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.

AIM:To observe the neuroprotective effects of total saponins of Trillium tschonoskii Maxim(TST)on rats with vascular dementia(VD)and explore the drug's impact on astrocytes and the Sonic Hedgehog(Shh)pathway as well as its mechanisms of action.METHODS:A rat model of vascular dementia was established by bilateral common carotid artery occlusion.Subsequently,the rats were randomly divided into four groups:donepezil hydrochloride group,TST group,model group,and sham group,with 18 rats in each group.After 5 weeks of gavage,samples were collected.Cognitive function was evaluated by the water maze test.Histopathological changes in brain tissue were examined with HE and Nissl staining.The ultrastructure of astrocytes was analyzed by transmission electron microscopy.The localization and expression of the neuronal nuclear antigen(NeuN),glial fibrillary acidic protein(GFAP),Shh,and glioma-associated oncogene homolog 1(Gli1)were identified using immunohistochemistry.Immunofluorescence was also employed to exam-ine the expression of NeuN and GFAP.Finally,Western blot analysis was used to measure the protein levels of NeuN,GFAP,Shh,Patched 1(Ptch1),Gli1,Bax,Bcl-2,tumor necrosis factor-α(TNF-α),and interleukin-10(IL-10)in the hippocampus.RESULTS:Compared to the sham group,the model rats demonstrated prolonged escape latency,disorga-nized and loosened neuronal arrangement in the hippocampus and cortex,reduced Nissl bodies,and significant neuronal damage.Astrocytes displayed chromatin aggregation,swollen mitochondria with disrupted cristae structures,and swollen endoplasmic reticulum regions.The expression of NeuN,Shh,and Gli1 positive cells significantly decreased,while GFAP positive cells significantly increased.Additionally,the protein levels of NeuN,Shh,Ptch1,Gli1,IL-10,and Bcl-2 in the hippocampus were reduced(P＜0.05),whereas those of GFAP,Bax,and TNF-α were elevated(P＜0.01).Com-pared to the model group,the donepezil hydrochloride and TST groups effectively improved the aforementioned indicators.CONCLUSION:Total saponins of trillium tschonoskii maxim can effectively alleviate pathological damage to neurons in VD rats,thereby improving learning and memory abilities.The underlying mechanisms may involve inhibiting the overacti-vation of astrocytes,activate the Shh/Ptch1/Gli1 signaling pathway,suppress neuroinflammation,and reduce neuronal apoptosis.

Objective:To explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

AIM:To observe the neuroprotective effects of total saponins of Trillium tschonoskii Maxim(TST)on rats with vascular dementia(VD)and explore the drug's impact on astrocytes and the Sonic Hedgehog(Shh)pathway as well as its mechanisms of action.METHODS:A rat model of vascular dementia was established by bilateral common carotid artery occlusion.Subsequently,the rats were randomly divided into four groups:donepezil hydrochloride group,TST group,model group,and sham group,with 18 rats in each group.After 5 weeks of gavage,samples were collected.Cognitive function was evaluated by the water maze test.Histopathological changes in brain tissue were examined with HE and Nissl staining.The ultrastructure of astrocytes was analyzed by transmission electron microscopy.The localization and expression of the neuronal nuclear antigen(NeuN),glial fibrillary acidic protein(GFAP),Shh,and glioma-associated oncogene homolog 1(Gli1)were identified using immunohistochemistry.Immunofluorescence was also employed to exam-ine the expression of NeuN and GFAP.Finally,Western blot analysis was used to measure the protein levels of NeuN,GFAP,Shh,Patched 1(Ptch1),Gli1,Bax,Bcl-2,tumor necrosis factor-α(TNF-α),and interleukin-10(IL-10)in the hippocampus.RESULTS:Compared to the sham group,the model rats demonstrated prolonged escape latency,disorga-nized and loosened neuronal arrangement in the hippocampus and cortex,reduced Nissl bodies,and significant neuronal damage.Astrocytes displayed chromatin aggregation,swollen mitochondria with disrupted cristae structures,and swollen endoplasmic reticulum regions.The expression of NeuN,Shh,and Gli1 positive cells significantly decreased,while GFAP positive cells significantly increased.Additionally,the protein levels of NeuN,Shh,Ptch1,Gli1,IL-10,and Bcl-2 in the hippocampus were reduced(P＜0.05),whereas those of GFAP,Bax,and TNF-α were elevated(P＜0.01).Com-pared to the model group,the donepezil hydrochloride and TST groups effectively improved the aforementioned indicators.CONCLUSION:Total saponins of trillium tschonoskii maxim can effectively alleviate pathological damage to neurons in VD rats,thereby improving learning and memory abilities.The underlying mechanisms may involve inhibiting the overacti-vation of astrocytes,activate the Shh/Ptch1/Gli1 signaling pathway,suppress neuroinflammation,and reduce neuronal apoptosis.

Objective:To explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

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.

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 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.