OBJECTIVE Aimed to comprehensively evaluate various immunological changes in a mouse model of eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP)induced by ovalbumin(OVA)combined with Aspergillus protease(AP),including nasal polyps-like lesions,subepithelial collagen deposition,inflammatory cell infiltration,epithelial barrier function,and olfactory neuron damage.METHODS C57BL/6 mice were challenged with OVA and AP for 12 weeks.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe the changes of nasal polyps-like lesions,goblet cell hyperplasia,and subepithelial collagen deposition.Immunohistochemistry staining(IHC)was employed to detect the changes of various inflammatory cells,olfactory neurons,and the expression of epithelial tight junction proteins in the nasal and sinus mucosa.RESULTS Compared to the control group,the OVA and AP group showed significantly increased epithelial thickness,noticeable nasal polyps-like lesions,marked subepithelial collagen deposition,and goblet cell hyperplasia in the nasal and sinus mucosa.IHC results revealed a significant increase in eosinophils,along with higher numbers of neutrophils,mast cells,and CD4+T cells in the OVA and AP group.Additionally,the expression of tight junction proteins ZO-1 and E-cadherin in the nasal and sinus mucosa and the area of OMP+olfactory neurons in the olfactory epithelium were significantly lower in the OVA and AP group compared to the control.CONCLUSION Continuous exposure to OVA combined with AP successfully induces ECRSwNP.The establishment of this model provides a foundation for further research into the pathogenesis and the evaluation of new therapeutic strategies for ECRSwNP.

OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system， optimization measures were taken， including improving the content of the rule base， adjusting the interception level and prompt mode， refining the working model of prescription review pharmacists， and strengthening clinical communication. A retrospective cohort study was conducted， with prescription data from June to December 2023 （before optimization） as the control group and June to December 2024 （after optimization） as the observation group. Through inter group comparative analysis， the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from （82.51± 4.04）% before optimization to （90.98±1.55）% after optimization； the false positive rate decreased from （20.87±1.64）% before optimization to （7.41±2.04）% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%， and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%， the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital， its prescription review efficiency has been significantly enhanced， the quality of prescriptions has steadily improved， and the accuracy of reviews has notably improved.

Three-dimensional printed patient-specific instrumentation (3D-PSI) provides a precise and individualized treatment solution for unicompartmental knee arthroplasty (UKA). Currently, this technology is being applied in clinical practice and has demonstrated certain potential. Compared to conventional instrumentation (CI), 3D-PSI offers a broader range of indications, higher-quality preoperative planning, shorter surgical time, a smoother learning curve, more precise osteotomy and prosthesis placement, and better postoperative functional recovery. However, it still has limitations in the rotational alignment of the tibial component. Additionally, the higher cost for patients and increased hospital equipment investment make it less beneficial for surgeons already proficient in CI techniques. Further reliable evidence is needed to compare 3D-PSI with computer navigation and robotic technologies. This review summarizes the advantages and limitations of 3D-PSI assisted UKA and compares 3D-PSI with different auxiliary technologies.

BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.

BACKGROUND:Interleukin-4 can promote the osteogenic effect of bone substitute materials,but its molecular mechanism is not yet clear.Further elucidating the mechanism of interleukin-4 promoting osteogenic effect can help find safe,economical,and effective methods for the regeneration treatment of alveolar bone defects in patients. OBJECTIVE:To explore the effect of interleukin-4 intervention on polarization transformation of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells and its possible mechanism. METHODS:RAW264.7 cells in the M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours.RAW264.7 cells in the interleukin-4+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours and then interleukin-4 was added for 24 hours.RAW264.7 cells in the interleukin-4+AG+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours,and then interleukin-4 and AG-490,a JAK/STAT pathway inhibitor,were added for 24 hours.After intervention,immunofluorescence staining was used to analyze the expression of inducible nitric oxide synthase and CD206,the phenotypic marker protein of macrophages.ELISA kit was used to detect the expression of interleukin-10 and tumor necrosis factor-α in the supernatant of cell culture.The gene expressions of nodular receptor protein-3(NLRP3),interleukin-1β,and caspase-1 were detected by RT-qPCR.The expression levels of tyrosine protein kinase 1(JAK1)/phosphorylated tyrosine protein kinase 1(p-JAK1),signal transduction and transcription activator 6(STAT6)/phosphorylated signal transduction and transcription activator 6(p-STAT6),NLRP3,pro-interleukin-1β and pro-caspase-1 were detected by western blot assay.Then,RAW264.7 cells in the above four groups were indirectly co-cultured with bone marrow mesenchymal stem cells by transwell for 24 hours,followed by alkaline phosphatase staining and alizarin red staining.The mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were detected by RT-qPCR. RESULTS AND CONCLUSION:(1)Immunofluorescence and ELISA results showed that interleukin-4 intervention could promote the expression of CD206 and interleukin-10 in M2 macrophages,and inhibit the secretion of inducible nitric oxide synthase and tumor necrosis factor-α.(2)RT-qPCR results showed that interleukin-4 could suppress the expression of NLRP3,interleukin-1β,and caspase-1 mRNAs.(3)Western blot assay showed that interleukin-4 could promote the expression of JAK1/p-JAK1,STAT6/p-STAT6 and NLRP3 proteins.(4)The alkaline phosphatase staining and alizarin red staining of bone marrow mesenchymal stem cells co-cultured with the interleukin-4+M1 group were significantly enhanced,and the mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were significantly increased.It is concluded that interleukin-4 may inhibit the activation of NLRP3 by up-regulating JAK1/STAT6 pathway,thus promoting the transformation of macrophages from M1 polarization to M2 polarization,and finally enhancing the osteogenic differentiation ability of bone marrow mesenchymal stem cells.

Objective To prepare injectable poly(lactic-co-glycolic)acid(PLGA)microparticle scaffolds coated with a composite of polydopamine(PDA)and carboxymethyl chitosan(CMC),and to evaluate their biocompatibility and capacity for cell loading in tissue engineering.Methods The injectable PLGA microparticles were prepared using the W/O/W double-emulsion solvent evaporation method,followed by PDA and CMC coatings to prepare the porous scaffolds that were morphologically characterized while the size distribution of particles and pores was determined.Cytotoxicity was assessed via co-incubation of the scaffolds with cells,while cell viability was evaluated using the CCK-8 assay.The morphology of cells loaded onto the scaffolds was examined using scanning electron microscopy and DAPI staining.Results The average particle size of the prepared PLGA-PDA-CMC porous scaffolds was(313.69±4.91)μm,and the average pore size was(28.99±0.74)μm.Scanning electron microscopy confirmed the success of the PDA coating while X-ray photoelectron spectroscopy proved the success of the PDA and CMC coatings.The reduced water contact angle post-PDA coating indicated enhanced hydrophilicity of the PLGA microparticles.CCK-8 assay results demonstrated the safety of the PLGA-PDA-CMC porous scaffolds.Scanning electron microscopy and fluorescence microscopy confirmed cell adhesion on the PLGA-PDA-CMC porous scaffolds.Conclusion The successful preparation of PLGA-PDA-CMC porous scaffolds,featuring PDA and CMC coatings,can enhance the hydrophilicity and cell adhesion properties of PLGA microparticles.These scaffolds can be potentially used in tissue engineering research.

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

As a glucocorticoid drug with wide clinical application， triamcinolone acetonide can be administered by multiple routes， such as eye， nose， joint cavity， and skin， for the treatment of various local diseases such as arthritis， macular edema， rhinitis， and urticaria. As a drug with extremely low solubility in water， the dose form of triamcinolone acetonide is closely correlated with administration route and site. The dosage form of triamcinolone acetonide administered via injection（including joint cavity injection， vitreous injection， suprachoroidal injection， intramuscular injection） is mainly suspension， and the representative drugs include Kenalog-40®， Zilretta®， Triesence®， Xipere®， etc.； the dosage forms of nasal mucosal administration are mostly sprays， and the representative drug is Nasacort®； the dosage forms of oral mucosal administration are mostly patches， ointments and creams， and the representative drug is Oracort®； the dosage forms for transdermal administration are mostly ointments， creams and lotions， and the representative drugs include Trianex®， Teva-Triacomb®， etc. At present， the research on dosage forms of triamcinolone acetonide by various administration routes mainly focuses on the construction of delivery carriers， the addition of cosolvents or the use of new delivery tools.

Middle-aged and elderly patients with femoral neck fracture often suffer from basic diseases. Conservative treatment will significantly increase the incidence of complications. At present, surgical treatment is mostly advocated. Internal fixation is one of the effective treatment methods for middle-aged and elderly patients with femoral neck fracture. It has the advantages of improving hip joint function, accelerating patient recovery, and improving patient quality of life. At present, there are many choices of internal fixation in the world, each has its own advantages and disadvantages, and there is no unified standard. Different surgical methods can be selected according to various factors such as fracture type, patient′s physical condition and surgical auxiliary technology. This article reviews the clinical progress of internal fixation for femoral neck fractures in middle-aged and elderly patients from four aspects: the characteristics of femoral neck fractures in middle-aged and elderly patients, common internal fixation methods, 3D printing guide plate auxiliary technology and artificial intelligence auxiliary technology.