1.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
2.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
3.Mortality, morbidity, and care practices for 1750 very low birth weight infants, 2016-2021
Yang HE ; Meng ZHANG ; Jun TANG ; Wanxiu LIU ; Yong HU ; Jing SHI ; Hua WANG ; Tao XIONG ; Li ZHANG ; Junjie YING ; Dezhi MU
Chinese Medical Journal 2024;137(20):2452-2460
Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.
4.Analysis of influencing factors of early femoral head necrosis after femoral neck fracture and construction of nomo-gram prediction model
Zhi-Qiang FU ; Wei WANG ; Fei-Xiong HE ; Sheng-Kun HONG ; Wei-Jun ZHOU
China Journal of Orthopaedics and Traumatology 2024;37(7):694-699
Objective To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation,and to establish a nomogram prediction model.Methods A total of 167 patients with femoral neck fracture from Jan-uary 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period.There were 21 males and 17 females in the necrosis group,aged from 33 to 72 years old,with an average of(53.49±10.96)years old,and the time from injury to operation ranged from 40 to 67 hours,with average time of(53.46±7.23)hours.There were 72 males and 57 females in the non-necrosis group,aged from 18 to 83 years,with an average of(52.78±12.55)years old,and the time from injury to operation was 18 to 65 hours,with an aver-age time of(39.88±7.79)hours.The potential influencing factors,including patient gender,diabetes mellitus,hypertension,chronic liver disease,posterior inclination angle of the femoral head,operation mode,fracture displacement,fracture line loca-tion,preoperative braking traction,screw arrangement mode,reduction quality,age,body mass index(BMI),and injury to operation time were subjected to single factor analysis.Logistic multivariate regression analysis was conducted for factors with a significance level of P<0.05.Results The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76%.The following factors were identified as independent risk factors for early postoperative femoral head necrosis in pa-tients with femoral neck fractures:coexisting diabetes[OR=5.139,95%CI(1.405,18.793),P=0.013],displaced fracture[OR=3.723,95%CI(1.105,12.541),P=0.034],preoperative immobilization[OR=3.444,95%CI(1.038,11.427),P=0.043],quality of reduction[OR=3.524,95%CI(1.676,7.411),P=0.001],and time from injury to surgery[OR=1.270,95%CI(1.154,1.399),P=0.000].The Hosmer-Lemeshow goodness-of-fit test(x2=3.951,P=0.862),the area under the receiver operator characteristic(ROC)curve was 0.944[P<0.001,95%CI(0.903,0.987)],with a sensitivity of 89.50%,the specificity was 88.40%,the maxi-mum Youden index was 0.779,and the overall trend of the model correction curve was close to the ideal curve.Model regres-sion equation was Z=1.637 × diabetes+1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduc-tion quality+0.239 ×injury to operation time-18.310.Conclusion The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors.The risk early warning model established according to the factors has good predictive efficacy.
5.Analysis of the effect of butorphanol combined with parecoxib sodium on patient-controlled intravenous analgesia after uvulo-palato-pharyngo-plasty
Lang XIONG ; Yuan-Yuan WEI ; Zhi-Jun YANG
Journal of Regional Anatomy and Operative Surgery 2024;33(11):941-944
Objective To investigate the effect of butorphanol combined with parecoxib sodium on patient-controlled intravenous analgesia(PCIA)after uvulo-palato-pharyngo-plasty(UPPP).Methods Eighty patients who were admitted to our hospital from October 2021 to May 2023 and planned to receive UPPP were collected,and they were randomly assigned to the paroxicib sodium group(D group),the butorphanol low-dose group(B1 group),the butorphanol medium dose group(B2 group),and the butorphanol high-dose group(B3 group),with 20 cases in each group.Patients in the D group received 40 mg of paroxycoxib sodium with 0.9% sodium chloride injection for analgesia,and patients in the B1 group,the B2 group,and the B3 group were combined with 3.0 μg·kg-1·h-1,4.0 μg·kg-1·h-1,and 5.0 μg·kg-1·h-1 of butorphanol respectively on the basis of D group.The heart rate and mean arterial pressure before PCIA and 2 hours,12 hours,24 hours,and 48 hours after PCIA were compared among the four groups;the pain visual analogue scale(VAS)score,Ramsay score 2 hours,12 hours,24 hours,and 48 hours after PCIA were compared among the four groups;the number of PCIA compression,and incidence of adverse reactions were recorded.Results There was no statistically significant difference in the heart rate or mean arterial pressure before PCIA and 2 hours,12 hours,24 hours,and 48 hours after PCIA among the four groups(P>0.05).Compared with the D group,the VAS scores 2 hours,12 hours,24 hours,and 48 hours after PCIA of the B1,B2,and B3 groups significantly decreased(P<0.05),and the higher the dose of butorphanol,the lower the VAS score(P<0.05).Compared with the D group,the Ramsay scores 2 hours,12 hours,24 hours,and 48 hours after PCIA of the B1,B2,and B3 groups obviously increased(P<0.05),and the higher the dose of butorphanol,the higher the Ramsay score(P<0.05).The total incidence of adverse reactions in the B3 group was obviously higher than that in the D group,the B1 group,and the B2 group(P<0.05).Compared with the D group,patients in the B1,B2,and B3 groups had significantly fewer PCIA compressions(P<0.05),and the higher the dose of butorphanol,the fewer the PCIA compressions(P<0.05).Conclusion The effect of butorphanol combined with parecoxib sodium in PCIA after UPPP is better,and combined with 4.0 μg·kg-1·h-1 parecoxib sodium has more significant analgesic effect and higher safety.
6.Mechanism about LMP1 of EB Virus Promoting Plasma Blast Diffe-rentiation of DLBCL Cell via mTORC1
Jing-Jing GAO ; Xiong-Peng ZHU ; Ming-Quan WANG ; Xing-Zhi LIN ; Yan-Ling ZHUANG ; Hong-Jun LIN
Journal of Experimental Hematology 2024;32(1):219-224
Objective:To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway.Methods:The expression levels of LMP1 protein,CD38 and the phosphorylation levels of p70S6K in EBV+and EBV-DLBCL cell lines were detected by Western blot.Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi.The expression of LMP1 gene was verified by RT-qPCR.The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot.Results:Compared with EBV-DLBCL cells,the expression of LMP1 was detected on EBV+DLBCL cells(P=0.0008),EBV+DLBCL cells had higher phosphorylation levels of p70S6K(P=0.0072)and expression levels of CD38(P=0.0091).Compared with vector group,the cells of LMP1OE group had higher expression levels of LMP1 and CD38(P=0.0353;P<0.0001),meanwhile molecular p70S6K was phosphorylated much more(P=0.0065);expression of LMP1 mRNA was verified(P<0.0001).Compared with si-NC group,expression level of LMP1 protein(P=0.0129)was not detected and phosphorylated p70S6K disappeared of LMP1KO group(P=0.0228);meanwhile,expression of CD38 decreased,although there was no significant difference(P=0.2377).Conclusion:LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.
7.Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor
Jia-Ying LEI ; Yang LI ; Chun-Mou LI ; Xi-Lin XIONG ; Chu-Chu FENG ; Wen-Jun WENG ; Xiao-Min PENG ; Dun-Hua ZHOU ; Ke HUANG
Journal of Experimental Hematology 2024;32(2):445-449
Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P<0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.
8.Development and validation of an Assessment Scale of Proactive Health Behavior Ability for the Disabled Elderly in Nursing Homes
Yangli OU ; Xiaoyan LIAO ; Ying PENG ; Hong ZHANG ; Shaohua YIN ; Liyu CHEN ; Xue XIONG ; Xiuli YU ; Lifang TONG ; Yan XIE ; Dan HUO ; Jun SHEN
Chinese Journal of Nursing 2024;59(21):2579-2586
Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992%,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.
9.Research progress of aging-related biomarkers
Hongmei ZHANG ; Jun WEI ; Zhenyu GAO ; Junjie WU ; Xiong XIAO
Chinese Journal of Geriatrics 2024;43(6):668-674
Aging has become an increasingly important topic in the field of geriatrics, with the exploration of aging-related biomarkers providing a foundation for interventions aimed at delaying and reversing aging.Over the years, numerous biomarkers have been developed at both the cellular level(aging mechanisms, histology)and individual level(composite biomarkers, functional biomarkers).This article systematically discusses the characteristics and application scenarios of significant biomarkers at these two levels, and also outlines comparative studies conducted on aging biomarkers.Future research should consider synthesizing multidimensional aging biomarkers at all levels to achieve a more accurate and reliable assessment of aging.Furthermore, there is great potential for further exploration of aging biomarkers through the analysis of histologic data.
10.Mechanism of icariin inhibiting the proliferation of human prostate cancer PC-3 cells:An exploration based on cell metabolomics
Tao WANG ; Wei WANG ; Wen-Jun XIONG ; Zi-Jing ZHANG ; Fei WANG ; Yao-Hui PENG ; Yan CHEN ; Hai-Ping ZENG ; Li-Jie LUO
National Journal of Andrology 2024;30(11):963-973
Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

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