±2.9) points at admission. All patients had vascular risk factors, most of which were hypertension (10 cases) and dyslipoproteinemia (8 cases). The most common clinical manifestations were vertigo (10 cases), followed by ataxia (9 cases) and dysarthria (8 cases). Four cases were isolated bilateral MCP infarctions, while 6 patients were combined with other vertebrobasilar artery infarctions, 4 of which were combined with cerebellar hemisphere infarctions, consistent with the clinical symptoms. The etiology in all patients was large atherosclerosis (severe stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery; 9 cases). Five patients were classified as hypoperfusion/impaired emboli clearance, while 4 patients were considered as artery-to-artery embolism, and 1 was considered as the parent artery (plaque or thrombosis) occluding penetrating artery.Conclusions:Bilateral MCP infarctions are an extremely rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria. Cerebral infarction can be isolated or often combined with cerebellar hemisphere infarction. The etiology was mostly stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery.
8.Death of hospitalized neonates of different gestational age in Shaanxi Province: a multi-center survey
Yunfan YANG ; Juan ZHANG ; Juanjuan ZHANG ; Xiping YU ; Zhankui LI ; Heqin LI ; Wenping SONG ; Zengfang LIU ; Guanshan YANG ; Huanli GUO
Chinese Journal of Perinatal Medicine 2023;26(5):398-405
Objective:To investigate the current status of hospitalized neonatal death of different gestational ages in Shaanxi Province.Methods:All neonatal deaths in six hospitals in Shaanxi Province from 2016 to 2020 were retrospectively analyzed, and the differences in perinatal complications, the causes of death, and the age at death were compared using Chi-square (or Fisher's exact ) test. Results:(1) Totally, 220 488 neonates were delivered in the obstetric department of the six hospitals during the study period; 71 782 out of them were admitted to the neonatal department. While 424 neonatal death was reported, giving the total hospitalized neonates mortality rate of 5.5‰ (394/71 782), which included 152 deaths of transferred patients ( n=9 103, 16.7‰), 226 premature (53.3%), 196 term (46.2%), and two post-term infants (0.5%). (2) Among mothers of dead neonates, 73.6% were found to have at least one perinatal complication. The most common one was fetal distress (146 cases, 34.4%), followed by gestational diabetes mellitus (113 cases, 26.7%), amniotic fluid abnormalities ( n=73, 17.2%), maternal infectious diseases ( n=71, 16.8%), and hypertensive disorders in pregnancy (HDP) ( n=52, 12.3%). The lower the gestational age, the higher the proportion of multiple pregnancies and assisted reproduction technology applied (Fisher exact test, P<0.05). On the contrary, the higher the gestational age, the higher the cesarean section rate ( χ 2=26.69, P<0.001). HDP was more likely to occur in the gestational age of 28-31 +6 and 32-34 +6 weeks ( χ 2=37.16, P<0.001), and amniotic fluid abnormalities were more likely to occur in those over 37 weeks ( χ 2=27.47, P<0.001). (3) The five leading causes of neonatal death were neonatal respiratory distress syndrome (NRDS, n=100, 23.6%), neonatal asphyxia ( n=88, 20.8%), maternal infectious diseases ( n=80, 18.9%), and birth defects ( n=54, 12.7%), and pulmonary hemorrhage ( n=22, 5.2%). The first three causes of death in term and post-term infants were neonatal asphyxia ( n=65, 32.8%), birth defects ( n=42, 21.2%), and infectious diseases ( n=26, 13.1%). NRDS ( n=83, 36.7%), infectious diseases ( n=54, 23.9%), and neonatal asphyxia ( n=23, 10.2%) were the three leading causes of death of premature babies. (4) Out of the 326 (76.9%) neonatal deaths within seven days after birth, 162 (38.2%) died within 24 h after birth and 164 cases (38.7%) between one to seven days after birth. Conclusions:Most neonatal deaths occurred among preterm ones and within seven days after birth, whose mothers suffered perinatal complications. The causes of neonatal death vary among different gestational age groups.
9. Involvement of autophagy in iron ion regulation promotes ferroptosis in cells undergoing intestinal ischemia-reperfusion injury
Jingyu ZHANG ; Yihan WANG ; Jun LI ; Ping JIN ; Yingbin WANG ; Jieting LIU ; Xiping SHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(1):36-41
AIM: To investigate the effect of autophagy on cell ferroptosis in intestinal ischemia-reperfusion injury. METHODS: Twenty-four SPF grade Wistar rats weighing 200-220 g were divided into 4 groups (n = 6): sham operation group (sham group), ischemia group (I group), ischemia-reperfusion group (I/R group),and ischemia-reperfusion + autophagy inhibitor group (I/R + 3-MA group). The ischemia model was established by clamping the superior mesenteric artery for 1 hour, and the intestinal ischemia-reperfusion injury model was established by reperfusion for 2 hours. HE staining was used to observe the pathological changes of intestinal mucosa and Chiu score under light microscope. Fe
10.Four-in-one surgery for treatment of Crawford Ⅳ congenital pseudarthrosis of the tibia in children
Chinese Journal of Orthopaedic Trauma 2023;25(11):1003-1007
Objective:To explore the clinical efficacy of 4-in-1 surgery in the treatment of Crawford Ⅳ congenital pseudarthrosis of the tibia (CPT) in children.Methods:A retrospective study was conducted to analyze the clinical data of 86 patients with Crawford Ⅳ CPT who had been treated by 4-in-1 surgery at Orthopedic Department, Hunan Children's Hospital from January 2013 to December 2017. There were 47 boys and 39 girls, with an age of (40.7 ± 9.7) months at the time of surgery. Of them, 63 were complicated with type I neurofibromatosis. The 4-in-1 surgery consisted of resection of the tibial pseudarthrosis and surrounding hamartoma-like tissue, internal fixation with tibial intramedullary rod, grafting with wrapped autologous iliac bone, and Ilizarov external fixation. Their bone union, postoperative complications, and follow-up results were recorded.Results:The mean postoperative follow-up time was (80.1 ± 12.4) months for this cohort. The initial bone union rate was 96.5% (83/86), and the initial bone union time (4.8 ± 0.7) months. The last follow-up revealed 20 re-fractures, 15 cases of leg length discrepancy (longer tibia on the affected side in 5 ones and longer tibia on the healthy side in 10 ones), 10 cases of proximal tibial valgus, 12 cases of ankle valgus, 9 cases of bone bridge formation of the distal tibial epiphyseal plate, 10 cases of Ilizarov pin infection, and 2 cases of tibial osteomyelitis. Ankle stiffness occurred in 35 cases, and deviation of the tibial intramedullary rod from the center of the tibial medullary cavity in 60 cases, of which the intramedullary rod had to be removed in 20 because the rod protruded the tibial bone cortex. At the last follow-up, there were 15 cases of skeletal maturity and 71 cases of immature skeleton.Conclusions:In the treatment of Crawford Ⅳ CPT in children, the 4-in-1 surgery can lead to a high rate of initial bone union and definite primary clinical efficacy, but further improvements are necessary because postoperative complications are numerous.

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