ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Ankylosing spondylitis(AS)is a typical spinal arthritis characterised by inflammatory back pain,which seriously affects the health and quality of life of patients.The clinical efficacy of Chinese medicine in the treatment of ankylosing spondylitis is clear,but the mechanism is not clear,and the existing animal models cannot be well applied to the evaluation of Chinese medicine in the treatment of ankylosing spondylitis.Therefore,this paper summarizes the existing animal models based on Chinese and Western medicine clinical diagnosis,disease characteristics,etiology and Chinese medicine evidence,and finds that among the existing animal models,the proteoglycan-induced arthritis mouse model has a higher Chinese and Western medicine clinical fit than the other models,but lacks the corresponding Chinese medicine evidence model evaluation.The other animal models had a higher Western clinical match,but lacked the characteristics of the Traditional Chinee Medicine(TCM)syndrome.As ankylosing spondylitis is a chronic inflammatory autoimmune disease with complex pathogenic factors,the existing animal models cannot better simulate the clinical symptoms.Therefore,the establishment of animal models of ankylosing spondylitis with the characteristics of Chinese and Western clinical evidence is a future research priority for AS TCM.

AIM:To investigate the inhibitory ef-fect of Zushima ointment on inflammation and bone destruction in CIA mice.METHODS:SPF grade male DBA/1 mice were used,6 were random-ly selected as the normal group,and 18 CIA mice that were successfully modelled were randomly di-vided into the model group,the plaster group(1.0 g/kg),and the fuselage group(0.12 g per time)ac-cording to the random number table method,6 mice in each group,and each administered group was given medication according to the body mass,and saline was given to both the normal and model groups.The normal group and the model group were given saline,and breathable adhesive paper was applied once a day for 4 h/session for 4 consec-utive weeks.The arthritis scoring index was used to observe the changes of arthritis symptoms and ar-thritis index scores of mice in each group.Micro-CT was used to observe the damage of hind paw of mice,real-time fluorescence PCR was used to de-tect the mRNA expression of IL-17,IL-1β and TNF-αin ankle joint tissues,and immunohistochemistry was used to detect the expression of OPG and RANKL proteins in ankle joint tissues,and hematox-ylin-eosin(HE)staining was used to observe the pathological changes of synovial tissues after the treatment.The pathological changes of synovial tis-sue were observed after hematoxylin-eosin(HE)staining,and the changes of osteoclasts in ankle joint tissue were observed by anti-tartaric acid phosphatase(TRAP)method.RESULTS:Compared with the normal group,the arthritis index score of the model mice was significantly higher(P＜0.05).Micro-CT showed severe bone erosion in the hind paws of the mice,destruction of the bone surface and reduction of bone volume.The expression of IL-17,IL-1β and TNF-α mRNA(PCR)in the ankle joint tissues was significantly higher(P＜0.05).Im-munohistochemistry showed that the relative ex-pression of OPG protein in the ankle joint tissues was reduced(P＜0.05).Immunohistochemistry showed a decrease in the relative expression of OPG protein(P＜0.01)and an increase in the rela-tive expression of RANKL protein(P＜0.01).HE re-sults showed moderate inflammatory cell infiltra-tion,swelling of synovial cells,massive formation of vascular opacities and synovial hyperplasia;an increase in the number of osteoclasts,roughness of the surface of articular cartilage tissue,severe bone destruction and thinning of the cartilage lay-er.Compared with the model group,the arthritic symptoms of mice in the cream group and the futa-lin group were relieved and the arthritis index score was reduced;the bone density of the mice's hind paws improved,effectively relieving osteopo-rosis;the expression of IL-17,IL-1β and TNF-αmRNA(PCR)in the ankle joint tissue was signifi-cantly reduced(P＜0.05);the immunohistochemical results showed that the relative expression of OPG protein was increased(P＜0.05),the relative expres-sion of RANKL protein decreased(P＜0.01).HE re-sults showed that synovial cell enlargement was significantly improved,mild inflammatory cell infil-tration,synovial hyperplasia was not obvious;the number of broken bone was reduced,articular car-tilage destruction was significantly improved and relieved,and the thickness of cartilage layer was significantly increased.CONCLUSION:Ancestral hemp poultice relieves local symptoms of RA,re-duces the expression of inflammatory factors and attenuates the inflammatory response,possibly by inhibiting osteoclast differentiation and activation through modulation of the OPG/RANKL signalling axis,which further ameliorates the biological ef-fects of articular bone and cartilage destruction.

Rheumatoid arthritis(RA)is an autoimmune disease with the basic pathological manifestation of synovial inflammation.Symmetric poly-articular pain and swelling are the main symptoms in clinical practice,and even extra-articular manifestations and comorbidities such as interstitial fibrosis and coronary artery disease are triggered,which seriously affect the quality of life of patients.Traditional Chinese medicine(TCM)has achieved good clinical efficacy in the prevention and treatment of RA with the advantages of multi-pathway,multi-target,multi-component,and less toxic side effects,and plays an important role in the treatment of RA.Recently,many studies have demonstrated that Chinese medicine monomers and Chinese herbal compound can control inflammation,reduce angiogenesis,induce apoptosis of synovial fibroblasts,and inhibit their proliferation,invasion and migration by regulating the PI3K/Akt signaling pathway,so as to play a key role in the treatment of RA.For this reason,the article summarizes current knowledge regarding the PI3K/Akt signaling pathway and its role in RA,as well as summarizes the current research progress of TCM in the treatment of RA by regulating the PI3K/Akt signaling pathway.The aim of this review is to provide theoretical bases for the prevention and treatment of RA and the development of new drugs.

Ankylosing spondylitis(AS)is a chronic inflammatory autoimmune disease characterized by inflammatory back pain.Its pathological features mainly include inflammation,bone destruction,and pathologic new bone formation.The etiology of AS is complex,and it may be related to genetics,infections,the environment,and intestinal flora.Its pathogenesis has not yet been clarified.In recent years,osteoimmunology,as a new theme in the study of inflammatory arthritis,plays an important role in the pathogenesis and development of AS,which was embodied in the inflammatory response and imbalance of bone metabolism.Traditional Chinese medicine(TCM)has the characteristics of multiple pathways,multiple components,multiple targets and multiple levels.TCM can improve the inflammatory response and bone metabolism imbalance of AS by regulating the osteoblasts of the skeletal system and the related factors of the immune system,thus to prevent and control AS.For this reason,the paper summarizes the role of bone immunology in the pathogenesis of AS,and reviews the current status of research on the intervention of TCM in bone immunology for the treatment of AS,with a view to providing certain references for the future clinical application of TCM in the prevention and treatment of AS.

Osteoporosis (OP) is a prevalent metabolic bone disease with a complex pathogenesis that has not yet been fully elucidated. Recent studies have revealed that the Toll-like receptor 4 (TLR4) signaling pathway plays a significant role in the development and progression of OP. TLR4, a crucial immune receptor primarily expressed in immune cells, is involved in inflammatory responses and immune regulation. The TLR4 signaling pathway influences bone metabolism and remodeling through multiple mechanisms. Therefore, investigating the role of the TLR4 signaling pathway in OP is of great significance for its prevention and treatment. Research targeting the TLR4 signaling pathway provides novel insights and approaches for OP therapy. Future studies should further explore the mechanisms of the TLR4 signaling pathway, develop therapeutic agents that modulate this pathway, and validate their efficacy in OP through clinical trials, thereby offering more options for the clinical management of OP.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that affects multiple systems and organs throughout the body. Thrombotic microangiopathy (TMA) is a rare clinical syndrome that can lead to multiple organ dysfunction and even threaten life. Clinically, SLE patients with TMA are relatively rare, especially in children, but the mortality of SLE patients with TMA is significantly increased. The article reports 2 cases of successful remission of SLE complicated with TMA after treatment with eculizumab, and discusses the diagnosis, clinical manifestations and treatment of SLE complicated with TMA in children, so as to provide clinical basis for the diagnosis and treatment of SLE complicated with TMA in children.

Objective To investigate the effect of intestinal mucosal Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathway on renal damage in pseudo-sterile IgA nephropathy (IgAN) mice. Methods C57BL/6 mice were randomly divided into experimental group (pseudosterile mouse model group), control group (IgAN mouse model group), pseudosterile mouse blank group, and normal mouse blank group. Pseudosterile mice were established by intragastric administration of quadruple antibiotics once a day for 14 days. The pseudosterile IgAN mouse model was set up by combination of oral bovine serum albumin (BSA) administration and staphylococcal enterotoxin B (SEB) injection. The pathological changes of renal tissue were observed by immunofluorescence staining and PAS staining, and the intestinal mucosa barrier damage indicators lipopolysaccharide(LPS), soluble intercellular adhesion molecule 1(sICAM-1) and D-lactate(D-LAC) were analyzed by ELISA. Biochemical analysis was used to test 24 hour urine protein, serum creatinine and blood urea nitrogen. The mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB (NF-κB) were detected by reverse transcription PCR and Western blot analysis. Results The kidney damage of pseudosterile IgAN mice was more severe than that of IgAN mice, and the expressions of intestinal mucosal barrier damage markers (LPS, sICAM-1 and D-LAC) were significantly increased in pseudosterile IgAN mice. In addition, the expressions of TLR4, MyD88, and NF-κB level were all up-regulated in the intestinal tissues of IgAN pseudosterile mice. Conclusion Intestinal flora disturbance leads to intestinal mucosal barrier damage and induces activation of TLR4 signaling pathway to mediate renal injury in IgAN.
Animals ; Mice ; Mice, Inbred C57BL ; Glomerulonephritis, IGA ; NF-kappa B ; Toll-Like Receptor 4/genetics* ; Lipopolysaccharides ; Myeloid Differentiation Factor 88/genetics* ; Kidney ; Intestinal Mucosa ; Infertility ; Disease Models, Animal

Objective : To study the mechanism of neurotrophin receptor⁃interacting MAGE homolog (NRAGE) on the proliferation and invasion of colorectal cancer (CRC) cells. Methods : The clinicopathological data of 84 CRC patients were selected. Fluorescence quantitative PCR (qPCR) and Western blot were used to detect the expression of NRAGE in CRC tissues and adjacent normal tissues. The relationship between the expression of NRAGE in cancer tissues and clinicopathological characteristics was analyzed statistically. RT⁃PCR and Western blot were used to detect the expression of NRAGE mRNA and protein in CRC tumor cell lines HT29 , SW480 , SW620 , LOVO and colorectal normal cell line FHC. MTT proliferation experiment and Transwell migration experiment were used to observe the tumor cell proliferation and migration ability of the NC group , overexpression NRAGE group and NRAGE knockdown group. The expression differences of AKT , p ⁃AKT , ERK1/2 , p ⁃ERK1/2 , E ⁃cadherin , N ⁃cadherin and Vimentin were detected by qPCR and Western blot. Results : Compared with adjacent tissues , NRAGE mRNA and protein expression in CRC cancer tissues were significantly higher. The expression of NRAGE in cancer tissues was related to tumor stage , distant metastasis and lymph node metastasis (all P < 0. 05) . Compared with FHC cells , CRC tumor cell lines HT29 , SW480 , SW620 , and LOVO cells had higher NRAGE mRNA and protein expression (P < 0. 05) . Compared with the NC group , the proliferation and migration ability of CRC tumor cells in the overexpression NRAGE group was significantly enhanced , while the knockdown group was significantly weakened. Compared with the NC group , the SW480 cells in the overexpression NRAGE group had higher p ⁃ERK1/2 protein expression , but there was no significant difference in the expression of ERK1/2 , AKT and p ⁃AKT. After the SW480 cells in the overexpression NRAGE group were treated with ERK inhibitor U0126 , the proliferation and migration ability of SW480 cells significantly reduced. Methods NRAGE can promote the epithelial⁃mesenchymal transition of CRC cells and enhance the proliferation and migration of CRC tumor cells by activating ERK signaling pathway.

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.