ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

Objective: To identify research priorities on physical and mental comorbidity among children and adolescents in Zhejiang Province, so as to provide a theoretical base for improving their physical and mental health. Methods: In May 2025, 77 experts in the fields of health and education from 11 cities in Zhejiang Province were selected by convenient sampling method to participate in the first round of expert consultation. In June, 2025, snowball sampling was used to expand to 194 experts for the second round of consultation, and it was convenient to select 21 students from primary schools to high schools in Zhejiang Province and 29 parents to empower the evaluation criteria. It applied the Child Health and Nutrition Research Initiative (CHNRI) method in a structured process, which encompassed the definition of the research field, generation of research ideas, scoring, and quantitative ranking of priorities. Research ideas were evaluated against 6 predefined criteria: effectiveness, safety, answerability, feasibility, sustainability, and scientific significance. Results: After 2 rounds of structured consultations, 81 research ideas on physical and mental comorbidity among children and adolescents were established and classified into 7 subthemes: epidemiological characteristics and influencing factors, optimization of primary service systems and policies, comprehensive intervention strategies for physical and mental comorbidity, biological mechanisms and clinical research, the impact of education and environment on physical and mental health, special populations and social support, and digital and technology driven disease prevention and intervention. The top 10 research priorities primarily centered on the subdomain of "epidemiological characteristics and influencing factors" (5 items). The top 3 research priorities were "the association between outdoor activity duration and the incidence of common diseases (including mental disorders) among children and adolescents" "the impact of outdoor activity duration on the physical and mental health of adolescents" "comprehensive intervention strategies for myopia, obesity, and their comorbidities among children and adolescents". Conclusion The framework of priority issues in the field of psychosomatic comorbidity of children and adolescents in Zhejiang Province based on CHNRI method provides a reference for optimizing the allocation of provincial research resources.

OBJECTIVE: To compare the aesthetic effects of anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy and whole maxilla clockwise rotation on improving paranasal concavity in patients with Class Ⅲ maxillofacial deformity. METHODS: A non-randomized controlled trial was designed, and 21 patients diagnosed with skeletal Class Ⅲ maxillofacial deformity were included. In the study, 11 patients in the test group were treated by segmental Le Fort Ⅰ osteotomy combined with anterior maxilla clockwise rotation, and 10 patients in the control group were treated by whole maxilla clockwise rotation. The CBCT and 3D photography of preoperative (T0), 2 weeks postoperative (T1), and 6 months postoperative (T2) were collected respectively, and the three-dimensional cephalometry was carried out. The differences of specific parameters between the two groups were compared by independent sample t-test, including saggital displacement of the cheek mass point (CK) and subalare point (SA), nasolabial angle, occlusal plane angle and labial inclination angle of the upper incisor. RESULTS: There were no significant differences of the parameters on T0 between the two groups. The average sagittal displacement of the upper incisors of the test group was (-0.71±1.67) mm and smaller than that of control group [(2.26±1.68) mm], t=-4.052, P < 0.05. The average angle of the occlusal plane clockwise rotation of the test group was 1.46°±2.38° and smaller than that of the control group (4.31°±1.83°), t=-3.047, P < 0.05. The angle of anterior maxilla clockwise rotation was 11.73°±2.81° during the surgery. The average saggital displacement of the paranasal soft tissue landmarks of the test group from T0 to T2 was larger than that of the control group [CK point, (4.96±1.18) mm vs. (2.01± 1.50) mm, P < 0.05;SA point, (5.19±1.17) mm vs. (2.69±1.45) mm, P < 0.05]. The labial inclination angle of the upper incisor of the test group was 112.15°±5.40° in T2 and significantly smaller than that of the control group (122.38°±8.83°), t=-3.237, P < 0.05. The nasolabial angle of the test group was 106.54°±12.82° in T2 and significantly larger than that of the control group (93.90°±12.46°), t=2.288, P < 0.05. CONCLUSION Compared with whole maxilla clockwise rotation, anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy can increase the saggital displacement of the paranasal soft tissue, correct labial inclination of the upper incisors and the acute naso-labial angle and better improve the paranasal aesthetic defects in patients with Class Ⅲ maxillofacial deformity with less changing on the saggital orientation of the upper incisors and the occlusal plane angle.
Humans ; Maxilla/surgery* ; Female ; Male ; Osteotomy, Le Fort/methods* ; Malocclusion, Angle Class III/surgery* ; Adult ; Cephalometry ; Young Adult ; Rotation ; Adolescent

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Objective·To investigate the inhibitory effects of spermidine(SPD)on inflammatory osteolysis both in vivo and in vitro.Methods·The CCK-8 assay was used to assess the viability of RAW264.7 macrophages treated with various concentrations of SPD.The levels of intracellular reactive oxygen species(ROS)in lipopolysaccharide(LPS)-activated RAW264.7 cells were evaluated by staining with dichlorodihydrofluorescein diacetate(DCFH-DA)and dihydroethidium(DHE),respectively.Reverse transcription real-time fluorescence quantitative PCR(RT-qPCR)was utilized to determine the effects of SPD on the expression of pro-inflammatory genes in LPS-activated RAW264.7 cells.Tartrate-resistant acid phosphatase(TRAP)staining was used to evaluate the effect of SPD on the differentiation of mouse primary bone marrow-derived macrophages(BMMs)into osteoclasts.RT-qPCR was employed to further analyze the effect of SPD on the expression of genes related to osteoclast differentiation and functions after BMM-induced differentiation.An LPS-induced mouse calvarial osteolysis model was constructed,and the therapeutic efficacy of SPD on inflammatory osteolysis was assessed using Micro-CT analysis,hematoxylin-eosin(H-E)staining and TRAP staining of histological sections.Results·The CCK-8 assay showed that SPD,even at a concentration of 1 000 μmol/L,exhibited no significant cytotoxicity to RAW264.7 cells.ROS analysis revealed that SPD markedly inhibited LPS-induced elevation of intracellular ROS levels in macrophages.RT-qPCR results indicated that SPD suppressed the expression of pro-inflammatory genes induced by LPS.Both TRAP staining and RT-qPCR demonstrated that SPD effectively inhibited the differentiation of BMMs into osteoclasts induced by receptor activator of nuclear factor-κB ligand(RANKL)and reduced the expression of genes associated with osteoclast differentiation and function.In the mouse calvarial osteolysis model,Micro-CT analysis showed that the bone volume fraction and bone mineral density in the SPD-treated groups were significantly higher than those in the LPS group.Histological staining revealed that SPD treatment reduced inflammatory cell infiltration,decreased osteoclast numbers,and alleviated tissue damage.Conclusion·SPD inhibits macrophage inflammatory responses and RANKL-induced osteoclast differentiation in vitro;in vivo,it alleviates LPS-induced inflammatory calvarial osteolysis in mice.

BACKGROUND:The elastic modulus of traditional solid titanium alloy implants is higher than that of human bone,and the resulting"stress shielding"phenomenon may affect the osseointegration of implants.Simultaneously,the wettability of 3D printed titanium alloy surface needs to be improved.OBJECTIVE:To prepare hydrophilic Gyroid implants with excellent biomechanical properties.METHODS:The 3D models of Gyroid implant,solid implant,mandibular bone and crown were established,and the mechanical properties of different implants were analyzed by finite element analysis.The Gyroid structure implant model was imported into the 3D printer to make the Gyroid structure implant materialized,and then the hydrophilic Gyroid structure implant with excellent mechanical properties and surface activity was prepared by sandblasting acid etching and ultraviolet functionalization.The morphology and hydrophilicity of 3D printed Ti6Al4V specimens before and after surface modification were analyzed by scanning electron microscopy and contact angle test.RESULTS AND CONCLUSION:(1)The finite element analysis results showed that under the vertical average bite force,the Gyroid structure could uniformly disperse the load acting on the implant into the entire structure.The load on the solid structure implant could only be dispersed on its outer surface and concentrated in the neck.The maximum equivalent stress of the Gyroid structure implant was 200.67 MPa,which did not exceed 50%of the yield strength of Ti6Al4V material.The maximum equivalent stress of the Gyroid structure implant on the surrounding bone tissue was 24.27 MPa,which was slightly higher than the maximum equivalent stress of the solid structure implant 17.32 MPa,and in the range of 20-60 MPa.The stimulation effect of the Gyroid structure implant on new bone formation was better than that of the solid structure implant.(2)The 3D printing technology could materialize the Gyroid structure implant model.Scanning electron microscopy showed that there were many unmelted spherical metal particles on the surface of the 3D printed Ti6Al4V specimens.After sandblasting and acid etching,a micron-scale mesh pore structure was formed on the surface,and no protruding metal particles were seen.The surface morphology of the superimposed UV functional treatment group was basically consistent with that after sandblasting and acid etching.The contact angle test results showed that the surface hydrophilicity of the specimens treated with ultraviolet functionalization plus sandblasting and acid etching was better than that of the sandblasting and acid etching and non-surface treatment groups.(3)The sandblasting and acid etching technology can remove the weakly connected metal particles on the 3D printed specimen and improve the similarity between the solid model and the design model.On this basis,the ultraviolet functionalization treatment can significantly improve the hydrophilicity of the 3D printed Gyroid structure implant surface without affecting its structure.

BACKGROUND:Porous structures based on triple periodic minimal surfaces are one of the most promising orthopedic biostructures,among which the Gyroid structure is characterized by high specific surface area,high permeability,and zero mean curvature.OBJECTIVE:To screen the wall thickness interval of TC4 bionic bone scaffolds with 4 mm single-cell Gyroid structure matching the elastic modulus range of cancellous bone of the mandible through finite element analysis combined with mechanical compression test testing.METHODS:The finite element model of the 4 mm single-cell Gyroid structure with different wall thickths(0.1,0.2,0.3,0.4,0.5,0.6,0.7,and 0.8 mm)was established.The equivalent elastic modulus of the Gyroid structure was analyzed,and the wall thickness interval of the Gyroid structure matching the elastic modulus range of the maxillary resinous bone was selected with different wall thicknesses of 0.2,0.3,0.4,0.5,0.6,and 0.7 mm,respectively.According to finite element analysis screening results,the material selected was Ti6Al4V.Selective laser melting was used to prepare 3D printed Gyroid structure specimens.The surface treatment was carried out by large-grained sand blasting and acid etching.The elastic modulus and compressive strength of the specimen were tested by mechanical compression experiment.RESULTS AND CONCLUSION:(1)The finite element analysis results showed that the equivalent elastic modulus of the Gyroid structure increased with the increase of wall thickness,and the equivalent elastic modulus of the Gyroid structure with wall thickness of 0.2-0.7 mm was within the range of the elastic modulus of the spongy bone of the mandible(1.5-4.0 GPa),which was used for 3D printing of the Gyroid structure specimen.(2)The mechanical compression test results showed that the elastic modulus and compressive strength of the Gyroid structural specimen increased with the increase of wall thickness,and the elastic modulus of the Gyroid structural specimen with wall thickness of 0.3-0.5 mm was within the range of the elastic modulus of the cancellous bone of the mandible.The compressive strength of the Gyroid specimen with 0.3-0.7 mm wall thickness was consistent with the mechanical properties of the mandible.(3)The results show that the Gyroid structure of 0.3-0.5 mm wall thickness is compatible with the range of elastic modulus of the mandible.

Objective:To summarize the tools and applications of functionality appreciation assessment.Methods:A computerized search was conducted in PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc for literature related to functionality appreciation assessment tools and their applications, with the time frame from database inception to May 12, 2024.Results:A total of 26 articles were included. Functionality appreciation was found to be associated with demographic, physiological, psychological, and social health factors. Functionality appreciation assessment tools demonstrated good psychometric properties across different cultural backgrounds and populations.Conclusions:Functionality appreciation exerts multidimensional benefits on physical and psychological health. However, the available functionality appreciation assessment tools are limited in variety. Future research should further explore the applicability of these tools in different populations in China.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.