Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

Objective To explore the interventional mechanism of Bufei Yishen formula on chronic obstructive pulmonary disease from pathway level.Methods Macrophage inflammatory model was established by LPS stimulation.Based on gene set enrichment analysis(GSEA)method,macrophage inflammation related pathways were screened,and normalized enrichment score(NES)was used to identify pathways that were reversed by traditional Chinese medicine treatment,revealing the interventional mechanism of Bufei Yishen formula and its compatibility.Results The NES of Bufei Yishen formula was-1377.23,among which the NES of Bushen compatibility was-485.07,that of Huoxue was-351.86,Huatan was-303.71,and Yiqi was-236.59.There were 213 significantly disturbed pathways reversed after the intervention of Bufei Yishen formula,among which there were 184 reversed pathways for Huoxue compatibility,147 reversed pathways for Bushen,134 reversed pathways for Huatan,133 reversed pathways for Yiqi,and the reversal rate was 75.41%,60.25%,54.92%,54.51%,respectively.90 pathways,including TGF-β production,were significantly reversed in the four compatibilities.Positive regulation of cytokine production involved in inflammatory response etc were specifically reversed pathways for compatibility.Conclusion The intensity of Bufei Yishen formula that reversed macrophage-inflammatory related pathways was in order of Bushen,Huoxue,Huatan and Yiqi compatibility.And the number of pathways that could be reversed by the compatibility of Bufei Yishen formula was Huoxue,Bushen,Huatan and Yiqi.Bufei Yishen formula could regulate the common and specific reversal pathways of the compatibilities to intervene the inflammatory response.

AIM:To establish a mouse model of pulmonary fibrosis induced by multiple intratracheal instilla-tions of bleomycin(BLM).METHODS:C57BL/6J mice were randomly divided into five groups:control group(n=5),multiple high-dose BLM(BLM-MH)group(n=10),multiple medium-dose BLM(BLM-MM)group(n=8),multiple low-dose BLM(BLM-ML)group(n=7),and single medium-dose BLM(BLM-SM)group(n=6).The pulmonary fibrosis mod-el was induced by single or multiple intratracheal instillations of BLM.Survival curves were plotted at day 56,and lung tis-sue was collected for lung coefficient calculation.Pathological changes in lung tissue were assessed using hematoxylin-eo-sin(H&E)staining and Masson staining.Indicators of lung fibrosis,such as hydroxyproline(HYP),were measured.Dif-ferentially expressed genes in patients with IPF were screened using the GEO database,and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed to identify pathways associated with IPF.Western blot was used to detect changes in these pathways in the lung tissues of the model mice.RESULTS:The survival rates were 50%in the BLM-MH group and 87.5%in the BLM-MM group,with no deaths in other groups.Compared with the control group,the BLM-MH and BLM-MM groups showed significantly increased lung coefficients(P＜0.05),lung tissue dam-age,inflammation levels,degree of pulmonary fibrosis(P＜0.05 or P＜0.01),and HYP content.The BLM-MH and BLM-MM groups,compared with the BLM-SM group,showed significantly elevated levels of inflammation,fibrosis,and HYP content(P＜0.05 or P＜0.01).GEO database and KEGG enrichment analysis revealed that the extracellular matrix-recep-tor interaction pathway(ECM-RIP)may be involved in IPF development.The expression levels of ECM-RIP pathway-re-lated proteins,such as phosphorylated focal adhesion kinase(p-FAK)and phosphorylated Src protein(p-Src),were in-creased in the lung tissues of the model mice compared with the control group.Compared with the BLM-SM group,the BLM-MH group exhibited significant increases in the protein levels of p-FAK and p-Src in the lung tissue(P＜0.05).CONCLUSION:The murine model of pulmonary fibrosis established through repeated intratracheal instillations of BLM effectively mimics the pathological characteristics of the disease,providing a valuable experimental model for the investiga-tion of idiopathic pulmonary fibrosis pathogenesis and for the development of therapeutic agents.

AIM:To establish a mouse model of pulmonary fibrosis induced by multiple intratracheal instilla-tions of bleomycin(BLM).METHODS:C57BL/6J mice were randomly divided into five groups:control group(n=5),multiple high-dose BLM(BLM-MH)group(n=10),multiple medium-dose BLM(BLM-MM)group(n=8),multiple low-dose BLM(BLM-ML)group(n=7),and single medium-dose BLM(BLM-SM)group(n=6).The pulmonary fibrosis mod-el was induced by single or multiple intratracheal instillations of BLM.Survival curves were plotted at day 56,and lung tis-sue was collected for lung coefficient calculation.Pathological changes in lung tissue were assessed using hematoxylin-eo-sin(H&E)staining and Masson staining.Indicators of lung fibrosis,such as hydroxyproline(HYP),were measured.Dif-ferentially expressed genes in patients with IPF were screened using the GEO database,and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed to identify pathways associated with IPF.Western blot was used to detect changes in these pathways in the lung tissues of the model mice.RESULTS:The survival rates were 50%in the BLM-MH group and 87.5%in the BLM-MM group,with no deaths in other groups.Compared with the control group,the BLM-MH and BLM-MM groups showed significantly increased lung coefficients(P＜0.05),lung tissue dam-age,inflammation levels,degree of pulmonary fibrosis(P＜0.05 or P＜0.01),and HYP content.The BLM-MH and BLM-MM groups,compared with the BLM-SM group,showed significantly elevated levels of inflammation,fibrosis,and HYP content(P＜0.05 or P＜0.01).GEO database and KEGG enrichment analysis revealed that the extracellular matrix-recep-tor interaction pathway(ECM-RIP)may be involved in IPF development.The expression levels of ECM-RIP pathway-re-lated proteins,such as phosphorylated focal adhesion kinase(p-FAK)and phosphorylated Src protein(p-Src),were in-creased in the lung tissues of the model mice compared with the control group.Compared with the BLM-SM group,the BLM-MH group exhibited significant increases in the protein levels of p-FAK and p-Src in the lung tissue(P＜0.05).CONCLUSION:The murine model of pulmonary fibrosis established through repeated intratracheal instillations of BLM effectively mimics the pathological characteristics of the disease,providing a valuable experimental model for the investiga-tion of idiopathic pulmonary fibrosis pathogenesis and for the development of therapeutic agents.

Objective:To compare clinical effects of the open versus closed high tibial osteotomy on knee osteoarthritis.Methods:A total of 100 patients with knee osteoarthritis admitted to our hospital from May 2018 to May 2019 were included.They were randomly divided into groups A and B(n=50, each group)according to the principle of random and double blind.Patients in group A received the medial opening high tibial osteotomy, and group B were treated with lateral closed high tibial osteotomy.The changes in the Lysholm knee score, hospital for special surgery(HSS)knee score and complications were compared between the two groups before and 1 year after surgery.The correction angle, the change of patella height before and after operation, and the change of posterior slope of tibial plateau were compared between the two groups.Results:Before and after treatment, Lysholm scores were(63.51±5.47)and(90.98±5.84)( t=24.275, P=0.000), and HSS scores were(51.85±4.68)and(88.64±5.87)( t=34.652, P=0.000). Lysholm scores were(62.98±6.14)and(91.52±6.54 9)( t=22.497, P=0.000), and HSS scores were(52.05±5.16)and(89.54±5.15)( t=36.362, P=0.000)in group A and B, .After treatment, all index were significantly improved in the two groups, but there was no statistical difference between the two groups( P>0.05). In group A, the posterior slope of tibial plateau were(8.75±1.48)° and(10.25±1.65)°( t=4.785, P=0.000)and the patellar height was(0.890±0.031)and(0.898±0.032)( t=1.270, P=0.207)before and after treatment.Before and after treatment in group B, the posterior slope of tibial plateau were(8.69±1.53)° and(5.26±1.21)°( t=12.434, P=0.000)and the patellar height were(0.889±0.047)and(0.821±0.039)( t=7.873, P=0.000). The correction angle, posterior slope of tibial plateau and patella height were significantly improved after treatment in the two groups.While, the decreases of posterior slope of tibial plateau and patella height were better in the group B than in the group A( P<0.05). There was no significant difference in the incidence of complications between the two groups( P>0.05). Conclusions:For treatment of knee osteoarthritis patients, the medial opening high tibial osteotomy and lateral closed high tibial osteotomy have the same exact effect and high safety, but the two methods have their own advantages and disadvantages in clinical treatment.And the appropriate surgical treatment can be selected according to the characteristics of patients.

OBJECTIVETo identify a rare α-thalassemia gene mutation in a family from south China and perform a pedigree analysis and genetic diagnosis of hemoglobin H (HbH) disease caused by this mutation.

METHODSPeripheral blood samples were collected from the family members for analysis of the hematological phenotype and routine test of thalassemia genes. DNA sequencing was carried out for samples that showed genotype and phenotype inconsistency.

RESULTSA rare α-thalassemia *92A>G gene mutation was detected within this family. The proband and his sister were confirmed to have non-deletional HbH disease with α--/αα genotype. The proband's brother was confirmed to have an α-thalassemia trait with the genotype of -α/αα. The proband's father was identified as an α-thalassemia silent carrier with the genotype of αα/αα.

CONCLUSIONA rare α-thalassemia *92A>G gene mutation was identified for first time in south China. The description of the basic phenotypic characteristics of α-thalassemia trait and silent carrier caused by this mutation enriches the α-thalassemia gene mutation spectrum in Chinese population and helps in population screening, clinical molecular diagnosis and genetic counseling.

Objective To explore surgical techniques and clinical effects of arthroscopic absorbable interference screw fixation and four-stranded hamstring tendon autograft for the reconstruction of anterior cruciate ligament (ACL). Methods Forty-two patients with rupture of the ACL were operated on by arthroscopic four-stranded hamstring tendons autograft reconstruction using SR-PLLA absorbable screw fixation. Results Follow-up for 3～22 months (mean, 11 4 months) in all 42 patients showed normal motion range of knee joint. Postoperative Lachman test revealed ≤1+ in 37 patients, 2+ in 4 patients and 3+ in 1 patient. All patients showed an absent pivot shift. Postoperative Lysholm score was 89 7?9 6 points, which had increased significantly as compared with the preoperative score (49 4?9 1 points; t =2 12, P =0 038). Postoperative Tegner activity grading scale was 5 3?1 1 points, which was significantly higher than the preoperative one (2 3?0 7 points; t =4 13, P =0 008). MRI examination at first postoperative year showed that absorbable interference screws were partly absorbed in 29 patients,and reconstructed ligaments were in good position and normal in shape in 27 patients.The tendon grafts were anchored on the femur a little too more to the front side in 2 patients, and on the tibia a little too more to the front side in 3 patients, with slight impingement phenomena. Conclusions In ACL reconstruction, four-stranded hamstring tendon is an ideal graft material and absorbable interference screw is optimal for internal fixation.