ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

Objective:To explore the effect and safety of CO 2 fractional laser combined with botulinum toxin type-A (BTX-A) in the treatment of keloid. Methods:A total of sixty patients with keloids admitted to the First Affiliated Hospital of Zhengzhou University from December 2021 to September 2023 were prospectively included. The patients were divided into two groups using the random number table method: observation group (30 cases), including 12 males and 18 females, with an average age of (18.3±6.9) years, were treated with CO 2 fractional laser combined with Botox type A; control group (30 cases), including 13 males and 17 females, with an average age of (21.0±7.7) years, were treated with CO 2 fractional laser alone. The two groups received treatment once a month for 6 months. The total effective rate of the two groups after treatment were compared. The Vancouver scar scale (VSS) was used to evaluate the morphology of scars (including color, thickness, vascular distribution, and hardness) before and after treatment. Visual analog scale (VAS) was used to assess the degree of pain before and after treatment. The patient self-assessment (PSA) was used to evaluate the degree of itching before and after treatment. The incidence and recurrence of adverse reactions such as tissue depression, capillary dilation, skin atrophy, pigmentation and depigmentation were statistically compared between the two groups after treatment. Results:The total effective rate of the observation group was 93.3% (28/30), which was higher than that of the control group [73.3% (22/30), P=0.012]. After treatment, the scores of VSS, VAS and PSA in the observation group were lower than those in the control group (all P<0.05). The recurrence rate and adverse reaction rate of the observation group were 6.7% (2/30) and 6.7% (2/30), respectively, which were lower than that of the control group [43.3% (13/30) and 40.0% (12/30)], and the difference was statistically significant (all P<0.05). The adverse reactions in the observation group included tissue depression in 1 case and pigment loss in 1 case, while those in the control group included capillary dilation in 1 case, skin atrophy in 5 cases, pigmentation in 4 cases and pigment loss in 2 cases. Conclusion:The combination of CO 2 dot laser and BTX-A injection has a good effect on keloid and a low incidence of adverse reactions.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

Objective:To explore the effect and safety of CO 2 fractional laser combined with botulinum toxin type-A (BTX-A) in the treatment of keloid. Methods:A total of sixty patients with keloids admitted to the First Affiliated Hospital of Zhengzhou University from December 2021 to September 2023 were prospectively included. The patients were divided into two groups using the random number table method: observation group (30 cases), including 12 males and 18 females, with an average age of (18.3±6.9) years, were treated with CO 2 fractional laser combined with Botox type A; control group (30 cases), including 13 males and 17 females, with an average age of (21.0±7.7) years, were treated with CO 2 fractional laser alone. The two groups received treatment once a month for 6 months. The total effective rate of the two groups after treatment were compared. The Vancouver scar scale (VSS) was used to evaluate the morphology of scars (including color, thickness, vascular distribution, and hardness) before and after treatment. Visual analog scale (VAS) was used to assess the degree of pain before and after treatment. The patient self-assessment (PSA) was used to evaluate the degree of itching before and after treatment. The incidence and recurrence of adverse reactions such as tissue depression, capillary dilation, skin atrophy, pigmentation and depigmentation were statistically compared between the two groups after treatment. Results:The total effective rate of the observation group was 93.3% (28/30), which was higher than that of the control group [73.3% (22/30), P=0.012]. After treatment, the scores of VSS, VAS and PSA in the observation group were lower than those in the control group (all P<0.05). The recurrence rate and adverse reaction rate of the observation group were 6.7% (2/30) and 6.7% (2/30), respectively, which were lower than that of the control group [43.3% (13/30) and 40.0% (12/30)], and the difference was statistically significant (all P<0.05). The adverse reactions in the observation group included tissue depression in 1 case and pigment loss in 1 case, while those in the control group included capillary dilation in 1 case, skin atrophy in 5 cases, pigmentation in 4 cases and pigment loss in 2 cases. Conclusion:The combination of CO 2 dot laser and BTX-A injection has a good effect on keloid and a low incidence of adverse reactions.

Ankylosing spondylitis （AS） is an inflammatory autoimmune disease with chronic low back pain as the main clinical manifestation， which mainly affects the axial joints， peripheral joints and various organs. In severe cases， the spine is stiff or deformed， which affects the quality of life and health of patients. The pathogenic factors of AS are complex， which are related to heredity， immunity and intestinal flora. The pathogenesis of AS is not clear yet. Among them， inflammatory reaction， bone destruction and heterotopic ossification are the main pathological features of AS， which play an important role in the disease process of AS. Traditional Chinese medicine has multi-target， multi-channel and multi-component pharmacological effects， which can prevent and treat AS by anti-inflammation， inhibiting bone destruction and preventing heterotopic ossification， and the clinical effect is remarkable， but there is no relevant literature report. Therefore， this review expounds the relationship between inflammatory reaction， bone destruction and heterotopic ossification and the occurrence and development of AS， and summarizes the latest research reports of traditional Chinese medicine in treating AS from anti-inflammatory， inhibiting bone destruction and preventing heterotopic ossification， aiming at providing reference and new ideas and directions for further research on the prevention and treatment of AS by traditional Chinese medicine.

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.

Objective:To explore the effect of the medical alliance co-management hierarchical diagnosis and treatment model in the hospital-community comprehensive management of diabetic foot patients.Methods:From June to December 2020, convenience sampling was used to select 134 diabetic foot patients in the Endocrinology Department of the First Affiliated Hospital of Zhengzhou University as the research subject. According to the random number table method, the patients were divided into the control group and the observation group, 67 cases in each. The control group conducted routine management, while the observation group carried out hospital-community comprehensive management based on the medical alliance co-management hierarchical diagnosis and treatment model. Patients were surveyed using the Diabetic Foot Self-Care Questionnaire of the University of Malaga (DFSQ-UMA) . The Wagner grade and progression of diabetic foot, the risk factors of diabetic foot and the foot self-care were compared between the two groups.Results:After intervention, there were more patients with Wagner grade 0, 1 and 2 in the observation group than the control group, and fewer patients with Wagner grade 3, 4 and 5 than the control group. The number of diabetic foot progression cases in the observation group and the control group were 6 cases (8.96%) and 19 cases (28.36%) , respectively, and the difference was statistically significant (χ 2=8.310, P=0.004) . After intervention, the score of the Scale of High Risk Factors of Diabetic Foot of the observation group was lower than that of the control group, and was lower than the score before intervention, and the differences were statistically significant ( P<0.05) . After intervention, the DFSQ-UMA dimension scores in the observation group were higher than those in the control group, and were higher than those before intervention, and the differences were statistically significant ( P<0.05) . Conclusions:The hospital-community comprehensive management based on the medical alliance co-management hierarchical diagnosis and treatment model can effectively delay the progression of patients with diabetic foot, reduce the risk factors of diabetic foot, and improve the patients' foot self-care.