The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerular disease (C3G) and age-related macular degeneration (AMD). Complement factor B (CFB) is a trypsin-like serine protein that circulates in the human bloodstream in a latent form. As a key node of the alternative pathway, it is an important target for the treatment of diseases mediated by the complement system. With the successful launch of iptacopan, the CFB small molecule inhibitors has become a current research hotspot, a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors. In this paper, the research progress of CFB small molecule inhibitors in recent years is systematically summarized, the representative compounds and their activities are introduced according to structural types and design ideas, so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology, primarily characterized by systemic inflammation and hyperactivation of both B and T lymphocytes. Key immunological features include increased consumption of complement components, sustained overproduction of type I interferons (IFN-I), and persistent production of a broad spectrum of autoantibodies, such as anti-dsDNA antibodies. However, the use of autoantibodies as biomarkers for the early detection of SLE is associated with a high false-positive rate, suggesting that antibody characteristics evolve during disease progression.N-glycosylation is a critical post-translational modification of antibodies that significantly influences their structure and receptor-binding properties, thereby modulating biological activities and functions. In particular, glycosylation patterns affect the antibody’s affinity for Fc gamma receptors (FcγRs), subsequently regulating various antibody-mediated immune responses. Numerous studies have investigated the impact of individual monosaccharides—such as sialic acid, fucose, and N-acetylglucosamine, which constitute N-glycans—on the immunological functions of antibodies. This review systematically summarizes the aberrant immunoglobulin G (IgG) N-glycosylation patterns observed in SLE patients, with a focus on correlations between disease progression or complications and quantitative alterations in individual glycan components. We first review how different types of N-glycosylation modifications affect the biological activity and functional properties of IgG, particularly regarding the effects of specific monosaccharides—such as sialic acid, fucose, and galactose—on FcγR binding affinity and the resulting downstream immune functions. We then summarize the differential expression of IgGN-glycans and glycosyltransferase genes between SLE patients and healthy controls, and outline the associations between glycosylation changes and SLE-related pathological responses. In response to the inconsistencies and limitations in current research, we propose potential explanations from the perspectives of study methodologies, participant characteristics, and variations in N-glycan structures, aiming to provide a constructive reference for future studies. Given the close relationship between antibody glycosylation and SLE, this review highlights the potential of IgG N-glycosylation patterns as promising biomarkers for early diagnosis and disease monitoring. In terms of therapy, we discuss how IgG glycosylation can enhance the efficacy of intravenous immunoglobulin (IVIg) treatment and introduce emerging therapeutic strategies that aim to modulate endogenous IgG N-glycans as a novel glycan-based approach for SLE management. In summary, N-glycans are essential structural components of antibodies that regulate immune responses by modulating antibody-receptor interactions. Aberrant glycosylation is closely associated with the pathogenesis of autoimmune diseases, including SLE. However, due to the structural diversity of N-glycans and the complexity of glycosylation processes, the precise roles of IgGN-glycosylation in SLE pathophysiology remain incompletely understood. Moreover, therapeutic strategies targeting IgG glycosylation are still in early development and have not yet reached clinical application. Continued progress in glycan analysis technologies and other biological tools, along with interdisciplinary collaboration, will be essential for advancing this field.

OBJECTIVE To study the effects of sophoranone （SOP） on the biological behavior of nasopharyngeal carcinoma CNE-1 cells and mitogen-activated protein kinase （MAPK） signaling pathway. METHODS CNE-1 cells were divided into blank group and SOP low-， medium- and high-concentration groups （SOP-L group， SOP-M group， SOP-H group， 25， 50 and 100 μmol/L）. The number of invasive cells， the number of migratory cells， and the apoptosis rate of cells were detected. The expression levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase 1 （ERK1）， ERK2， and c-Jun N-terminal kinase （JNK） mRNA， as well as phosphorylation levels of ERK， JNK， and p38 mitogen-activated protein kinase （abbreviated as “p38”） proteins in cells were all detected. Additionally， cells were divided into blank group， SOP high-concentration group （SOP- H group， 100 μmol/L）， SOP high-concentration combined with p38 inhibitor group （SOP-H+SB group， 100 μmol/L SOP+10 μmol/L SB）， and SOP high-concentration combined with JNK inhibitor group （SOP-H+SP group， 100 μmol/L SOP+10 μmol/L SP）. The number of invasive cells， cell migration rate， and the protein phosphorylation levels of JNK and p38 in cells， as well as the protein expression levels of matrix metalloproteinase-9（MMP-9）， proliferating cell nuclear antigen Ki67， and cleaved-caspase-3 were measured. RESULTS Compared with the blank group， SOP for each concentration could significantly decrease the number of invasive cells， the number of migratory cells， and mRNA expressions of MEK， ERK1， ERK2 （except for the SOP-L group） and JNK， but increase the apoptosis rate of cells and phosphorylation levels of ERK， JNK， and p38 proteins （P＜0.05）. Compared with the SOP-H group， the protein phosphorylation levels of p38 and JNK， and the protein expression of cleaved-caspase-3 were decreased significantly in SOP-H+SB group and SOP-H+SP group， while the number of invasive cells， cell migration rate， and the protein expression levels of MMP-9 and Ki67 were all increased significantly （P＜0.05）. CONCLUSIONS SOP can inhibit the proliferation， migration and invasion of CNE-1 cells， and induce the apoptosis， the mechanisms of which may be associated with promoting the phosphorylation of proteins related to the MAPK signaling pathway.

Objective To investigate the role of microRNA(miR)-567 in the proliferation,migration and cell cycle of non-small cell lung cancer(NSCLC)through regulation of cyclin dependent kinase 8(CDK8)and its clinical relevance.Methods Tumor tissues and adjacent tissues of 40 NSCLC patients were collected,and the expressions of miR-567 and CDK8 were detected by real-time quantitative fluorescent PCR(qRT-PCR).miR-NC mimic,miR-567 mimic,oe-NC,and oe-CDK8 were transfected into A549 and H1975 cells.The ex-pressions of miR-567 and CDK8 were detected using qRT-PCR.Cell proliferation was detected by CCK-8 method,and cell migration was detected by Transwell assay.Cell cycle changes were detected by flow cytome-try.The targeting of miR-567 and CDK8 was detected by luciferase reporter gene assay.Results In the tumor tissues of NSCLC patients,the expression of miR-567 was decreased,while the expression of CDK8 was in-creased,and the two were negatively correlated(P＜0.05).In A549 and H1975 cells,miR-567 mimic group was compared with miR-NC mimic group,the expression of miR-567 was increased,the expression of CDK8 was decreased,the proliferation and migration levels of cells were decreased,the proportion of G1 phase was increased,and the proportion of S phase was decreased.The fluorescence intensity of miR-567 mimic group was lower than that of miR-NC mimic group in normal CDK8.miR-567 mimic+oe-CDK8 group was compared with miR-567 mimic+oe-NC group,the expression of CDK8 was increased,the proliferation and migration levels of cells were increased,the proportion of cells in G1 phase was decreased,and the proportion of cells in S phase was increased.Conclusion miR-567 can inhibit NSCLC proliferation and migration by targeting CDK8 expression and controlling tumor cell arrest in the S phase.

Objective:With the in-depth study of complement dysregulation,glomerulonephritis with dominant C3 has received increasing attention,with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types.This study analyzes the clinical,pathological,and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3,aiming to avoid misdiagnosis and missed diagnoses. Methods:The clinical,pathological,and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed.According to the clinical feature and results of pathology,15 patients with post-infectious glomerulonephritis(PIGN)and 37 patients with of non-infectious glomerulonephritis(N-PIGN)were classified.N-PIGN subgroup analysis was performed,and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group,or 27 in a C3 glomerulopathy(C3G)group and 10 in a non-C3 nephropathy(N-C3G)group. Results:The PIGN group had lower creatinine values(84.60 μmol/L vs 179.62 μmol/L,P= 0.001),lower complement C3 values(0.36 g/L vs 0.74 g/L,P<0.001)at biopsy,and less severe pathological chronic lesions compared with the N-PIGN group.In the N-PIGN subgroup analysis,the C3-dominant-deposition group had higher creatinine values(235.30 μmol/L vs 106.70 μmol/L,P=0.004)and higher 24-hour urine protein values(4 025.62 mg vs 1 981.11 mg,P=0.037)than the C3-alone-deposition group.The prognosis of kidney in the PIGN group(P=0.049),the C3-alone-deposition group(P=0.017),and the C3G group(P=0.018)was better than that in the N-PIGN group,the C3-dominant-deposition group,and the N-C3G group,respectively. Conclusion:Glomerulonephritis with dominant C3 covers a variety of pathological types,and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G;in addition,the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis,and relevant diagnosis,treatment,and follow-up should be strengthened.

BACKGROUND:Upregulation of hedgehog protein signaling can increase the expression of osteoarthritis markers,Runx2,a disintegrin and metalloproteinase with thrombospondin motifs,collagen type X alpha 1,and matrix metalloproteinase 13,while inhibition of hedgehog proteins attenuates the severity of osteoarthritis.It is speculated that osteoarthritic chondrocytes can influence bone formation by affecting osteoblasts through the Indian hedgehog protein(IHH)signaling pathway. OBJECTIVE:To investigate the effect of human osteoarthritic chondrocytes on subchondral osteoblasts. METHODS:Tibial plateau specimens from patients with osteoarthritis were collected.Chondrocytes were extracted using enzymatic digestion,and osteoblasts were extracted using enzymatic pre-digestion + bone block method.Chondrocytes were identified by toluidine blue staining and immunofluorescence and osteoblasts were identified by alkaline phosphatase staining and immunofluorescence.Chondrocytes were cultured in sodium alginate beads to maintain chondrocyte phenotype and co-cultured with osteoblasts.The co-culture system was added with IHH signaling pathway inhibitor(cyclopamine,10 nmol/L)and activator(purmorphamine,10 nmol/L)separately.After 48 hours of co-culture,osteoblasts from each group were collected,mRNA expressions of Gli1,osteoprotegerin,Runx2,parathyroid hormone-related peptide,alkaline phosphatase,receptor activator of nuclear factor-kB ligand(RANKL)and osteocalcin were detected by qRT-PCR,and protein expressions of GLi1,oseoprotegerin and RANKL in osteoblasts were detected by western blot. RESULTS AND CONCLUSION:The mRNA expression levels of GLi1,osteoprotegerin and RUNX2 in osteoblasts were significantly increased,while the mRNA expression levels of parathyroid hormone-related peptide were decreased(P＜0.05)when co-cultured with human osteoarthritic chondrocytes.The mRNA and protein levels of Gli1 were significantly decreased after the addition of IHH signaling pathway inhibitor(cyclopamine)(P＜0.05),and the mRNA and protein levels of Gli1 were significantly increased after the addition of IHH signaling pathway activator(purmorphamine)(P＜0.05).Osteoprotegerin showed the same trend as Gli1 in the experiment.The osteoprotegerin/RANKL ratio followed the same trend as osteoprotegerin.To conclude,human osteoarthritic chondrocytes can promote the expression of Gli1,osteoprotegerin,Runx2 and other proteins in osteoblasts.The upregulation of osteoprotegerin is related to the IHH signaling pathway.Osteoarthritic chondrocytes can up-regulate the expression of osteoprotegerin in osteoblasts through the IHH signaling pathway and thus up-regulate the osteoprotegerin/RANKL ratio,which will contribute to bone formation in subchondral bone.

Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.

Objective To evalucate in vitro activity of cefcapene against clinical isolated pathogenic bacteria in recent three years in China.Methods The clinical isolates were collected and the minimal inhibitory concentrations(MICs)were determined by the microbroth dilution method.Results A total of 308 pathogenic bacteria over the period 2021-2023 were studied.Cefcapene exhibited excellent antibacterial activity against Streptococci and methicillin susceptible Staphylococcus aureus(MSSA),which was similar to penicillin and cefpodoxime,and better than cefuroxime,cefaclor and cefixime.Against gram-negative bacteria,cefcapene also showed better antibacterial activity,especially against non-extended spectrum β-lactamases(ESBLs)Escherichia coli,Haemophilus influenzae and Moraxella catarrhalis,were comparable to cefixime and cefpodoxime,better than cefuroxime and cefaclor.Conclusion Cefcapene showed excellent antibacterial activity against clinical isolates from community-acquired pneumonia,include streptococcus pneumonia,MSSA,Haemophilus influenzae and Moraxella catarrhalis in recent years in China,which identical with those reported in literature ten years ago in China and foreign.It is a highly effective oral cephalosporin suitable for adults and children with respiratory tract infection,otitis media,sinusitis,urinary tract infection and other outpatient infections.