Objective To analyze the related factors of prognosis in patients with primary Sjogren’s syndrome (SS) complicated with renal damage, and to provide reference for clinical development of personalized prevention and treatment measures. Methods A total of 508 patients with primary SS complicated with renal damage in the First Affiliated Hospital of Xinjiang Medical University from February 2020 to February 2022 were enrolled as study subjects. According to the prognosis status within 3 years, the enrolled patients were divided into good prognosis group (n=426) and poor prognosis group (n=82). Univariate and logistic multivariate regression analyses were adopted to analyze the influencing factors of poor prognosis. Results There were significant differences in hypertension, anemia, renal interstitial chronicity grading, and levels of globulin (GLO), immunoglobulin G (IgG) and hemoglobin between the two groups (P<0.05). Logistic multivariate analysis showed that concurrent hypertension, anemia, increased grade of renal interstitial chronicity, and elevated GLO and IgG levels were risk factors of poor prognosis in patients with primary SS complicated with renal damage, while hemoglobin level was a protective factor (OR: 1.962, 95%CI: 1.056-3.645; OR: 2.467, 95%CI: 1.153-5.278; OR: 17.796, 95%CI: 5.157-61.419; OR: 3.655, 95%CI: 1.812-7.372; OR: 5.732, 95%CI: 2.632-12.480; OR: 0.325, 95%CI: 0.165-0.640, P<0.05). Conclusion Patients with primary SS complicated with renal damage have a higher risk of poor prognosis, which is affected by factors such as hypertension, anemia, and GLO, IgG and hemoglobin levels. Clinically, it is necessary to take active prevention and treatment measures to improve the prognosis of patients.

Osteoporosis can be induced by various factors including prolonged glucocorticoid usage, diminished estrogen levels, secondary hyperparathyroidism, and alterations in the microenvironment of bone tissue. The bone metabolism imbalance(osteogenic-lipogenic imbalance) plays a crucial role in the development of osteoporosis. This imbalance is primarily driven by an increase in the differentiation of bone marrow mesenchymal stem cells into adipocytes and a decrease in their differentiation into osteoblasts, thus forming the core of the osteogenic-lipogenic imbalance observed in osteoporosis. The bone morphogenesis protein(BMP) plays a crucial role in the regulation of the osteogenic-lipid balance in osteoporosis. This regulatory function is accomplished through both the Smad-dependent and Smad-independent pathways. This review centers on the Smad-dependent and Smad-independent pathways facilitated by BMP, offering a comprehensive overview of the potential mechanisms through which BMP-2, 4, 6, 7, and 9 contribute to the regulation of osteogenesis and lipid metabolism in osteoporosis via these pathways. In order to present novel insights for the identification of efficacious targets for clinical anti-osteoporosis medications.

Objective To investigate the mechanism of Ganmao Qingre Pills(GQP)against lung injury based on network pharmacology,molecular docking and in vivo experiments.Methods The potential targets of GQP in the treatment of lung injury were screened through traditional Chinese medicine systems pharmacology database and analysis platform(TCM-SP)and Genecards.A"Chinese medicine-active ingredients-targets"network was constructed using Cytoscape 3.9.0 software,then gene ontology(GO)function and Kyoto encyclopaedia of genes and genomes(KEGG)pathway enrichment analysis for potential targets were conducted using a bioinformatics cloud platform.We established a protein-protein interaction(PPI)network,which was intersected with"Chinese medicine-active ingredients-targets"network to obtain core targets.The molecular docking between key target proteins and active ingredients was performed.The effect of GQP on these key target proteins was verified by using a mouse model of lung injury.Results A total of 707 targets for the treatment of lung injury by GQP were identified,corresponding to 107 active ingredients in 11 Chinese medicines.It was found that GQP might regulate targets such as PTGS1,AR,and ACHE through active ingredients including stigmasterol,luteolin,and acacetin using the"Chinese medicine-active ingredients-targets"network analysis.Core targets such as SRC,EGFR,and STAT3 were discovered by using the PPI network.Key target proteins,including CDK1,CDK2,EGFR,ESR1 and SRC,were screened through the intersection analysis of the PPI network and"Chinese medicine-active ingredients-targets"network.Molecular docking study showed that stigmasterol,luteolin and acacetin had good binding effects with CDK1,CDK2,EGFR,ESR1,and SRC,respectively.In vivo experiments revealed that GQP dose-dependently attenuated lung injury and inflammatory infiltration,reduced the release of pro-inflammatory factors TNF-α,IL-1β and IL-6,increased the expression of CDK1 and CDK2,and decreased the expression of EGFR,ESR1 and SRC in lung injury mice.Conclusion The therapeutic effect of GQP against lung injury may be achieved through interaction of key active ingredients(stigmasterol,luteolin,and acacetin)and key target proteins(CDK1,CDK2,EGFR,ESR1,SRC),and regulation of key signaling pathways such as neuroactive ligand-receptor interactions,cancer pathways,and calcium signaling pathways.

AIM:Observation of neuroprotective effects of Toddalia asiatica(TA)on cerebral ischemia-reper-fusion injury(CIRI)in rats by investigating the effects and mechanisms of drugs on the polarization of microglia M1/M2 subtype and the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)path-way.METHODS:The modified thread occlusion method was used to establish a rat model of CIRI,and the rats were ran-domly divided into the model group,Toddalia asiatica(1.08 g/kg)group,donepezil hydrochloride(0.45 mg/kg)group,and sham group,with 16 rats in each group.Based on the assessment of neurofunctional changes in each group of rats,HE and Nissl staining were used to observe the pathological changes in brain tissue.TUNEL staining was performed to de-tect neuronal apoptosis,immunohistochemistry was used to detect the expression of M1 microglia marker ionized calcium-binding adapter molecule 1(Iba1),M2 microglia marker arginase 1(Arg1),and TLR4 localization.Western blot was used to detect the expression of microglia polarization proteins and proteins related to TLR4/MyD88/NF-κB pathway in the hippocampus region.RESULTS:Compared with sham group,the model group rats had higher neurological function scores(P＜0.01),and neuronal arrangement in the hippocampus and cortex was loose and disordered,Nissl bodies de-creased,and neuronal apoptosis increased.The numbers of M1 microglia marker Iba1-,M2 microglia marker Arg1-,and TLR4-positive cells were significantly increased.In addition,the protein levels of TLR4,MyD88,p-NF-κB p65,NF-κB p65,p-NF-κB inhibitory factor(p-IκB),Iba1,interleukin-6(IL-6),and Arg1 in the hippocampus were elevated(P＜0.05),while IL-4 and IL-10 expression were decreased(P＜0.01).Compared with model group,the Toddalia asiatica group and Donepezil hydrochloride group showed increased protein expression of Arg1,IL-4 and IL-10(P＜0.05),while the other indicators were decreased(P＜0.05,P＜0.01).CONCLUSION:Toddalia asiatica possesses neuroprotective effects on CIRI rats,which may be attributed to its ability to regulate M1/M2 polarization and inhibit the TLR4/MyD88/NF-κB-mediated inflammatory pathway.

Objective:To explore the application effect of multimodal quantitative rehabilitation exercise in patients with ankylosing spondylitis and to provide reference for patients′ rehabilitation exercise.Methods:The quasi-experimental study method was used to select 78 patients with ankylosing spondylitis admitted to Rheumatology and Immunology Department of First Affiliated Hospital of Xinjiang Medical University from February 2021 to February 2022 as the research objects. The 39 patients admitted from February 2021 to August 2021 as the control group, and 39 patients admitted from September 2021 to February 2022 as the experimental group. The control group adopted conventional rehabilitation exercise program, and the experimental group adopted multimodal quantitative rehabilitation exercise program. The Bath ankylosing spondylitis disease activity index, Bath ankylosing spondylitis function index, inflammatory factors after 6 months of intervention were compared between the two groups.Results:The Bath ankylosing spondylitis disease activity index in the experimental group after 6 months of intervention was (2.35 ± 0.81) points, and that in the control group was (3.47 ± 1.04) points, with a statistically significant difference ( t = 4.02, P<0.05). The Bath ankylosing spondylitis disease activity index in the two groups were analyzed by repeated measurement variance. The differences of time effect, inter group effect and interaction effect were statistically significant ( Fgroup = 11.27, Ftime = 62.05, Finteraction = 5.47, all P<0.05). The Bath ankylosing spondylitis function index in the experimental group after 6 months of intervention was (2.11 ± 0.32) points, and that in the control group was (3.07 ± 0.58) points, with a statistically significant difference ( t = 4.03, P<0.05). The Bath ankylosing spondylitis function index in the two groups were analyzed by repeated measurement variance. The differences in time effect, inter group effect and interaction effect were statistically significant ( Fgroup = 21.44, Ftime = 42.25, Finteraction = 16.67, all P<0.05). After 6 months of intervention, C-reactive protein, interleukin-6, transforming growth factor β, tumor necrosis factor-α were (43.15 ± 2.21) mg/L, (3.28 ± 0.85) mg/L, (41.67 ± 9.04) ng/L, (176.63 ± 20.15) ng/L respectively in the experimental group, and (50.12 ± 1.67) mg/L, (5.27 ± 0.68) mg/L, (48.65 ± 8.96) ng/L, (194.56 ± 19.45) ng/L respectively in the control group. There was a statistically significant difference in the content of inflammatory factors between the two groups ( t values were 2.05-4.45, all P<0.05). Conclusions:Multimodal quantitative rehabilitation exercise can improve the physiological function of ankylosing spondylitis patients′spine, reduce the disease activity of patients, and promote the rehabilitation of patients.

Objective:To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis.Methods:① Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. ② Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting.Results:① Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (μg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×10 9/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients ( n = 20) was significantly higher than that in the non-thrombocytopenia patients ( n = 37; μg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients ( r = -0.340, P = 0.010). ② Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×10 9/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/β-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. Conclusion:PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.

【Objective】 To establish a method for detecting human immunoglobulin Fc function based on surface plasmon resonance technology. 【Methods】 Based on the characteristic that FcγRI can be binded to the Fc segment of IgG, the affinity constant of the sample was detected by surface plasmon resonance, and its Fc function was the KD ratio of the sample to the standard. The method was validated for specificity/specificity, precision and robustness. The method and the pharmacopoeia method were used to detect the Fc function of 30 human immunoglobulins, and the correlation and consistency of the detection results were analyzed. 【Results】 The method validation results showed that this method has strong specificity/specificity (t values were 0.15, 0.22, both P>0.05), good precision (CV value 5.37%~10.69%) and good robustness (CV value 10.06%). The detection results of this method and the pharmacopoeia method have high correlation (r=0.96, P<0.05) and high consistency (Bias-2.060, 95% Limits of Agreement-5.628~1.508). 【Conclusion】 A method for detecting human immunoglobulin Fc function based on surface plasmon resonance has been successfully established.

The high performance liquid chromatography (HPLC) and enzyme-linked immunoassay (ELISA) were used to investigate the changes of collagen and matrix metalloproteinase-1 (MMP-1) in liver, lung and kidney during growth process of mice. The mice from 0 to 18 weeks were used as the research objects. The contents and proportions of hydroxyproline (Hyp), which were used to calculate the collagen contents, in liver, lung and kidney of different weeks were analyzed with HPLC. The contents and activity of MMP-1 in liver, lung and kidney of different weeks were analyzed with ELISA. The results showed that the collagen contents in liver, lung, and kidney were different (Lung(COL)>Kidney(COL)>Liver(COL)), and they all increased first and then decreased with weeks. The collagen contents in liver, lung, and kidney reached the highest level in the ninth (5.52 ng/mg), sixth (54.10 ng/mg) and ninth (19.20 ng/mg) week, respectively. Then it declined slowly from 9 to 18 weeks. The result of ELISA showed that the MMP-1 contents in liver, lung and kidney decreased first and then increased with weeks, and the trend of MMP-1 activity was opposite. It indicated that the increase of collagen contents in the tissues will inhibit the secretion of MMP-1.
Animals ; Collagen ; Kidney ; Liver ; Lung ; Matrix Metalloproteinase 1 ; Matrix Metalloproteinase 2 ; Mice

Objective:To investigate the efficacy and safety of different stents assisted embolization in the treatment of subarachnoid hemorrhage(SAH) caused by V4 dissecting aneurysm of vertebral artery.Methods:The clinical data of 39 patients with spontaneous SAH V4 dissecting aneurysm treated at the Department of Neurosurgery, the Northern Theater General Hospital from January 2016 to June 2019 were analyzed retrospectively.There were 21 males and 18 females, aged (48±17) years(range:35 to 68 years).There were 24 cases of HUNT-HESS grade Ⅰ and 15 cases of grade Ⅱ.Among them, 20 cases were treated with single stent-assisted embolization, 9 cases with multi-stent-assisted embolization, 9 cases with semi-dense mesh-assisted embolization, and 1 case with dense-mesh stent-assisted embolization.The perioperative and postoperative complications, postoperative recurrence were collected.Results:Intraoperative complications included 2 cases of aneurysm rupture and 2 cases of acute thrombosis.All aneurysms were densely packed according to the angiography performed immediately after operation.Postoperative complications included 3 cases of long-term responsible vascular ischemia(modified Rankin score<2). The patients were followed up for 15.1 months(range: 12 to 29 months). At the last follow-up, aneurysms recurrence occured in 10 cases, the recurrence rate was 25.6%(10/39). There were 6 cases of recurrence and 2 cases of complications in 20 cases with single stent-assisted embolization, 3 cases of recurrence and 4 cases of complications in 9 cases with multi-stent-assisted embolization, 1 case of recurrence and 1 case of complications in 9 cases with semi-dense mesh stent.Conclusion:Endovascular treatment is feasible for patients with vertebral artery dissecting aneurysm, and the appropriate surgical method should be selected according to the vascular structure and the location of the aneurysm.